Patent application title: Isolated aquaporin in its closed conformation
Inventors:
Per Kjellbom (Lund, SE)
Kristina Hedfalk (Goteborg, SE)
Susanna Törnroth (Goteborg, SE)
Maria Ekerot (Lund, SE)
Urban Johansson (Lund, SE)
Richard Neutze (Vastra Frolunda, SE)
Assignees:
Hydrogene Lund AB
IPC8 Class: AG06G758FI
USPC Class:
703 11
Class name: Data processing: structural design, modeling, simulation, and emulation simulating nonelectrical device or system biological or biochemical
Publication date: 2011-08-11
Patent application number: 20110196662
Abstract:
The invention relates to an isolated aquaporin having a bound ligand,
wherein said ligand close the conformation of said aquaporin and inhibit
and/or reduce water transport of said aquaporin, and/or a high resolution
structure of an isolated aquaporin in a closed conformation characterised
by the coordinates deposited at the Protein Data Bank ID:1Z98, a crystal
of said isolated aquaporin as well as the coordinates defining said
crystal and the use of said aquaporin, and the use of the high-resolution
structure as defined by the coordinates deposited at PDB ID:1Z98, and a
method to produce said aquaporin.Claims:
1. A method of creating a model of a closed aquaporin of unknown
3-dimensional (3D) structure, the method comprising: replacing one or
more amino acids of a an atomic structure of a closed aquaporin of known
3D structure, wherein said atomic structure of a closed aquaporin of
known 3D structure comprises the atomic coordinates set forth in Appendix
1, with a corresponding amino acid of the closed aquaporin of unknown 3D
structure; and producing a model of the 3D structure of the closed
aquaporin of unknown 3D structure.
2. The method according to claim 1, wherein said closed aquaporin of unknown 3D structure is a mammalian aquaporin.
3. An in-silico method of creating a homology model of a closed aquaporin of unknown structure, the method comprising: computationally mutating at least one of the amino acid residues in a high resolution structure of a spinach aquaporin denoted SoPIP2;1 characterized by the atomic coordinates set forth in Appendix 1 into the corresponding amino acid residue of said aquaporin of unknown structure; producing said homology model of said aquaporin of unknown structure; and optionally computationally refining said homology model.
4. The method according to claim 3, wherein said closed aquaporin of unknown structure is a mammalian aquaporin.
5. An in-silico method of creating a homology model of a closed aquaporin of unknown structure, the method comprising: computationally mutating at least one of the amino acid residues in a high resolution structure of a crystalline, isolated, closed aquaporin of SEQ ID NO:33, wherein said aquaporin is a spinach aquaporin denoted SoPIP2;1 and comprises a bound cadmium ion; the crystal being in space I4 and having unit cell dimensions a, b, c (Å) 90.0, 90.0, 188.9 and α, β, γ (°) 90.0, 90.0, 90.0, into the corresponding amino acid residue of said aquaporin of unknown structure; producing said homology model of said aquaporin of unknown structure; and optionally computationally refining said homology model.
6. The method according to claim 4, wherein said closed aquaporin of SEQ ID NO:33 is a crystal of an aquaporin having a high resolution structure characterized by the atomic coordinates set forth in Appendix 1.
7. The method according to claim 4, wherein said closed aquaporin of unknown structure is a mammalian aquaporin.
Description:
[0001] This application is a Divisional of U.S. Ser. No. 12/066,152, filed
15 May 2009, which is a National Stage Application of PCT/SE2006/001036,
filed 8 Sep. 2006, which claims benefit of Serial No. 0501999-7, filed 9
Sep. 2005 in Sweden and which applications are incorporated herein by
reference. To the extent appropriate, a claim of priority is made to each
of the above disclosed applications.
FIELD OF INVENTION
[0002] The invention relates to an isolated aquaporin having a bound ligand, wherein said ligand closes the conformation of said aquaporin and inhibit and/or reduce water transport of said aquaporin, and/or a high resolution structure of an isolated aquaporin in a closed conformation characterised by the coordinates set forth in Appendix 1, a crystal of said isolated aquaporin as well as the coordinates defining said crystal and the use of said aquaporin, the use of the high-resolution structure as defined by the coordinates set forth in Appendix 1, and a method to produce said aquaporin.
BACKGROUND OF INVENTION
[0003] Water is the medium of life. Since biological membranes have only limited intrinsic water permeability cells maintain the flux of water into and out of the cell via a family of water-specific, membrane protein channels called aquaporins (1). Members of the aquaporin family are found in archea, eubacteria and eukaryotes, including fungi, animals and plants. They serve an astonishing variety of physiological functions (5-7) and are easily identified by sequence similarity across all kingdoms of life. In higher eukaryotes, water transport activity of aquaporins is frequently regulated by phosphorylation, pH and osmolarity (6-8). Aquaporins in plants and animals are highly conserved and form large protein families with 35 members in higher plants (9) and 13 members in humans (5,10).
[0004] Based upon phylogenetic analyses, plant aquaporins are further divided into four subfamilies and their presence in primitive plants such as the bryophyte Physcomitrella patens implies that this specialization was already present in an ancient plant-ancestor (11). There are 13 remarkably conserved plasma membrane aquaporins (Plasma membrane Intrinsic Proteins or PIPs) which are all regulated, and these further separate into two distinct phylogenetic groups (PIP1 and PIP2).
[0005] Closure of the plant aquaporin SoPIP2;1 of spinach (formerly called PM28A(2)) has been reported to be triggered by the dephosphorylation of two serine residues: Ser115 in the cytosolic loop B (conserved as Ser in 12, and as Thr in 1, of the 13 Arabidopsis PIPs) and Ser274 in the C-terminal region (2,3) (conserved as Ser in 7, and as Thr in 1, of the 8 Arabidopsis PIP2s). Both residues are situated in consensus phosphorylation sites. Furthermore, the simultaneous closure of all Arabidopsis PIPs upon anoxia was recently reported to depend upon the protonation of a strictly conserved histidine residue in loop D (4), which corresponds to His193 in SoPIP2;1 (SEQ ID NO: 33). It is an intriguing observation that distinct chemical signals acting on residues well separated in sequence induces an identical physiological response within PIPs. While a number of structures have been reported for water (12-16) and glycerol (17) channels, no plant aquaporin structure has yet been determined at high resolution. Gonen et al. (15) reports a low-resolution structure of AQP0. At this resolution (3 Å) water molecules cannot be seen and the authors are not able to conclude that the structure represents a closed aquaporin. This is also clearly stated by the authors in the article (p 194-195: "We note, however, that our resolution is currently limited to 3 Å, and even if a pore appears to be in a closed conformation, it might still be permeable to solutes."). Furthermore, a high-resolution structure of AQP0 (16) with an open conformation show no global change in the structure as compared to the low-resolution AQP0 structure reported in ref 15. Thus, it is likely that the structure in ref 15 represents an open aquaporin. Recently an additional report (35) arrives at the same conclusion that the structure of AQP0 reported in ref 15, as well as in ref 16, is open and not closed to water transport.
[0006] In addition, the low-resolution structure of AQP0 presented in Gonen et al. (15) is based on a proteolytically cleaved AQP0. Thus, both the N- and C-terminal regions of the protein are cleaved off and can therefore not participate in closing the pore (36). Kukulski et al. (37) depicts a 5 Å low-resolution structure of an aquaporin that in a previous publication by the same authors had been shown to be open (28). However, from a 5 Å low-resolution structure it is impossible to see if the pore is open or closed.
[0007] Furthermore, no gating mechanisms have been unambiguously demonstrated. Therefore it is crucial to establish the atomic structure of an aquaporin in its closed formation. Structural information of the closed conformation is necessary for understanding the mechanism of gating and for structure-based design and development of organic compounds, peptides or antibodies that either stabilize the open conformation or the closed conformation. By obtaining the structure of a closed aquaporin it will for the first time be possible to use that particular structure to modify the gating. This can in plants be done by direct genetic engineering of aquaporins in order to improve stress tolerance, e.g. against drought stress. In mammalian species pharmaceutical compounds that stabilize the closed or the open conformation of aquaporins can be designed based on the closed conformation of the aquaporin SoPIP2;1 (SEQ ID NO: 33) from the plasma membrane of the plant spinach. Such inhibitors and activators are candidate pharmaceutical and cosmeceutical compounds, e.g. antiperspirants. Aquaporins are also important for cell migration during angiogenesis, wound healing, tumour spread and organ regeneration (27), processes that therefore can be modulated by pharmaceutical compounds interacting and modifying the gating of aquaporins. Dysfunction of human aquaporins is associated with clinically important diseases such as polyuria in kidney diseases. Conversely, increased water retention is associated with congestive heart failure, liver cirrhosis and nephritic syndrome. Also pathological skin conditions such as anhidrosis, hyperhidrosis and conditions where the transepidermal water loss is deviating from normal conditions could be targets for aquaporin inhibitors and activators. Moreover, brain edema, glaucoma and skin burns could be treated by inhibitors and activators of aquaporins. The cosmeceutical applications of aquaporin inhibitors and activators include not only antiperspirant but also dermatological conditions where one wants to influence the transepidermal water loss. The atomic structure of the closed conformation of SoPIP2;1 (SEQ ID NO: 33) can also be used for designing novel in silico and in vitro screening systems for pharmaceuticals and cosmeceuticals acting as modulators of aquaporin gating and function. Knowledge of the atomic structure of the closed conformation can also be used to design, and also to screen for, peptides and antibodies that interact with certain epitopes on aquaporins and thus effect activity and gating.
SUMMARY OF THE INVENTION
[0008] The object of the present invention is to solve the above, discussed problems in connection with aquaporins and the gating mechanism of aquaporins. This object is achieved by the present invention as specified below.
[0009] The object of the present invention, is the isolation and determination of the structure of an aquaporin and thereby enable the possibility to solve all the above mentioned problems.
[0010] The invention relates in one aspect to an isolated aquaporin having a bound ligand, wherein said ligand closes the conformation of said aquaporin and inhibit and/or reduce water transport of said aquaporin, and/or a high resolution structure of an isolated aquaporin in a closed conformation characterised by the coordinates set forth in Appendix 1, a crystal of said isolated aquaporin as well as the coordinates defining said crystal and the use of said aquaporin, the use of the high-resolution structure as defined by the coordinates set forth in Appendix 1, and a method to produce said aquaporin.
[0011] In a second aspect, the invention relates to a crystal of an isolated aquaporin in its closed conformation having an atomic structure characterised by the coordinates set forth in Appendix 1.
[0012] In a third aspect the invention relates to a method of producing an isolated aquaporin having a closed conformation comprising the steps; providing said aquaporin, adding a ligand to said aquaporin; producing crystals and obtaining an aquaporin having a ligand bound to said aquaporin, wherein said ligand closes the conformation of said aquaporin and inhibit and/or reduce water transport through said aquaporin.
[0013] In a fourth aspect the invention relates to the use of said isolated aquaporins or said crystal of said aquaporin as well as the coordinates characterising said crystal.
[0014] In a final aspect the invention relates to the use of a ligand binding to the cytoplasmic side to close the conformation of an aquaporin.
[0015] Further advantages and objects with the present invention will be described in more detail, inter alia with reference to the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
[0017] FIG. 1 shows sequence comparisons between selected aquaporins. Sequence comparisons between selected aquaporins from plants, animals and bacteria. SoPIP2;1 (SEQ ID NO: 33) is indicated with an arrow and important conserved residues among PIPs or PIP2s are indicated at the top together with the number of the corresponding residue in SoPIP2;1 (SEQ ID NO: 33). At, Arabidopsis thaliana, SEQ ID NO: 9, see also SEQ ID NOs: 10-13, 23-30, 53-55, 58-60, 64, 65, 68, 73-77, 81-85, 87, 88, and 91; Zm, Zea mays, SEQ ID NO: 3, see also SEQ ID NOs: 4-8, 16-22, 56, 57, 61-63, 66, 67, 69-72, 78-80, 86, 89, and 90; Pa, Picea abies, SEQ ID NO: 14, see also SEQ ID NO: 31; Pp, Physcomitrella patens, SEQ ID NOs: 15, see also SEQ ID NO: 32; So, Spinacea oleracae, SEQ ID NO: 33; Hs, Homo sapiens, SEQ ID NO: 34, see also SEQ ID NOs: 40-44, 46, 47, 49-52; Bt, Bos taurus, SEQ ID NO: 35, see also SEQ ID NO: 38; Gg, Gallus gallus, SEQ ID NO: 36, see also SEQ ID NO: 39; Xl, Xenopus leavis, SEQ ID NO: 37; Ec, Escherichia coli, SEQ ID NO: 45, see also SEQ ID NO: 48.
[0018] FIG. 2 shows structure of SoPIP2;1 (SEQ ID NO: 33) tetramer. SoPIP2;1 (SEQ ID NO: 33) tetramer viewed from the extracellular side (a) and two of the monomers viewed from the inside of the tetramer (b). The oxygens of water molecules and the Cd2+ ion are indicated as spheres.
[0019] FIG. 3 shows structural comparisons of eukaryotic aquaporins. Overlay of AQP0, AQP1 and SoPIP2;1 (SEQ ID NO: 33). The D-loop with His193 and Leu 197 (SEQ ID NO: 33) is blocking the pore in SoPIP2;1 whereas the D-loops of AQP0 and AQP1 are occupying the same space as the C-terminal region in SoPIP2;1 ending with Ser274 (SEQ ID NO: 33). The Cd2+ ion is indicated by the sphere at the lower left side of the figure.
[0020] FIG. 4 shows representation of the closed conformation of SoPIP2;1 (SEQ ID NO: 33). Representation of the closed conformation of SoPIP2;1 (SEQ ID NO: 33). a, The pore diameter of the closed conformation of SoPIP2;1 (SEQ ID NO: 33) calculated using HOLE represented as a funnel with dots illustrating the pore boundaries. b, A close up view of the pore near the gating region of loop D characterized by Leu197, Pro195 and Val194 (SEQ ID NO: 33).
[0021] FIG. 5 shows electron density at the sites of regulation of SoPIP2;1 (SEQ ID NO: 33) by phosphorylation and pH. Electron density at the sites of regulation by phosphorylation and pH for SoPIP2;1 (SEQ ID NO: 33). a, Close up view of the divalent cation binding site showing the location of the Cd2+ ion and the network of H-bonds linking Gly30 and Glu31 via Arg118 to Arg190 and Asp191 (SEQ ID NO: 33) of loop D. b, Close up view of the phosphorylation residue Ser115 illustrating its H-bond to Glu31 (SEQ ID NO: 33). c, Close up view of His193 (SEQ ID NO: 33). When protonated an alternate conformation for His 193 may be adopted which forms a salt bridge to Asp28 (SEQ ID NO: 33). d, Electron density for Ser274 which contacts Pro199 and Leu200 (SEQ ID NO: 33) of a neighboring monomer of the SoPIP2;1 (SEQ ID NO: 33) tetramer. All 2F.sup.obs--Fcalc maps are contoured at 1.0σ.
[0022] FIG. 6 shows difference anomalous density map for Cd2+ ion. Difference anomalous density map illustrating the location of a single metal. a, Long distance view of the map. b, Close up view of the map near the assigned Cd2+ binding site. This map is contoured at 5σ.
DETAILED DESCRIPTION OF THE INVENTION
Definitions
[0023] In the context of the present application and invention, the following definitions apply:
[0024] The term "pore diameter" is intended to mean the diameter at different positions within the pore of the aquaporin.
[0025] The term "closed conformation" refers to the structure of a closed aquaporin that do not permit the transfer of water molecules from one side of the water channel to the other side due to a too small pore diameter to allow water to pass
[0026] The term "aquaporin" is intended to mean a membrane channel protein that facilitate the flux of water and/or other small solutes across biological membranes.
[0027] The term "gating mechanism" refers to the way the overall structure and the positions of the individual amino acids change when the aquaporin goes from an open to a closed conformation or visa versa.
[0028] The term "ligand" is intended to mean any molecule (or part of a molecule) that is bound or is able to bind selectively and stoichiometrically to one or more specific sites on another molecule, for example a protein. Examples of ligands are peptides, small molecules, Cd2+, Ca2+, Mg2+, Mn2+ or any other divalent cation.
[0029] The synonymous terms "high resolution" and "atomic resolution" are intended to mean the minimum distance two atoms can be separated from each other and still be seen as two atoms and being below 2.5 Å.
[0030] The term "D-loop" is intended to mean at least a stretch of amino acid residues being between the fourth and the fifth membrane spanning region of an aquaporin, in SoPIP2;1 represented by amino acid residues 182-201 (see, e.g., SEQ ID NO: 33), as shown in FIG. 1.
[0031] The term "homology modelling" is intended to mean a computational method for determining the structure of a protein based on its similarity to known structures. Given the amino acid sequence of an unknown structure and the solved structure of a homologous protein, each amino acid in the solved structure is mutated, computationally, into the corresponding amino acid from the unknown structure. The accuracy of structures determined by homology modelling depends largely on the degree of similarity between the unknown and the known protein sequence.
[0032] The term "atomic coordinates" or "structure coordinates" is intended to mean mathematical coordinates that describe the positions of atoms in crystals of the aquaporin.
[0033] The diffraction data obtained from the crystals are used to calculate an electron density map of the repeating unit of the crystal. The electron density maps are used to establish the positions (i.e. coordinates X, Y, and Z) of the individual atoms within a single aquaporin. Those of skill in the art understand that a set of structure coordinates determined by X-ray crystallography is not without standard error. For the purpose of this invention, any set of structure coordinates for an aquaporin from any source has a root mean square deviation of non-hydrogen atoms of less than 0.75 Å when superimposed on the non-hydrogen atom positions of the said atomic coordinates (Berman et al., 2000, Nucleic Acids Research, 28, 235-242) set forth in Appendix 1. Other examples of aquaporin structures are 1TM8, 1YMG, 1J4N, 1RC2 and 1FX8.
[0034] In the list of atomic coordinates set forth in Appendix 1 the term "atomic coordinate" refers to the measured position of an atom in the structure in Protein Data Bank (PDB) format, including X, Y, Z and B for each. The assembly of "atomic coordinate" also refers to "atomic coordinates" or "structure coordinates". The term "atom type" refers to the element whose coordinates are measured. The first letter in the column defines the element. The term "X,Y,Z" refers to the crystallographically defined atomic position of the element measured with respect to the chosen crystallographic origin. The term "B" refers to a thermal factor that measures the mean variation of an atom's position with respect to its average position.
[0035] The term "molecular modelling" or "molecular structural technique" is intended to mean the use of computers to draw realistic models of what molecules look like and to make predictions about structure activity relationships of ligands and other agents. The methods used in molecular modelling range from molecular graphics to computational chemistry.
[0036] The term "molecular dynamics simulations" is intended to mean computer simulations of the dynamic properties of a molecule such as conformational changes using e.g. the Gromacs simulation suite or VMD (Ref. Berendsen H. J. C., van der Spoel, D. and van Drunen, R., Comp Phys Commun 91, 43 (1995) and Humphrey, W., Dalke, A. & Schulten, K. VDM: visual molecular dynamics. J Mol Graph 14, 33-8 (1996).)
[0037] The terms "bind", "binding", "bond", "bonded", when used in reference to the association of "binding agents" such as atoms, molecules, chemical groups or ligands is intended to mean any physical contact or association of two or more atoms, molecules, or chemical groups (e.g., the binding of a ligand with a protein subunit refers to the physical contact between the ligand and the protein subunit). Such contacts and associations include covalent and non-covalent types of interactions.
An Aquaporin
[0038] In a first aspect, the invention relates to an isolated aquaporin having a bound ligand, wherein said ligand close the conformation of said aquaporin and inhibit and/or reduce water transport of said aquaporin, and/or a high resolution structure of an isolated aquaporin in a closed conformation characterised by the coordinates set forth in Appendix 1. Examples of other aquaporins are those listed in FIG. 1, such as AQP0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (see, e.g., SEQ ID NOs: 34-44, 46, and 47) or SoPIP2:1 (SEQ ID NO: 33). Said ligand may be a ligand as defined above. Examples of ligands are Cd2+, Ca2+, Mg2+, Mn2+ or any other divalent cation. The ligand may be bound at different sites on the aquaporin, such as at the cytoplasmic side. The ligand may for example be a non-covalently bound ligand. The ligand bound closed conformation can be defined by a structure at high resolution. By determination of the structure of an isolated and crystallized aquaporin, a closed aquaporin conformation was obtained for the first time at atomic resolution. This enabled the possibility to deduce the gating mechanism of an aquaporin for the first time. The structure of such a closed aquaporin will enable the possibility to design new pharmaceutical (e.g., diuretics and inhibitors of angiogenesis) and cosmeceutical (e.g., antiperspirants) compounds that either stabilize the closed conformation or the open conformation. Since aquaporins are evolutionary very well conserved all the way from bacteria to plants and mammals, such compounds can be effective on aquaporins in many or all species. The atomic structure of a closed aquaporin such as SoPIP2;1 (SEQ ID NO: 33) can also be used for structure based drug design and also for designing screening methods, both in silico and in vitro, for identifying inhibitors and activators of aquaporins. By obtaining the structure of a closed aquaporin and then using that particular structure it will be possible by genetic engineering to modify the gating and functioning of plant aquaporins, and to generate new plant varieties with improved stress tolerance against drought.
[0039] Furthermore, the invention relates to an aquaporin having a pore diameter of around 2.1 Å at the constriction region and less than that in the pore towards the cytosolic vestibule when the aquaporin is closed. The pore diameter is defined by the boundaries of the water conducting pore. The pore diameter may be measured by the use of a program such as the HOLE program described by Smart et al., Biophys J 65, 2455-2460 (1993). The structure was determined using a crystallised form of an aquaporin wherein the aquaporin prior to crystallisation was produced in Pichia pastoris, i.e., overproduction of a heterologous eukaryotic protein as described below under the Examples. The structure was solved at 2.1 Å resolution.
[0040] Additionally the aquaporin may be eukaryotic, such as selected from the group consisting of human, plant or animal aquaporins. Examples of plant species are spinach, sugar beet, Arabidopsis, maize, rice, wheat, barley, oats and mammalian species are human, bovine, sheep and other mammals, along with non-eukaryotic organisms such as yeast or bacteria. One specific example being the aquaporin from the plant spinach (SoPIP2;1, SEQ ID NO: 33), the present invention, was crystallised as a tetramer displaying extended hydrophobic interactions between monomers as shown in FIG. 2. By the use of the X-ray crystal structure of SoPIP2;1 (SEQ ID NO: 33) and then overlay the X-ray structure with the structure of another aquaporins, such as the bovine AQP0 (16) (SEQ ID NO: 35) and AQP1(13) (SEQ ID NO: 38) it was possible to identify that they had an identical structural core consistent with the "hour-glass model" (19), differing only by 0.8 Å r.m.s.d. on Cα atoms within the transmembrane regions (FIG. 3). SoPIP2;1 (SEQ ID NO: 33), bovine AQP0 (16) (SEQ ID NO: 35) and AQP1 (13) (SEQ ID NO: 38). Likewise, the half-helices formed by loops B (cytosolic) and E (extracellular), with the Asn-Pro-Ala aquaporin signature motif at the N terminal ends, fold into the channel from opposite sides of the membrane and together create a seventh transmembrane region, which is perfectly preserved structurally. Seven water molecules are observed within the SoPIP2;1 (SEQ ID NO: 33) channel (FIG. 3), revealing an unbroken water network stretching almost fully through the pore with a maximum distance of only 3.1 Å between each water. The D-loop of the aquaporin or parts thereof being involved in the closed conformation of the aquaporin. The D-loop or part thereof being involved in the gating mechanism like a door which opens and closes. A key residue in this respect is the fully conserved Leu197 (SEQ ID NO: 33) of loop D in SoPIP2;1, which inserts into a cavity near the entrance of the channel and, in combination with His99, Val104 and Leu108 (FIG. 4b, SEQ ID NO: 33), creates a hydrophobic barrier blocking the pore. Calculations of the channel width, using HOLE (23) establish that the pore narrows to a diameter of approximately 1.4 Å at Leu197 and narrows further to 0.8 A near Pro195 and Val194 (FIG. 4, SEQ ID NO: 33). This compares with the minimum pore diameter of 2.1 Å within the SoPIP2;1 (SEQ ID NO: 33) constriction region (9) and is insufficient to allow the passage of water. Loop D and Leu197 (SEQ ID NO: 33) are also key to understanding the molecular mechanism of channel opening or closure in response to specific biochemical signals. In FIGS. 4b and c two water molecules separated by 6.4 Å are visible on either side of the hydrophobic barrier associated with Leu197, and one of these forms H-bonds to His99 and the main-chain oxygen of Pro195 (SEQ ID NO: 33). Should a conformational change in loop D concomitantly displace Leu197, Pro195 and Val194 (SEQ ID NO: 33), then a pathway between these two water molecules extending into the cytosol would open. Analogy with the 2.1 Å pore-diameter of the constriction region implies that a displacement of these loop D residues by as little as 1.3 Å could be sufficient to open the channel. It has been postulated that divalent cations may play a role in aquaporin regulation (1,2,21) and inhibition (24,25). In FIGS. 2 and 3 a heavy-metal (FIG. 6 shows the anomalous difference density map) is observed near loop D and is assigned as Cd2+ since the addition of this ion improved the crystal quality. Cd2+ may be replaced by another divalent cation in vivo, and a search for similar structural motifs (26) revealed 13 PDB entries containing Ca2. As such, we postulate that this metal binding site likely binds Ca2 in vivo. This site is implicated in regulation since it serves to anchor loop D, through a network involving ionic interactions and H-bonds (FIG. 5a), onto a short α-helix of the N-terminus (FIG. 3) and thus appears to be critical for defining the unique conformation of loop D observed for SoPIP2;1 (SEQ ID NO: 33). Specifically, Arg190 and Asp191 of loop D are connected to the side-chain of Arg118 (strictly conserved in PIPs) and Gly30 via a H-bond network containing three water molecules (SEQ ID NO: 33). Arg118 in turn forms H-bonds to Glu31 (strictly conserved in PIPs) which ligates the Cd2+ ion (FIG. 5a, SEQ ID NO: 33). Significantly, the hydroxyl group of the conserved phosphorylation site Ser115 also forms a H-bond to Glu31 (FIG. 5b, SEQ ID NO: 33). It is therefore apparent that the covalent attachment of a phosphate group onto the hydroxyl oxygen of Ser115 would significantly perturb the conformation of Glu31, which would result in disrupting the crucial water mediated H-bond network from Arg118 to Arg190 and Asp191 (FIG. 5a, SEQ ID NO: 33). We suggest that the disruption of this anchoring network would profoundly alter the conformation of loop D, and the resulting structural change would be sufficient to displace Leu197, Pro195 and Val194 (SEQ ID NO: 33) and thereby unplug the entrance into the aquaporin channel from the cytosol. It is even possible that this displacement may result in loop D adopting a conformation somewhat closer to that of AQP0 and AQP1 (FIG. 3).
[0041] Conversely, when Ser115 is phosphorylated and the water channel is open, the protonation of His193 (SEQ ID NO: 33) (strictly conserved) closes the channel (4). A mechanism for pH-regulated PIP gating also emerges from the structure of SoPIP2;1 (SEQ ID NO: 33). In FIG. 5c the conformation of His193 (SEQ ID NO: 33) is shown. At low pH where His193 is protonated, a simple rotation of the histidine side-chain (FIG. 5c) would enable it to form a salt bridge to Asp28 (SEQ ID NO: 33) (conserved in PIPs as either Asp or Glu). In this manner the H-bond mediated anchor for loop D onto the N-terminus (FIG. 5a), which we suggest is lost upon Ser115 (SEQ ID NO: 33) phosphorylation, would be recovered. As such the structure of Ser115 (SEQ ID NO: 33) phosphorylated SoPIP2;1 at low pH can be expected to be similar to that reported here, with the cytosolic side of the aquaporin being capped by loop D and Leu197, Pro195 and Val194 (SEQ ID NO: 33) effectively blocking the water channel.
[0042] A structural framework for aquaporin regulation may also be proposed when considering the phosphorylation of Ser274 (SEQ ID NO: 33) (conserved in PIP2 homologues). In this case, however, Ser274 (SEQ ID NO: 33) is distant from the Cd2+ site. Instead, Ser274 (SEQ ID NO: 33) is located in the C-terminal region, of SoPIP2;1 which extends towards the four-fold axis of the tetramer and interacts with the main-chain nitrogen of Pro199 (SEQ ID NO: 33) of an adjacent monomer (FIGS. 2b, 5d), which is the final residue of loop D. Should Ser274 (SEQ ID NO: 33) become phosphorylated then this interaction would be profoundly affected, and the creation of a cluster of four negative phosphate charges in close proximity should induce a significant conformational change in the C-terminal region. An interaction between Ser274 (SEQ ID NO: 33) of one monomer with residues in loop D of another monomer in the aquaporin tetramer also suggests an orchestrated regulation of the monomers within homotetramers.
[0043] The closed conformation of SoPIP2;1 (SEQ ID NO: 33) was crucial for discerning a gating mechanism and the positions of specific amino acids in the closed conformation, that previously biochemical and genetic experiments had identified as important for gating, immediately suggest how the closed structure can be stabilized and destabilized.
[0044] According to a second aspect, the invention relates to an aquaporin comprising an atomic structure characterised by the coordinates set forth in Appendix 1 and to phases computed from the coordinates of said atomic structure. A person skilled in the art can easily by the use of the coordinates set forth in Appendix 1 in combination with one or more molecular structural technique, develop new aquaporins or binding agents such as inhibitors to aquaporins as well as modify the inhibitors.
[0045] The disclosed isolated aquaporin crystal structure of said aquaporin as well as the coordinates characterising said crystal may be used to screen for binding agents, or ligands, that stabilise and/or destabilise the closed conformation of said aquaporin or to create homology models of closed aquaporins. Other uses are to identify binding agents (ligands) or identification of at least one genetic modification capable of affecting the gating mechanism of said aquaporin, such as by an in silico technique. Another use is the development of genetically modified plants, such as agricultural plants.
[0046] Accordingly, water channels are functionally characterized by heterologous overexpression in Xenopus laevis oocytes. The method is described in detail in references 1 and 2. The oocytes have low intrinsic water permeability, allowing detection of any increase in water permeability due to the expressed aquaporin. In this system AQP1, 2, 3, 4, 5, 7, 8, 9 and 10 (see, e.g., SEQ ID NOs: 38-42 and 44) have high water permeabilities compared to AQP0, 6 and 11 (see, e.g., SEQ ID NOs: 34-37, 43, and 46) that are considered as poor water channels (Table 1; see also table 1 in Castle N A, Drug Discov. Today. 2005, 10, 485-93). AQPs with a high water permeability are primary targets for binding agents, ligands, that stabilize and/or destabilize a closed conformation since only a minor or no effect is expected by modulation of a poor or non-functional water channel.
TABLE-US-00001 TABLE 1 Water permeabilities for mammalian aquaporins and SoPIP2;1 (SEQ ID NO: 33) Water Pf-values permeabilitya (μm/s)b Referencec AQP0 Low 13 ± 2 38 (see, e.g., SEQ ID NOs: 34-37) AQP1 High 190 ± 20 38 (see, e.g., SEQ ID NOs: 38 and 39) AQP2 High 100 ± 10 38 (see, e.g., SEQ ID NO: 40) AQP3 High 80 ± 20 38 AQP4 High 290 ± 10 38 (see, e.g., SEQ ID NO: 41) AQP5 High 100 ± 10 38 (see, e.g., SEQ ID NO: 42) AQP6 Low 7.4 ± 0.7 39 (see, e.g., SEQ ID NO: 43) AQP7 High 150 40 AQP8 High 205 ± 12 41 (see, e.g., SEQ ID NO: 44) AQP9 High 289 ± 66 42 AQP10 High 87 43 AQP11 Low 15 ± 6 44 (see, e.g., SEQ ID NO: 46) AQP12 NKc NK (see, e.g., SEQ ID NO: 47) SoPIP2;1 (SEQ ID NO: 33) High 110 2 aWater permeabilites were categorized as either high or low based on Pf-values, using a cut off value of 50 μm/s. bOsmotic water permeability (Pf-values, average ± SD) were determined by heterologous overexpression in Xenopus laevis oocytes. 5 to 50 ng of cRNA encoding an aquaporin were injected. After a preincubation to allow protein expression, oocytes were transferred to hypotonic media and the swelling rates were recorded and used to calculate the Pf-values. cNK, not known
[0047] The invention also relates to a method of how to produce said aquaporin. The method comprises the steps of providing said aquaporin, adding a ligand to said aquaporin, producing crystals and obtaining an aquaporin having a ligand bound to the cytoplasmic side of said aquaporin, wherein said ligand close the conformation of said aquaporin and inhibit and/or reduce water transport through said aquaporin. The method being described in the examples.
[0048] Methods of Using the Isolated Aquaporin
[0049] The invented isolated aquaporin having a closed conformation, wherein said closed conformation is obtained by binding a ligand to said aquaporin as defined above, said crystal as well as said atomic structure may be used in several applications such as to screen for binding agents (ligand) that stabilise and/or destabilise the closed conformation of said aquaporin or to create homology models of closed aquaporins based on the closed structure as defined by the coordinates set forth in Appendix 1, to create molecular dynamics simulations of such homology models of eukaryotic or prokaryotic aquaporins, to identify binding agents or identification of at least one genetic modification capable of affecting the gating mechanism of said aquaporin, such as by an in silico technique or to develop genetically modified plants, such as agricultural plants.
[0050] According to another aspect, the invention relates to a method of obtaining a binding agent (ligand) comprising: attaching a number of aquaporins or parts thereof being defined above to a solid support and obtaining an array; adding a number of agents to said array; allowing said agents to bind to said aquaporins or parts thereof; removing said agents which have not bound to said aquaporin or parts thereof and identifying and obtaining said agents which have bound to said aquaporins or parts thereof. In certain aspects one or more steps may be used such as attaching a number of aquaporins having a open conformation and then performing the same steps as with the aquaporins with a closed conformation. By adding such steps it is possible to discriminate between agents, which binds to the aquaporins having a closed conformation from those binding to the aquaporins having an open conformation. The most commonly used assay being a High Throughput Assays. The power of high throughput screening is utilized to test new compounds, which are identified or designed for their ability to interact with an aquaporin of the invention. (For general information on high-throughput screening see, for example, Devlin, 1998, High Throughput Screening, Marcel Dekker; U.S. Pat. No. 5,763,263). High throughput assays commonly use one or more different assay techniques including, but not limited to, those described below. Said solid support may be any solid support such as a column, an array, a membrane, a sandwich assay, competitive or competition assay, latex agglutination assay, homogeneous assay, micro-titre plate format and the micro-particle based assay.
[0051] The aquaporin may be bound to the support by for instance covalent attachment, hydrophobic interactions and/or ionic interactions. The number of agents may be a mixture of different agents, natural, synthetic, semisynthetic or a mixture thereof and organic compounds. After the agents have had the opportunity to bind to the aquaporin, the unbound agents are removed by for example washing by the use of a water solution of buffers such as TRIS, PBS or MOPS. After removal of the unbound agents, the bound agents are to be identified which may be performed by for example NMR, MS and antibodies, such as monoclonal antibodies. The antibodies can be labelled in various ways, including: enzyme-linked immunosorbent assay (ELISA); radioimmuno assay (RIA); fluorescent immunoassay (FIA); chemiluminescent immunoassay (CLIA); and labeling the antibody with colloidal gold particles (immunogold).
[0052] According to a further aspect, the invention relates to a method of obtaining an aquaporin binding agent comprising: using the atomic coordinates as defined above and at least one molecular structural technique to determine which agents interacts with an aquaporin and identifying and obtaining said aquaporin binding agent. Such a method may also contain one or more additional steps, such as those mentioned above in which open aquaporins are used in the same way as the aquaporins having a closed conformation to discriminate between agents which binds one or both of the different types of aquaporins. For basic information on molecular modelling, see, for example, M. Schlecht, Molecular Modelling on the PC, 1998, John Wiley & Sons; Gans et al., Fundamental Principals of Molecular Modelling, 1996, Plenum Pub. Corp.; N.C. Cohen (editor), Guidebook on Molecular Modelling in Drug Design, 1996, Academic Press; and W. B. Smith, Introduction to Theoretical Organic Chemistry and Molecular Modelling, 1996. The molecular structural technique may be one of MOSFLM, SCALA, MOLREP, REFMAC5, NCSREF and CNS.
[0053] According to a further aspect, the invention relates to a method of obtaining a modified agent comprising: using the atomic coordinates as defined above and at least one molecular modelling technique to determine how to modify the interaction of an agent with an aquaporin; modifying said agent based on the determination obtained in step (a) and producing and obtaining a modified agent. The modifications of the agent may be addition, elimination, modification or substitution of functional groups. There are several softwares that may be used and they include as follows; GRID (Goodford, P. J., "A Computational Procedure for Determining Energetically Favourable Binding Sites on Biologically Important Macromolecules" J. Med. Chem., 28, pp. 849-857 (1985)).
[0054] The use of software such as GRID, a program that determines probable interaction sites between probes with various functional group characteristics and the macromolecular surface, is used to analyze the surface sites to determine structures of similar inhibiting proteins or compounds. The GRID calculations, with suitable inhibiting groups on molecules (e.g., protonated primary amines) as the probe, are used to identify potential hotspots around accessible positions at suitable energy contour levels. GRID is available from Oxford University, Oxford, UK.
[0055] MCSS (Miranker, A. and M. Karplus, "Functionality Maps of Binding Sites: A Multiple Copy Simultaneous Search Method." Proteins: Structure, Function and Genetics, 11, pp. 29-34 (1991)). MCSS is available from Molecular Simulations, Burlington, Mass.
[0056] AUTODOCK (Goodsell, D. S. and A. J. Olsen, "Automated Docking of Substrates to Proteins by Simulated Annealing" Proteins: Structure. Function, and Genetics, 8, pp. 195-202 (1990)). AUTODOCK is available from Scripps Research Institute, La Jolla, Calif.
[0057] DOCK (Kuntz, I. D. et al., "A Geometric Approach to Macromolecule-Ligand Interactions" J. Mol. Biol., 161, pp. 269-288 (1982)).
[0058] The program DOCK may be used to analyze an active site or ligand binding site and suggest ligands with complementary steric properties. DOCK is available from University of California, San Francisco, Calif.
[0059] Once suitable chemical entities, compounds, or agents have been selected, they can be assembled into a single ligand or compound or inhibitor or activator. Assembly may proceed by visual inspection of the relationship of the fragments to each other on the three-dimensional image displayed on a computer screen in relation to the atomic coordinates of the aquaporin and/or its complexes with analogues. This would be followed by manual model building using software such as Quanta or Sybyl.
[0060] Useful programs to aid one of skill in the art in connecting the individual chemical entities, compounds, or agents include but are not limited to:
[0061] CAVEAT (Bartlett, P. A. et al, "CAVEAT: A Program to Facilitate the Structure-Derived Design of Biologically Active Molecules". In molecular Recognition in Chemical and Biological Problems", Special Pub., Royal Chem. Soc., 78, pp. 82-196 (1989)).
[0062] Several methodologies for searching three-dimensional databases to test pharmacophore hypotheses and select compounds for screening are available. These include the program CAVEAT (Bacon et al. J. Mol. Biol., 225: 849-858 (1992)) which uses databases of cyclic compounds which can act as "spacers" to connect any number of chemical fragments already positioned in the active site. This allows one skilled in the art to quickly generate hundreds of possible ways to connect the fragments already known or suspected to be necessary for tight binding. CAVEAT is available from the University of California, Berkeley, Calif.
[0063] 3D Database systems such as MACCS-3D (MDL Information Systems, San Leandro, Calif.). This area is reviewed in Martin, Y. C., "3D Database Searching in Drug Design", J. Med. Chem., 35, pp. 2145-2154 (1992).
[0064] HOOK (available from Molecular Simulations, Burlington, Mass.).
[0065] The invented crystal of the aquaporin may be used for several purposes including the methods mentioned above to gain information, which can be used to identify compound as well as modify aquaporins. By obtaining the structure of a closed aquaporin it will be possible to use the knowledge of that particular structure to modify the gating. This can in plants be done by direct genetic engineering of aquaporins in order to improve stress tolerance, e.g. against drought stress. In mammalian species pharmaceutical compounds that stabilize the closed or the open conformation of aquaporins can be designed based on the closed conformation of SoPIP2;1 (SEQ ID NO: 33). Such inhibitors and activators are candidate pharmaceutical and cosmeceutical compounds, e.g. antiperspirants.
[0066] In a final aspect, the invention relates to the use of a ligand to close the conformation of an aquaporin. The ligand to be used being defined and mentioned above.
[0067] Following examples are intended to illustrate, but not to limit, the invention in any manner, shape, or form, either explicitly or implicitly.
EXAMPLES
Example 1
Expression in Pichia pastoris (as Described in Ref 28)
[0068] The SoPIP2;1 (SEQ ID NO: 33) cDNA (GeneBank accession number L77969) was originally amplified using the forward primer EcoRI-YPM28A (5'-CGGAATTCAAAATGTCTAAGGAAGTAAGT-3', SEQ ID NO:1) and the reverse primer PM28A-REV (5'-GAAGATCTTTAATTGGTAGGGTTGCT-3', SEQ ID NO:2). The forward primer has a EcoRI restriction site (underlined) and yeast start codon. The reverse primer has the original stop codon after PM28A and a B gill restriction site (underlined). The PCR product was cloned into pPICZB (Invitrogen) and the resulting plasmid pPM28A-PICZ was sequenced.
[0069] PM28A constructs were transformed into the wild-type P. pastoris strain X-33 (Invitrogen) and transformants with the highest expression according to immunostaining (TetraHis antibodies, Qiagen) were selected and grown on a large scale.
Example 2
Purification of SoPIP2;1 (as Described in Ref 28 and 36)
[0070] The strain was grown in a 3 L fermentor typically resulting in 230 g wet cells/L culture after 24 h of methanol induction. Before breaking, the cells were resuspended in Breaking Buffer (50 mM potassium phosphate, pH 7.5, 5% glycerol), frozen in liquid nitrogen and broken using an X-press. Unbroken cells were collected at 10 000 g, 30 min at 4° C. The 10 000 g supernatant was further centrifuged at 100 000 g, 1.5 h at 4° C. to collect the membrane fraction. Peripheral membrane proteins and proteins adhering to the membranes were removed by urea (4 M urea, 5 mM Tris-HCl, pH 9.5, 2 mM EDTA, 2 mM EGTA)/alkali (20 mM NaOH) treatment. The membrane was washed in each buffer and collected by centrifugation after each wash as described above. SoPIP2;1 (SEQ ID NO: 33) was solubilised in 5% OG (Anatrace) in Buffer A (20 mM HEPES-NaOH, pH 7.0, 50 mM NaCl, 10% glycerol, 2 mM beta-mercapto ethanol) at room temperature for 30 min. Solubilised material was collected at 160 000 g, 30 min at 4° C. Solubilised material was loaded on a Resource S column (20 mM HEPES-NaOH, pH 7.0, 1% OG) followed by a Superdex 200 column (20 mM Tris-HCl, pH 7.5, 100 mM NaCl, 1% OG).
Example 3
Crystallisation
[0071] The purified sample was concentrated using a VivaSpin 20 concentrator (cutoff MW 10 kDa, VivaScience) to a final concentration of 15 mg/ml.
[0072] Crystals were obtained by the hanging drop vapour diffusion technique. 1 μl of sample was mixed 1:1 with the reservoir solution containing 0.1 M Tris-HCl pH 8.0, 30% PEG 400 and 0.1 M NaCl. 0.1 M CdCl2 was added to the drop in a 1:10 ratio.
[0073] The crystallisation setups were left to equilibrate at 4° C. Crystals appeared within a few days and reached the maximum dimension of 0.1 μm within 1 week. Crystals were directly frozen in liquid nitrogen without the need for further cryo-protecting.
[0074] X-ray diffraction data collection: A complete data set to 2.1 Å resolution was collected from a frozen crystal at -80° C. at the Swiss Light Source (SLS) beamline X06SA, Switzerland. Image data were processed using MOSFLM and scaled using SCALA of the CCP4 suite (29). Crystals belong to the space group I4 with 2 molecules in the asymmetric unit. The cell dimensions are a=b=90.0 Å, c=188.9 Å.
[0075] The atomic structure characterised by the coordinates are set forth in Appendix 1.
TABLE-US-00002 TABLE 1 Data collection and refinement statistics Data Collection Space group I4 Cell dimensions a, b, c (Å) 90.0, 90.0, 188.9 α, β, γ(°) 90.0, 90.0, 90.0 *Resolution (Å) 40.0-2.1 (2.27-2.1) *†Rsym 0.098 (0.431) *I/σI 5.0 (1.8) *Completeness (%) 99.8 (99.8) *Redundancy 3.9 (3.2) Refinement *Resolution (Å) 40.0-2.1 (2.27-2.1) No. reflections 41486 .dagger-dbl.Rwork/§Rfree 0.181/0.208 No. atoms Protein 3756 Ligand/ion 2 Water 200 B-factors Protein 29.7 Ligand/ion 30.6 Water 39.6 R.m.s deviations Bond lengths (Å) 0.02 Bond angles (°) 1.540 *Values in parentheses indicate statistics for the highest resolution shell. †Rsym = O|Io - <I> I/O Io × 100%, where Io is the observed intensity of a reflection and <I> is the average intensity obtained from multiple observations of symmetry related reflections. .dagger-dbl.Rwork = O||Fobs| - k|Fcalc||/O|Fobs| × 100%. §Rfree is calculated from 5% of the data which was excluded from refinement.
Example 4
Molecular Replacement & Structural Refinement
[0076] Molecular replacement was carried out using the program MOLREP from the CCCP4i-program suite with the coordinates of bovine AQP1 (PDB entry 1J4N) (SEQ ID NO: 38) as the model. Using two copies of the model in the molecular replacement search, a clear solution with a correlation coefficient and R-factor of 34.3% and 53.1% respectively was found. The crystal packing was checked using the program O(30) and there were no overlaps between molecules. Automated model building was carried out using ARP/WARP(31) and the resulting model was docked to the correct sequence using GUISIDE2. The calculated electron density map at this stage was already of very good quality. Water molecules were picked using ARP/WARP. The model was subjected to multiple rounds of refinement in REFMAC5 (29), NCSREF (29) and CNS (32) with manual rebuilding in O between each round. During refinement, NCS restraints between the two molecules in the asymmetric unit (molecule A and B) were used. The current model contains 251 residues (24-274) and one Cd2+ each for molecule A and B and 200 water molecules. The R-factor and Rfree are 18.1% and 20.8% respectively. The quality of the structure was checked in PROCHECK (33).
[0077] Assignment of Cd2+: A single metal binding site was unambiguously observed as a dominant peak (still visible at 10.0σ) in the anomalous difference density map (FIG. 6) and was identified as a divalent cation due its coordination properties. Since the addition of 0.1 M CdCl2 to crystals improved diffraction from 3.7 Å to 2.1 Å resolution, we further assigned this cation as Cd2+. This assignment was justified by recovering a B-factor of 29.8 Å2 for the Cd2+ after refinement, similar to that of the side chains of its two protein ligands (average B-factor of 27 Å2). A search for similar binding sites using SPASM (34) yielded 13 hits (PDB entries 1BQQ; 1CGE; 1CGL; 1HY7; 1JK3; 1M31; 1MMQ; 1MNC; 1Q3A; 1RM8; 1RMZ; 1ROS; 830C) containing Ca2+ binding sites, and no other metals were found. We therefore make the identification that the Cd2+ binding site is likely to be Ca2+ in vivo.
Example 5
Characterising the Channel
[0078] The package HOLE (23) was used to calculate the pore diameter for SoPIP2;1 (SEQ ID NO: 33), (FIG. 4). With this package a pore diameter of 2.1 Å was recovered at the constriction region, apparently smaller than the effective diameter of water. This paradox is resolved by appreciating that HOLE returns an average diameter assuming a spherical pore, which is an approximation.
REFERENCES
[0079] 1. Preston, G. M., Carroll, T. P., Guggino, W. B. & Agre, P. Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science 256, 385-387 (1992). [0080] 2. Johansson I., Karlsson M., Shukla V. K., Chrispeels M. J., Larsson C. & Kjellbom P. Water transport activity of the plasma membrane aquaporin PM28A is regulated by phosphorylation. Plant Cell 10, 451-459 (1998). [0081] 3. Johansson, I., Larsson, C., Ek, B. & Kjellbom, P. The major integral proteins of spinach leaf plasma membranes are putative aquaporins and are phosphorylated in response to Ca2+ and apoplastic water potential. Plant Cell 8, 1181-1191 (1996). [0082] 4. Tournaire-Roux, C., Sutka M., Javot H., Gout E., Gerbeau P., Luu D. T., Bligny R. & Maurel C. Cytosolic pH regulates root water transport during anoxic stress through gating of aquaporins. Nature 425, 393-397 (2003). [0083] 5. King, L. S., Kozono, D. & Agre, P. From structure to disease: the evolving tale of aquaporin biology. Nat Rev Mol Cell Biol 5, 687-698 (2004). [0084] 6. Agre, P. & Kozono, D. Aquaporin water channels: molecular mechanisms for human diseases. FEBS Lett 555, 72-78 (2003). [0085] 7. Johansson, I., Karlsson, M., Johanson, U., Larsson, C. & Kjellbom, P. The role of aquaporins in cellular and whole plant water balance. Biochim Biophys Acta 1465, 324-342 (2000). [0086] 8. Tamas, M. J., Karlgren S., Bill R. M., Hedfalk K., Allegri L., Ferreira M., Thevelein J. M., Rydstrom J., Mullins J. G. & Hohmann S. A short regulatory domain restricts glycerol transport through yeast Fps1p. J Biol Chem 278, 6337-6345 (2003). [0087] 9. Johanson, U., Karlsson M., Johansson I., Gustavsson S., Sjovall S., Fraysse L., Weig A. R. & Kjellbom P. The complete set of genes encoding major intrinsic proteins in Arabidopsis provides a framework for a new nomenclature for major intrinsic proteins in plants. Plant Physiol 126, 1358-1369 (2001). [0088] 10. Morishita, Y., Sakube, Y., Sasaki, S. & Ishibashi, K. Molecular mechanisms and drug development in aquaporin water channel diseases: aquaporin superfamily (superaquaporins): expansion of aquaporins restricted to multicellular organisms. J Pharmacol Sci 96, 276-279 (2004). [0089] 11. Borstlap, A. C. Early diversification of plant aquaporins. Trends Plant Sci 7, 529-530 (2002). [0090] 12. Murata, K., Mitsuoka K., Hirai T., Walz T., Agre P., Heymann J. B., Engel A. & Fujiyoshi Y. Structural determinants of water permeation through aquaporin-1. Nature 407, 599-605 (2000). [0091] 13. Sui, H., Han, B. G, Lee, J. K., Walian, P. & Jap, B. K. Structural basis of water-specific transport through the AQP1 water channel. Nature 414, 872-878 (2001). [0092] 14. Savage, D. F., Egea, P. F., Robles-Colmenares, Y., O'Connell, J. D. & Stroud, R. M. Architecture and selectivity in aquaporins: 2.5 a X-ray structure of aquaporin Z. PLoS Biol 1, E72 (2003). [0093] 15. Gonen, T., Sliz, P., Kistler, J., Cheng, Y. & Walz, T. Aquaporin-0 membrane junctions reveal the structure of a closed water pore. Nature 429, 193-197 (2004). [0094] 16. Harries, W. E., Akhavan, D., Miercke, L. J., Khademi, S. & Stroud, R. M. The channel architecture of aquaporin 0 at a 2.2-A resolution. Proc Natl Acad Sci USA 101, 14045-14050 (2004). [0095] 17. Fu, D. et al. Structure of a glycerol-conducting channel and the basis for its selectivity. Science 290, 481-486 (2000). [0096] 19. Jung, J. S., Preston, G M., Smith, B. L., Guggino, W. B. & Agre, P. Molecular structure of the water channel through aquaporin CHIP. The hourglass model. J Biol Chem 269, 14648-14654 (1994). [0097] 21. de Groot, B. L. & Grubmuller, H. Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF. Science 294, 2353-2357 (2001). [0098] 23. Smart, O, S., Goodfellow, J. M. & Wallace, B. A. The pore dimensions of gramicidin A. Biophys J 65, 2455-2460 (1993). [0099] 24. Zelenina, M., Bondar, A. A., Zelenin, S. & Aperia, A. Nickel and extracellular acidification inhibit the water permeability of human aquaporin-3 in lung epithelial cells. J Biol Chem 278, 30037-30043 (2003). [0100] 25. Zelenina, M., Tritto, S., Bondar, A. A., Zelenin, S. & Aperia, A. Copper inhibits the water and glycerol permeability of aquaporin-3. J Biol Chem 279, 51939-51943 (2004). [0101] 26. Madsen, D. & Kleywegt, G. J. Interactive motif and fold recognition in protein structures. J Appl Crystallogr 35, 137-139 (2001). [0102] 27. Saadoun, S., Papadopoulos, M. C., Hara-Chikuma, M. & Verkman, A. S. Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature 434, 786-792 (2005). [0103] 28. Karlsson, M., Fotiadis D., Sjovall S., Johansson I., Hedfalk K., Engel A. & Kjellbom P. Reconstitution of water channel function of an aquaporin overexpressed and purified from Pichia pastoris. FEBS Lett 537, 68-72 (2003). [0104] 29. Bailey, S. The CCP4 Suite: Programs for Protein Crystallography. Acta Crystallogr D 50, 760-763 (1994). [0105] 30. Jones, T. A., Zou, J.-Y., Cowan, S. W. & Kjeldgaard, M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Cryst A 47, 110-119 (1991). [0106] 31. Morris, R. J., Perrakis, A. & Lamzin, V. S. ARP/wARP and automatic interpretation of protein electron density maps. Methods Enzymol 374, 229-244 (2003). [0107] 32. Brunger, A. T., Adams P. D., Clore G. M., DeLano W. L., Gros R, Grosse-Kunstleve R. W., Jiang J. S., Kuszewski J., Nilges M., Pannu N. S., Read R. J., Rice L. M., Simonson T. & Warren G. L. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr D 54, 905-921 (1998). [0108] 33. Laskowski, R. A., Rullmannn, J. A., MacArthur, M. W., Kaptein, R. & Thornton, J. M. AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J Biomol NMR 8, 477-486 (1996). [0109] 34. Madsen, D. & Kleywegt, G. J. Interactive motif and fold recognition in protein structures. J Appl Crystallogr 35, 137-139 (2001). [0110] 35. Han B. G., Guliaev A. B., Walian P. J. & Jap B. K. Water transport in AQP0 aquaporin: molecular dynamics studies. J Mol Biol 360, 285-296 (2006). [0111] 36. Tornroth-Horsefield S., Wang Y., Hedfalk K., Johanson U., Karlsson M., Tajkhorshid E., Neutze R. & Kjellbom P. Structural mechanism of plant aquaporin gating. Nature 439, 688-694 (2006) [0112] 37. Kukulski W., Schenk A. D., Johanson U., Braun T., de Groot B. L., Fotiadis D., Kjellbom P. & Engel A. The 5 Å structure of heterologously expressed plant aquaporin SoPIP2;1. J Mol Biol 350, 611-616 (2005). [0113] 38. Yang B. & Verkman A. S. Water and glycerol permeability of aquaporins 1-5 and MIP determined quantitatively by expression of epitope-tagged constructs in Xenopus oocytes. J Biol Chem 272, 16140-16146 (1997). [0114] 39. Ma T., Yang B., Kuo W. L. & Verkman A S. cDNA cloning and gene structure of a novel water channel expressed exclusively in human kidney: evidence for a gene cluster of aquaporins at chromosome locus 12q13. Genomics 35, 543-550 (1996). [0115] 40. Kondo H., Shimomura I., Kishida K., Kuriyama H., Makino Y., Nishizawa H., Matsuda M., Maeda N., Nagaretani H., Kihara S., Kurachi Y., Nakamura T., Funahashi T. & Matsuzawa Y. Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation. Eur J Biochem 269, 1814-1826 (2002). [0116] 41. Ishibashi K., Kuwahara M., Kageyama Y., Tohsaka A., Marumo F. & Sasaki S. Cloning and functional expression of a second new aquaporin abundantly expressed in testis. Biochem Biophys Res Commun. 237, 714-718 (1997). [0117] 42. Kuriyama H., Kawamoto S., Ishida N., Ohno I., Mita S., Matsuzawa Y., Matsubara K. & Okubo K. Molecular cloning and expression of a novel human aquaporin from adipose tissue with glycerol permeability. Biochem Biophys Res Commun 241, 53-58 (1997). [0118] 43. Ishibashi K., Morinaga T., Kuwahara M., Sasaki S. & Imai M. Cloning and identification of a new member of water channel (AQP10) as an aquaglyceroporin. Biochim Biophys Acta 1576, 335-340 (2002). [0119] 44. Gorelick D. A., Praetorius J., Tsunenari T., Nielsen S. & Agre P. Aquaporin-11: a channel protein lacking apparent transport function expressed in brain. BMC Biochem 7, 14 (2006).
Sequence CWU
1
91129DNAArtificial SequenceForward PCR Primer EcoRI-YPM28A 1cggaattcaa
aatgtctaag gaagtaagt
29226DNAArtificial SequenceReverse PCR Primer PM28A-REV 2gaagatcttt
aattggtagg gttgct 263287PRTZea
mays 3Met Glu Gly Lys Glu Glu Asp Val Arg Leu Gly Ala Asn Lys Phe Ser1
5 10 15Glu Arg His Ala Ile
Gly Thr Ala Ala Gln Gly Thr Asp Asp Lys Asp 20
25 30Tyr Lys Glu Pro Pro Pro Ala Pro Leu Phe Glu Pro
Gly Glu Leu Lys 35 40 45Ser Trp
Ser Phe Tyr Arg Pro Gly Ile Ala Glu Phe Val Ala Thr Phe 50
55 60Leu Phe Leu Tyr Ile Ser Ile Leu Thr Val Met
Gly Val Ser Lys Ser65 70 75
80Thr Ser Lys Cys Ala Thr Val Gly Ile Gln Gly Ile Ala Trp Ser Phe
85 90 95Gly Gly Met Ile Leu
Ala Leu Val Tyr Cys Thr Ala Gly Ile Ser Gly 100
105 110His Ile Asn Pro Ala Val Thr Phe Gly Leu Phe Leu
Ala Arg Lys Leu 115 120 125Ser Leu
Thr Arg Ala Val Phe Tyr Ile Ile Met Gln Cys Leu Gly Ala 130
135 140Ile Cys Gly Arg Gly Val Val Lys Gly Phe Gln
Gln Gly Leu Tyr Met145 150 155
160Gly Asn Gly Gly Arg Arg Asn Val Val Ala Pro Gly Tyr Thr Lys Gly
165 170 175Asp Gly Leu Gly
Ala Glu Ile Val Gly Thr Phe Ile Leu Val Tyr Thr 180
185 190Val Phe Ser Ala Thr Asp Ala Lys Arg Arg Ala
Arg Asp Ser His Val 195 200 205Pro
Ile Leu Ala Pro Leu Pro Ile Gly Phe Ala Val Phe Leu Val His 210
215 220Leu Ala Thr Met Gly Ile Thr Gly Thr Gly
Ile Asn Pro Ala Arg Ser225 230 235
240Leu Gly Ala Ala Val Ile Tyr Asn Gln His His Ala Trp Ala Asp
His 245 250 255Trp Ile Phe
Trp Val Gly Pro Phe Ile Gly Ala Ala Leu Ala Ala Ile 260
265 270Tyr His Gln Val Ile Ile Arg Ala Ile Pro
Phe Lys Ser Arg Ser 275 280
2854289PRTZea mays 4Met Glu Gly Lys Glu Glu Asp Val Arg Leu Gly Ala Asn
Lys Phe Ser1 5 10 15Glu
Arg Gln Pro Ile Gly Thr Ala Ala Gln Gly Ala Ala Asp Asp Lys 20
25 30Asp Tyr Lys Glu Pro Pro Pro Ala
Pro Leu Phe Glu Pro Gly Glu Leu 35 40
45Lys Ser Trp Ser Phe Tyr Arg Ala Gly Ile Ala Glu Phe Val Ala Thr
50 55 60Phe Leu Phe Leu Tyr Ile Thr Ile
Leu Thr Val Met Gly Val Ser Lys65 70 75
80Ser Thr Ser Lys Cys Ala Thr Val Gly Ile Gln Gly Ile
Ala Trp Ser 85 90 95Phe
Gly Gly Met Ile Phe Ala Leu Val Tyr Cys Thr Ala Gly Ile Ser
100 105 110Gly Gly His Ile Asn Pro Ala
Val Thr Phe Gly Leu Phe Leu Ala Arg 115 120
125Lys Leu Ser Leu Thr Arg Ala Leu Phe Tyr Ile Ile Met Gln Cys
Leu 130 135 140Gly Ala Val Cys Gly Ala
Gly Val Val Lys Gly Phe Gln Gln Gly Leu145 150
155 160Tyr Met Gly Asn Gly Gly Gly Ala Asn Val Val
Ala Pro Gly Tyr Thr 165 170
175Lys Gly Asp Gly Leu Gly Ala Glu Ile Val Gly Thr Phe Ile Leu Val
180 185 190Tyr Thr Val Phe Ser Ala
Thr Asp Ala Lys Arg Asn Ala Arg Asp Ser 195 200
205His Val Pro Ile Leu Ala Pro Leu Pro Ile Gly Phe Ala Val
Phe Leu 210 215 220Val His Leu Ala Thr
Ile Pro Ile Thr Gly Thr Gly Ile Asn Pro Ala225 230
235 240Arg Ser Leu Gly Ala Ala Ile Ile Tyr Asn
Arg Asp His Ala Trp Asn 245 250
255Asp His Trp Ile Phe Trp Val Gly Pro Phe Ile Gly Ala Ala Leu Ala
260 265 270Ala Ile Tyr His Gln
Val Ile Ile Arg Ala Ile Pro Phe Lys Ser Arg 275
280 285Ser 5292PRTZea mays 5Met Glu Gly Lys Glu Glu Asp
Val Arg Leu Gly Ala Asn Lys Phe Ser1 5 10
15Glu Arg Gln Pro Ile Gly Thr Ala Ala Gln Gly Ala Gly
Ala Gly Asp 20 25 30Asp Asp
Lys Asp Tyr Lys Glu Pro Pro Pro Ala Pro Leu Phe Glu Pro 35
40 45Gly Glu Leu Lys Ser Trp Ser Phe Tyr Arg
Ala Gly Ile Ala Glu Phe 50 55 60Val
Ala Thr Phe Leu Phe Leu Tyr Ile Thr Val Leu Thr Val Met Gly65
70 75 80Val Ser Lys Ser Thr Ser
Lys Cys Ala Thr Val Gly Ile Gln Gly Ile 85
90 95Ala Trp Ser Phe Gly Gly Met Ile Phe Ala Leu Val
Tyr Cys Thr Ala 100 105 110Gly
Ile Ser Gly Gly His Ile Asn Pro Ala Val Thr Phe Gly Leu Phe 115
120 125Leu Ala Arg Lys Leu Ser Leu Thr Arg
Ala Ile Phe Tyr Ile Ile Met 130 135
140Gln Cys Leu Gly Ala Ile Cys Gly Ala Gly Val Val Lys Gly Phe Gln145
150 155 160Gln Gly Leu Tyr
Met Gly Asn Gly Gly Gly Ala Asn Val Val Ala Pro 165
170 175Gly Tyr Thr Lys Gly Asp Gly Leu Gly Ala
Glu Ile Val Gly Thr Phe 180 185
190Ile Leu Val Tyr Thr Val Phe Ser Ala Thr Asp Ala Lys Arg Asn Ala
195 200 205Arg Asp Ser His Val Pro Ile
Leu Ala Pro Leu Pro Ile Gly Phe Ala 210 215
220Val Phe Leu Val His Leu Ala Thr Ile Pro Ile Thr Gly Thr Gly
Ile225 230 235 240Asn Pro
Ala Arg Ser Leu Gly Ala Ala Ile Ile Tyr Asn Arg Asp His
245 250 255Ala Trp Ser Asp His Trp Ile
Phe Trp Val Gly Pro Phe Ile Gly Ala 260 265
270Ala Leu Ala Ala Ile Tyr His Gln Val Ile Ile Arg Ala Ile
Pro Phe 275 280 285Lys Ser Arg Ser
2906292PRTZea mays 6Met Glu Gly Lys Glu Glu Asp Val Arg Leu Gly Ala
Asn Lys Phe Ser1 5 10
15Glu Arg Gln Pro Ile Gly Thr Ala Ala Gln Gly Ala Gly Ala Gly Asp
20 25 30Asp Asp Lys Asp Tyr Lys Glu
Pro Pro Pro Ala Pro Leu Phe Glu Pro 35 40
45Gly Glu Leu Lys Ser Trp Ser Phe Tyr Arg Ala Gly Ile Ala Glu
Phe 50 55 60Val Ala Thr Phe Leu Phe
Leu Tyr Ile Thr Val Leu Thr Val Met Gly65 70
75 80Val Ser Lys Ser Thr Ser Lys Cys Ala Thr Val
Gly Ile Gln Gly Ile 85 90
95Ala Trp Ser Phe Gly Gly Met Ile Phe Ala Leu Val Tyr Cys Thr Ala
100 105 110Gly Ile Ser Gly Gly His
Ile Asn Pro Ala Val Thr Phe Gly Leu Phe 115 120
125Leu Ala Arg Lys Leu Ser Leu Thr Arg Ala Ile Phe Tyr Ile
Ile Met 130 135 140Gln Cys Leu Gly Ala
Ile Cys Gly Ala Gly Val Val Lys Gly Phe Gln145 150
155 160Gln Gly Leu Tyr Met Gly Asn Gly Gly Gly
Ala Asn Val Val Ala Pro 165 170
175Gly Tyr Thr Lys Gly Asp Gly Leu Gly Ala Glu Ile Val Gly Thr Phe
180 185 190Ile Leu Val Tyr Thr
Val Phe Ser Ala Thr Asp Ala Lys Arg Asn Ala 195
200 205Arg Asp Ser His Val Pro Ile Leu Ala Pro Leu Pro
Ile Gly Phe Ala 210 215 220Val Phe Leu
Val His Leu Ala Thr Ile Pro Ile Thr Gly Thr Gly Ile225
230 235 240Asn Pro Ala Arg Ser Leu Gly
Ala Ala Ile Ile Tyr Asn Arg Asp His 245
250 255Ala Trp Ser Asp His Trp Ile Phe Trp Val Gly Pro
Phe Ile Gly Ala 260 265 270Ala
Leu Ala Ala Ile Tyr His Gln Val Ile Ile Arg Ala Ile Pro Phe 275
280 285Lys Ser Arg Ser 2907288PRTZea mays
7Met Glu Gly Lys Glu Glu Asp Val Arg Leu Gly Ala Asn Arg Tyr Ser1
5 10 15Glu Arg Gln Pro Ile Gly
Thr Ala Ala Gln Gly Thr Glu Glu Lys Asp 20 25
30Tyr Lys Glu Pro Pro Pro Ala Pro Leu Phe Glu Ala Glu
Glu Leu Thr 35 40 45Ser Trp Ser
Phe Tyr Arg Ala Gly Ile Ala Glu Phe Val Ala Thr Phe 50
55 60Leu Phe Leu Tyr Ile Ser Ile Leu Thr Val Met Gly
Val Ser Lys Ser65 70 75
80Ser Ser Lys Cys Ala Thr Val Gly Ile Gln Gly Ile Ala Trp Ser Phe
85 90 95Gly Gly Met Ile Phe Ala
Leu Val Tyr Cys Thr Ala Gly Ile Ser Gly 100
105 110Gly His Ile Asn Pro Ala Val Thr Phe Gly Leu Phe
Leu Ala Arg Lys 115 120 125Leu Ser
Leu Thr Arg Ala Leu Phe Tyr Met Val Met Gln Cys Leu Gly 130
135 140Ala Ile Cys Gly Ala Gly Val Val Lys Gly Phe
Gln Glu Gly Leu Tyr145 150 155
160Met Gly Ala Gly Gly Gly Ala Asn Ala Val Asn Pro Gly Tyr Thr Lys
165 170 175Gly Asp Gly Leu
Gly Ala Glu Ile Val Gly Thr Phe Val Leu Val Tyr 180
185 190Thr Val Phe Ser Ala Thr Asp Ala Lys Arg Ser
Ala Arg Asp Ser His 195 200 205Val
Pro Ile Leu Ala Pro Leu Pro Ile Gly Phe Ala Val Phe Leu Val 210
215 220His Leu Ala Thr Ile Pro Ile Thr Gly Thr
Gly Ile Asn Pro Ala Arg225 230 235
240Ser Leu Gly Ala Ala Ile Val Tyr Asn Arg Ser His Ala Trp Asn
Asp 245 250 255His Trp Ile
Phe Trp Val Gly Pro Phe Ile Gly Ala Ala Leu Ala Ala 260
265 270Ile Tyr His Val Val Ile Ile Arg Ala Leu
Pro Phe Lys Ser Arg Asp 275 280
2858296PRTZea mays 8Met Ala Gly Gly Thr Leu Gln Asp Arg Ser Glu Glu Glu
Asp Val Arg1 5 10 15Val
Gly Val Asp Arg Phe Pro Glu Arg Gln Pro Ile Gly Thr Ala Ala 20
25 30Asp Asp Leu Gly Arg Asp Tyr Ser
Glu Pro Pro Ala Ala Pro Leu Phe 35 40
45Glu Ala Ser Glu Leu Ser Ser Trp Ser Phe Tyr Arg Ala Gly Ile Ala
50 55 60Glu Phe Val Ala Thr Phe Leu Phe
Leu Tyr Val Thr Val Leu Thr Val65 70 75
80Met Gly Val Ser Lys Ser Pro Ser Lys Cys Gly Thr Val
Gly Ile Gln 85 90 95Gly
Ile Ala Trp Ala Phe Gly Gly Met Ile Phe Ala Leu Val Tyr Cys
100 105 110Thr Ala Gly Val Ser Gly Gly
His Ile Asn Pro Ala Val Thr Phe Gly 115 120
125Leu Leu Leu Ala Arg Lys Leu Ser Leu Thr Arg Ala Val Tyr Tyr
Val 130 135 140Val Met Gln Cys Leu Gly
Ala Val Cys Gly Ala Gly Val Val Lys Ala145 150
155 160Phe Gly Ser Ala Leu Tyr Glu Ser Ala Gly Gly
Gly Ala Asn Ala Val 165 170
175Ser Pro Gly Tyr Thr Lys Gly Asp Gly Leu Gly Ala Glu Val Val Gly
180 185 190Thr Phe Val Leu Val Tyr
Thr Val Phe Ser Ala Thr Asp Ala Lys Arg 195 200
205Thr Ala Arg Asp Ser His Val Pro Ala Leu Ala Pro Leu Pro
Ile Gly 210 215 220Phe Ala Val Phe Leu
Val His Leu Ala Thr Ile Pro Ile Thr Gly Thr225 230
235 240Gly Ile Asn Pro Ala Arg Ser Leu Gly Ala
Ala Ile Ile Tyr Asp Asn 245 250
255Pro His Gly Trp His Gly His Trp Ile Phe Trp Val Gly Pro Phe Ala
260 265 270Gly Ala Ala Leu Ala
Ala Val Tyr His Gln Val Val Leu Arg Ala Ile 275
280 285Pro Phe Lys Ser Ser Ala His Tyr 290
2959286PRTArabidopsis thaliana 9Met Glu Gly Lys Glu Glu Asp Val Arg
Val Gly Ala Asn Lys Phe Pro1 5 10
15Glu Arg Gln Pro Ile Gly Thr Ser Ala Gln Ser Asp Lys Asp Tyr
Lys 20 25 30Glu Pro Pro Pro
Ala Pro Phe Phe Glu Pro Gly Glu Leu Ser Ser Trp 35
40 45Ser Phe Trp Arg Ala Gly Ile Ala Glu Phe Ile Ala
Thr Phe Leu Phe 50 55 60Leu Tyr Ile
Thr Val Leu Thr Val Met Gly Val Lys Arg Ser Pro Asn65 70
75 80Met Cys Ala Ser Val Gly Ile Gln
Gly Ile Ala Trp Ala Phe Gly Gly 85 90
95Met Ile Phe Ala Leu Val Tyr Cys Thr Ala Gly Ile Ser Gly
Gly His 100 105 110Ile Asn Pro
Ala Val Thr Phe Gly Leu Phe Leu Ala Arg Lys Leu Ser 115
120 125Leu Thr Arg Ala Leu Tyr Tyr Ile Val Met Gln
Cys Leu Gly Ala Ile 130 135 140Cys Gly
Ala Gly Val Val Lys Gly Phe Gln Pro Lys Gln Tyr Gln Ala145
150 155 160Leu Gly Gly Gly Ala Asn Thr
Val Ala His Gly Tyr Thr Lys Gly Ser 165
170 175Gly Leu Gly Ala Glu Ile Ile Gly Thr Phe Val Leu
Val Tyr Thr Val 180 185 190Phe
Ser Ala Thr Asp Ala Lys Arg Asn Ala Arg Asp Ser His Val Pro 195
200 205Ile Leu Ala Pro Leu Pro Ile Gly Phe
Ala Val Phe Leu Val His Leu 210 215
220Ala Thr Ile Pro Ile Thr Gly Thr Gly Ile Asn Pro Ala Arg Ser Leu225
230 235 240Gly Ala Ala Ile
Ile Tyr Asn Lys Asp His Ser Trp Asp Asp His Trp 245
250 255Val Phe Trp Val Gly Pro Phe Ile Gly Ala
Ala Leu Ala Ala Leu Tyr 260 265
270His Val Val Val Ile Arg Ala Ile Pro Phe Lys Ser Arg Ser 275
280 28510286PRTArabidopsis thaliana 10Met
Glu Gly Lys Glu Glu Asp Val Arg Val Gly Ala Asn Lys Phe Pro1
5 10 15Glu Arg Gln Pro Ile Gly Thr
Ser Ala Gln Ser Asp Lys Asp Tyr Lys 20 25
30Glu Pro Pro Pro Ala Pro Leu Phe Glu Pro Gly Glu Leu Ala
Ser Trp 35 40 45Ser Phe Trp Arg
Ala Gly Ile Ala Glu Phe Ile Ala Thr Phe Leu Phe 50 55
60Leu Tyr Ile Thr Val Leu Thr Val Met Gly Val Lys Arg
Ser Pro Asn65 70 75
80Met Cys Ala Ser Val Gly Ile Gln Gly Ile Ala Trp Ala Phe Gly Gly
85 90 95Met Ile Phe Ala Leu Val
Tyr Cys Thr Ala Gly Ile Ser Gly Gly His 100
105 110Ile Asn Pro Ala Val Thr Phe Gly Leu Phe Leu Ala
Arg Lys Leu Ser 115 120 125Leu Thr
Arg Ala Val Tyr Tyr Ile Val Met Gln Cys Leu Gly Ala Ile 130
135 140Cys Gly Ala Gly Val Val Lys Gly Phe Gln Pro
Lys Gln Tyr Gln Ala145 150 155
160Leu Gly Gly Gly Ala Asn Thr Ile Ala His Gly Tyr Thr Lys Gly Ser
165 170 175Gly Leu Gly Ala
Glu Ile Ile Gly Thr Phe Val Leu Val Tyr Thr Val 180
185 190Phe Ser Ala Thr Asp Ala Lys Arg Asn Ala Arg
Asp Ser His Val Pro 195 200 205Ile
Leu Ala Pro Leu Pro Ile Gly Phe Ala Val Phe Leu Val His Leu 210
215 220Ala Thr Ile Pro Ile Thr Gly Thr Gly Ile
Asn Pro Ala Arg Ser Leu225 230 235
240Gly Ala Ala Ile Ile Phe Asn Lys Asp Asn Ala Trp Asp Asp His
Trp 245 250 255Val Phe Trp
Val Gly Pro Phe Ile Gly Ala Ala Leu Ala Ala Leu Tyr 260
265 270His Val Ile Val Ile Arg Ala Ile Pro Phe
Lys Ser Arg Ser 275 280
28511286PRTArabidopsis thaliana 11Met Glu Gly Lys Glu Glu Asp Val Arg Val
Gly Ala Asn Lys Phe Pro1 5 10
15Glu Arg Gln Pro Ile Gly Thr Ser Ala Gln Thr Asp Lys Asp Tyr Lys
20 25 30Glu Pro Pro Pro Ala Pro
Phe Phe Glu Pro Gly Glu Leu Ser Ser Trp 35 40
45Ser Phe Tyr Arg Ala Gly Ile Ala Glu Phe Ile Ala Thr Phe
Leu Phe 50 55 60Leu Tyr Ile Thr Val
Leu Thr Val Met Gly Val Lys Arg Ala Pro Asn65 70
75 80Met Cys Ala Ser Val Gly Ile Gln Gly Ile
Ala Trp Ala Phe Gly Gly 85 90
95Met Ile Phe Ala Leu Val Tyr Cys Thr Ala Gly Ile Ser Gly Gly His
100 105 110Ile Asn Pro Ala Val
Thr Phe Gly Leu Phe Leu Ala Arg Lys Leu Ser 115
120 125Leu Thr Arg Ala Val Phe Tyr Ile Val Met Gln Cys
Leu Gly Ala Ile 130 135 140Cys Gly Ala
Gly Val Val Lys Gly Phe Gln Pro Asn Pro Tyr Gln Thr145
150 155 160Leu Gly Gly Gly Ala Asn Thr
Val Ala His Gly Tyr Thr Lys Gly Ser 165
170 175Gly Leu Gly Ala Glu Ile Ile Gly Thr Phe Val Leu
Val Tyr Thr Val 180 185 190Phe
Ser Ala Thr Asp Ala Lys Arg Ser Ala Arg Asp Ser His Val Pro 195
200 205Ile Leu Ala Pro Leu Pro Ile Gly Phe
Ala Val Phe Leu Val His Leu 210 215
220Ala Thr Ile Pro Ile Thr Gly Thr Gly Ile Asn Pro Ala Arg Ser Leu225
230 235 240Gly Ala Ala Ile
Ile Tyr Asn Lys Asp His Ala Trp Asp Asp His Trp 245
250 255Ile Phe Trp Val Gly Pro Phe Ile Gly Ala
Ala Leu Ala Ala Leu Tyr 260 265
270His Gln Leu Val Ile Arg Ala Ile Pro Phe Lys Ser Arg Ser 275
280 28512287PRTArabidopsis thaliana 12Met
Glu Gly Lys Glu Glu Asp Val Arg Val Gly Ala Asn Lys Phe Pro1
5 10 15Glu Arg Gln Pro Ile Gly Thr
Ser Ala Gln Ser Thr Asp Lys Asp Tyr 20 25
30Lys Glu Pro Pro Pro Ala Pro Leu Phe Glu Pro Gly Glu Leu
Ser Ser 35 40 45Trp Ser Phe Tyr
Arg Ala Gly Ile Ala Glu Phe Ile Ala Thr Phe Leu 50 55
60Phe Leu Tyr Ile Thr Val Leu Thr Val Met Gly Val Lys
Arg Ala Pro65 70 75
80Asn Met Cys Ala Ser Val Gly Ile Gln Gly Ile Ala Trp Ala Phe Gly
85 90 95Gly Met Ile Phe Ala Leu
Val Tyr Cys Thr Ala Gly Ile Ser Gly Gly 100
105 110His Ile Asn Pro Ala Val Thr Phe Gly Leu Phe Leu
Ala Arg Lys Leu 115 120 125Ser Leu
Thr Arg Ala Val Phe Tyr Met Ile Met Gln Cys Leu Gly Ala 130
135 140Ile Cys Gly Ala Gly Val Val Lys Gly Phe Gln
Pro Thr Pro Tyr Gln145 150 155
160Thr Leu Gly Gly Gly Ala Asn Thr Val Ala His Gly Tyr Thr Lys Gly
165 170 175Ser Gly Leu Gly
Ala Glu Ile Ile Gly Thr Phe Val Leu Val Tyr Thr 180
185 190Val Phe Ser Ala Thr Asp Ala Lys Arg Ser Ala
Arg Asp Ser His Val 195 200 205Pro
Ile Leu Ala Pro Leu Pro Ile Gly Phe Ala Val Phe Leu Val His 210
215 220Leu Ala Thr Ile Pro Ile Thr Gly Thr Gly
Ile Asn Pro Ala Arg Ser225 230 235
240Leu Gly Ala Ala Ile Ile Tyr Asn Lys Asp His Ser Trp Asp Asp
His 245 250 255Trp Ile Phe
Trp Val Gly Pro Phe Ile Gly Ala Ala Leu Ala Ala Leu 260
265 270Tyr His Gln Ile Val Ile Arg Ala Ile Pro
Phe Lys Ser Lys Ser 275 280
28513287PRTArabidopsis thaliana 13Met Glu Gly Lys Glu Glu Asp Val Asn Val
Gly Ala Asn Lys Phe Pro1 5 10
15Glu Arg Gln Pro Ile Gly Thr Ala Ala Gln Thr Glu Ser Lys Asp Tyr
20 25 30Lys Glu Pro Pro Pro Ala
Pro Phe Phe Glu Pro Gly Glu Leu Lys Ser 35 40
45Trp Ser Phe Tyr Arg Ala Gly Ile Ala Glu Phe Ile Ala Thr
Phe Leu 50 55 60Phe Leu Tyr Val Thr
Val Leu Thr Val Met Gly Val Lys Arg Ala Pro65 70
75 80Asn Met Cys Ala Ser Val Gly Ile Gln Gly
Ile Ala Trp Ala Phe Gly 85 90
95Gly Met Ile Phe Ala Leu Val Tyr Cys Thr Ala Gly Ile Ser Gly Gly
100 105 110His Ile Asn Pro Ala
Val Thr Phe Gly Leu Phe Leu Ala Arg Lys Leu 115
120 125Ser Leu Thr Arg Ala Leu Phe Tyr Ile Val Met Gln
Cys Leu Gly Ala 130 135 140Ile Cys Gly
Ala Gly Val Val Lys Gly Phe Gln Pro Gly Leu Tyr Gln145
150 155 160Thr Asn Gly Gly Gly Ala Asn
Val Val Ala His Gly Tyr Thr Lys Gly 165
170 175Ser Gly Leu Gly Ala Glu Ile Val Gly Thr Phe Val
Leu Val Tyr Thr 180 185 190Val
Phe Ser Ala Thr Asp Ala Lys Arg Ser Ala Arg Asp Ser His Val 195
200 205Pro Ile Leu Ala Pro Leu Pro Ile Gly
Phe Ala Val Phe Leu Val His 210 215
220Leu Ala Thr Ile Pro Ile Thr Gly Thr Gly Ile Asn Pro Ala Arg Ser225
230 235 240Leu Gly Ala Ala
Ile Ile Tyr Asn Lys Asp His Ala Trp Asp Asp His 245
250 255Trp Ile Phe Trp Val Gly Pro Phe Ile Gly
Ala Ala Leu Ala Ala Leu 260 265
270Tyr His Gln Ile Val Ile Arg Ala Ile Pro Phe Lys Ser Lys Thr
275 280 28514288PRTPicea abies 14Met Glu
Gly Lys Glu Glu Asp Val Arg Leu Gly Ala Asn Lys Tyr Ser1 5
10 15Glu Arg Gln Pro Leu Gly Thr Ala
Ala Gln Thr Arg Glu Lys Asp Tyr 20 25
30Lys Asp Ser Gly Pro Ala Pro Leu Phe Glu Pro Gly Glu Leu Ala
Ser 35 40 45Trp Ser Phe Trp Arg
Ala Gly Ile Ala Glu Phe Met Ala Thr Phe Leu 50 55
60Phe Leu Tyr Ile Thr Ile Leu Thr Val Met Gly Val Lys Arg
Ser Asp65 70 75 80Asp
Val Cys Thr Gly Ser Val Gly Ile Gln Gly Ile Ala Trp Ala Phe
85 90 95Gly Gly Met Ile Phe Cys Leu
Val Tyr Cys Thr Ala Gly Ile Ser Gly 100 105
110Gly His Ile Asn Pro Ala Val Thr Phe Gly Leu Phe Leu Ala
Arg Lys 115 120 125Leu Ser Leu Pro
Arg Ala Val Phe Tyr Met Ile Cys Gln Cys Leu Gly 130
135 140Ala Ile Cys Gly Ala Gly Val Val Lys Gly Phe Met
Glu Ser Glu Tyr145 150 155
160Glu Met Asp Gly Gly Gly Ala Asn Ser Val Ala His Gly Tyr Thr Lys
165 170 175Gly Asp Gly Leu Gly
Ala Glu Ile Val Gly Thr Phe Val Leu Val Tyr 180
185 190Thr Val Phe Ser Ala Thr Asp Ala Lys Arg Ser Ala
Arg Asp Ser His 195 200 205Val Pro
Met Leu Ala Pro Leu Pro Ile Gly Phe Ala Val Phe Leu Val 210
215 220His Leu Ala Thr Ile Pro Ile Thr Gly Thr Gly
Ile Asn Pro Ala Arg225 230 235
240Ser Leu Gly Ala Ala Ile Ile Tyr Asn Lys Ser His Ala Trp Asp Asp
245 250 255His Trp Ile Phe
Trp Val Gly Pro Phe Leu Gly Ala Gly Leu Ala Ala 260
265 270Phe Tyr His Gln Met Ile Ile Arg Ala Ile Pro
Phe Lys Thr Arg Ser 275 280
28515286PRTPhyscomitrella patens 15Met Ala Asp Arg Gly Asp Asp Val Ala
Val Gly Ala Ser Arg His Glu1 5 10
15Arg Asn Pro Leu Gly Thr Ser Ala Gln Thr Arg Glu Lys Asp Tyr
Ile 20 25 30Glu Pro Ala Ser
Ser Pro Phe Ile Asp Pro Val Glu Leu Gly Arg Trp 35
40 45Ser Phe Trp Arg Ala Gly Ile Ala Glu Phe Phe Ala
Ser Phe Leu Phe 50 55 60Leu Tyr Ile
Thr Val Gln Thr Val Met Gly His Asn Arg Gly Asp Ala65 70
75 80Cys Ala Gly Val Gly Ile Gln Gly
Ile Ala Trp Ala Phe Gly Gly Met 85 90
95Ile Phe Thr Leu Val Tyr Cys Thr Ala Gly Ile Ser Gly Gly
His Ile 100 105 110Asn Pro Ala
Val Thr Phe Gly Leu Phe Leu Ala Arg Lys Val Thr Phe 115
120 125Pro Arg Thr Val Leu Tyr Ile Val Cys Gln Cys
Leu Gly Ala Ile Cys 130 135 140Gly Ala
Gly Ala Val Lys Gly Phe Gln Pro Asp Phe Tyr Gln Ser Val145
150 155 160Gly Gly Gly Ala Asn Thr Val
Ala His Gly Tyr Thr Lys Gly Asp Gly 165
170 175Leu Gly Ala Glu Ile Val Gly Thr Phe Val Leu Val
Tyr Thr Val Phe 180 185 190Ser
Ala Thr Asp Ala Lys Arg Asn Ala Arg Asp Ser His Val Pro Leu 195
200 205Leu Ala Pro Leu Pro Ile Gly Phe Ala
Val Phe Leu Val His Leu Ala 210 215
220Thr Ile Pro Ile Thr Gly Thr Ser Ile Asn Pro Ala Arg Ser Leu Gly225
230 235 240Ala Ala Val Ile
Trp Asn Arg Asp Gln Ala Trp Asn Asp His Trp Ile 245
250 255Phe Trp Val Gly Pro Ile Leu Gly Ala Thr
Leu Ala Ala Met Tyr His 260 265
270Thr Leu Val Ile Arg Ala Ile Pro Phe Ser Ala Asn Arg Ala 275
280 28516290PRTZea mays 16Met Gly Lys Asp
Asp Val Ile Glu Ser Gly Ala Gly Gly Gly Glu Phe1 5
10 15Ala Ala Lys Asp Tyr Thr Asp Pro Pro Pro
Ala Pro Leu Ile Asp Ala 20 25
30Ala Glu Leu Gly Ser Trp Ser Leu Tyr Arg Ala Val Ile Ala Glu Phe
35 40 45Ile Ala Thr Leu Leu Phe Leu Tyr
Ile Thr Val Ala Thr Val Ile Gly 50 55
60Tyr Lys His Gln Thr Asp Ala Ser Ala Ser Gly Ala Asp Ala Ala Cys65
70 75 80Gly Gly Val Gly Val
Leu Gly Ile Ala Trp Ala Phe Gly Gly Met Ile 85
90 95Phe Val Leu Val Tyr Cys Thr Ala Gly Ile Ser
Gly Gly His Ile Asn 100 105
110Pro Ala Val Thr Phe Gly Leu Phe Leu Ala Arg Lys Val Ser Leu Val
115 120 125Arg Ala Leu Leu Tyr Ile Val
Ala Gln Cys Leu Gly Ala Ile Cys Gly 130 135
140Val Gly Leu Val Lys Ala Phe Gln Ser Ala Tyr Phe Asp Arg Tyr
Gly145 150 155 160Gly Gly
Ala Asn Ser Leu Ala Ser Gly Tyr Ser Arg Gly Thr Gly Leu
165 170 175Gly Ala Glu Ile Ile Gly Thr
Phe Val Leu Val Tyr Thr Val Phe Ser 180 185
190Ala Thr Asp Pro Lys Arg Asn Ala Arg Asp Ser His Val Pro
Val Leu 195 200 205Ala Pro Leu Pro
Ile Gly Phe Ala Val Phe Met Val His Leu Ala Thr 210
215 220Ile Pro Val Thr Gly Thr Gly Ile Asn Pro Ala Arg
Ser Leu Gly Ala225 230 235
240Ala Val Ile Tyr Asn Lys Asp Lys Pro Trp Asp Asp His Trp Ile Phe
245 250 255Trp Val Gly Pro Leu
Val Gly Ala Ala Ile Ala Ala Phe Tyr His Gln 260
265 270Tyr Ile Leu Arg Ala Gly Ala Ile Lys Ala Leu Gly
Ser Phe Arg Ser 275 280 285Asn Ala
29017292PRTZea mays 17Met Gly Lys Asp Asp Val Val Gln Ser Gly Ala Gly
Gly Gly Glu Phe1 5 10
15Ala Ala Lys Asp Tyr Thr Asp Pro Pro Pro Ala Pro Leu Val Asp Ala
20 25 30Ala Glu Leu Gly Ser Trp Ser
Leu Tyr Arg Ala Val Ile Ala Glu Phe 35 40
45Ile Ala Thr Leu Leu Phe Leu Tyr Val Thr Val Ala Thr Val Ile
Gly 50 55 60Tyr Lys His Gln Thr Asp
Ala Ser Ala Ser Gly Ala Gly Ala Asp Ala65 70
75 80Ala Cys Gly Gly Val Gly Val Leu Gly Ile Ala
Trp Ala Phe Gly Gly 85 90
95Met Ile Phe Val Leu Val Tyr Cys Thr Ala Gly Ile Ser Gly Gly His
100 105 110Ile Asn Pro Ala Val Thr
Phe Gly Leu Phe Leu Ala Arg Lys Val Ser 115 120
125Leu Val Arg Ala Leu Leu Tyr Met Val Ala Gln Cys Leu Gly
Ala Val 130 135 140Cys Gly Val Gly Leu
Val Lys Ala Phe Gln Ser Ala Tyr Phe Asp Arg145 150
155 160Tyr Gly Gly Gly Ala Asn Ser Leu Ala Ser
Gly Tyr Ser Arg Gly Ala 165 170
175Gly Leu Gly Ala Glu Ile Val Gly Thr Phe Val Leu Val Tyr Thr Val
180 185 190Phe Ser Ala Thr Asp
Pro Lys Arg Asn Ala Arg Asp Ser His Val Pro 195
200 205Val Leu Ala Pro Leu Pro Ile Gly Phe Ala Val Phe
Met Val His Leu 210 215 220Ala Thr Ile
Pro Val Thr Gly Thr Gly Ile Asn Pro Ala Arg Ser Leu225
230 235 240Gly Ala Ala Val Val Tyr Asn
Lys Asp Lys Pro Trp Asp Asp His Trp 245
250 255Ile Phe Trp Val Gly Pro Leu Leu Gly Ala Ala Ile
Ala Ala Phe Tyr 260 265 270His
Gln Tyr Ile Leu Arg Ala Gly Ala Ile Lys Ala Leu Gly Ser Phe 275
280 285Arg Ser Asn Ala 29018289PRTZea
mays 18Met Ala Lys Gln Asp Ile Glu Ala Ser Gly Pro Glu Ala Gly Glu Phe1
5 10 15Ser Ala Lys Asp Tyr
Thr Asp Pro Pro Pro Ala Pro Leu Ile Asp Ala 20
25 30Asp Glu Leu Thr Lys Trp Ser Leu Tyr Arg Ala Val
Ile Ala Glu Phe 35 40 45Ile Ala
Thr Leu Leu Phe Leu Tyr Ile Thr Val Ala Thr Val Ile Gly 50
55 60Tyr Lys His Gln Thr Asp Ala Ala Ala Ser Gly
Pro Asp Ala Ala Cys65 70 75
80Gly Gly Val Gly Ile Leu Gly Ile Ala Trp Ala Phe Gly Gly Met Ile
85 90 95Phe Ile Leu Val Tyr
Cys Thr Ala Gly Ile Ser Gly Gly His Ile Asn 100
105 110Pro Ala Val Thr Phe Gly Leu Phe Leu Ala Arg Lys
Val Ser Leu Val 115 120 125Arg Ala
Leu Leu Tyr Ile Ile Ala Gln Cys Leu Gly Ala Ile Cys Gly 130
135 140Val Gly Leu Val Lys Gly Phe Gln Ser Ala Tyr
Tyr Val Arg Tyr Gly145 150 155
160Gly Gly Ala Asn Glu Leu Ser Asp Gly Tyr Ser Lys Gly Thr Gly Leu
165 170 175Ala Ala Glu Ile
Ile Gly Thr Phe Val Leu Val Tyr Thr Val Phe Ser 180
185 190Ala Thr Asp Pro Lys Arg Ser Ala Arg Asp Ser
His Val Pro Val Leu 195 200 205Ala
Pro Leu Pro Ile Gly Phe Ala Val Phe Met Val His Leu Ala Thr 210
215 220Ile Pro Ile Thr Gly Thr Gly Ile Asn Pro
Ala Arg Ser Leu Gly Ala225 230 235
240Ala Val Ile Tyr Asn Lys Asp Lys Ala Trp Asp Asp Gln Trp Ile
Phe 245 250 255Trp Val Gly
Pro Leu Ile Gly Ala Ala Ile Ala Ala Ala Tyr His Gln 260
265 270Tyr Val Leu Arg Ala Ser Ala Thr Lys Leu
Gly Ser Tyr Arg Ser Asn 275 280
285Ala 19288PRTZea mays 19Met Ala Lys Asp Ile Glu Ala Ser Gly Pro Glu Ala
Gly Glu Phe Ser1 5 10
15Ala Lys Asp Tyr Thr Asp Pro Pro Pro Ala Pro Leu Ile Asp Ala Glu
20 25 30Glu Leu Thr Gln Trp Ser Leu
Tyr Arg Ala Val Ile Ala Glu Phe Ile 35 40
45Ala Thr Leu Leu Phe Leu Tyr Ile Thr Val Ala Thr Val Ile Gly
Tyr 50 55 60Lys His Gln Thr Asp Ala
Ser Ala Ser Gly Pro Asp Ala Ala Cys Gly65 70
75 80Gly Val Gly Ile Leu Gly Ile Ala Trp Ala Phe
Gly Gly Met Ile Phe 85 90
95Ile Leu Val Tyr Cys Thr Ala Gly Ile Ser Gly Gly His Ile Asn Pro
100 105 110Ala Val Thr Phe Gly Leu
Phe Leu Ala Arg Lys Val Ser Leu Val Arg 115 120
125Ala Leu Leu Tyr Ile Ile Ala Gln Cys Leu Gly Ala Ile Cys
Gly Val 130 135 140Gly Leu Val Lys Gly
Phe Gln Ser Ala Tyr Tyr Val Arg Tyr Gly Gly145 150
155 160Gly Ala Asn Glu Leu Ser Asp Gly Tyr Ser
Lys Gly Thr Gly Leu Ala 165 170
175Ala Glu Ile Ile Gly Thr Phe Val Leu Val Tyr Thr Val Phe Ser Ala
180 185 190Thr Asp Pro Lys Arg
Ser Ala Arg Asp Ser His Val Pro Val Leu Ala 195
200 205Pro Leu Pro Ile Gly Phe Ala Val Phe Met Val His
Leu Ala Thr Ile 210 215 220Pro Ile Thr
Gly Thr Gly Ile Asn Pro Ala Arg Ser Leu Gly Ala Ala225
230 235 240Val Ile Tyr Asn Lys Asp Lys
Ala Trp Asp Asp Gln Trp Ile Phe Trp 245
250 255Val Gly Pro Leu Ile Gly Ala Ala Ile Ala Ala Ala
Tyr His Gln Tyr 260 265 270Val
Leu Arg Ala Ser Ala Thr Lys Leu Gly Ser Tyr Arg Ser Asn Ala 275
280 28520285PRTZea mays 20Met Ala Lys Asp
Ile Glu Ala Ala Ala Ala His Glu Gly Lys Asp Tyr1 5
10 15Ser Asp Pro Pro Pro Ala Pro Leu Val Asp
Ala Glu Glu Leu Thr Lys 20 25
30Trp Ser Leu Tyr Arg Ala Val Ile Ala Glu Phe Val Ala Thr Leu Leu
35 40 45Phe Leu Tyr Ile Thr Val Ala Thr
Val Ile Gly Tyr Lys His Gln Thr 50 55
60Asp Ala Ala Ala Ser Gly Pro Asp Ala Ala Cys Gly Gly Val Gly Val65
70 75 80Leu Gly Ile Ala Trp
Ala Phe Gly Gly Met Ile Phe Ile Leu Val Tyr 85
90 95Cys Thr Ala Gly Val Ser Gly Gly His Ile Asn
Pro Ala Val Thr Phe 100 105
110Gly Leu Phe Leu Ala Arg Lys Val Ser Leu Val Arg Ala Leu Leu Tyr
115 120 125Ile Val Ala Gln Cys Leu Gly
Ala Ile Cys Gly Val Gly Leu Val Lys 130 135
140Gly Phe Gln Ser Ala Phe Tyr Val Arg Tyr Gly Gly Gly Ala Asn
Glu145 150 155 160Leu Ser
Ala Gly Tyr Ser Lys Gly Thr Gly Leu Ala Ala Glu Ile Ile
165 170 175Gly Thr Phe Val Leu Val Tyr
Thr Val Phe Ser Ala Thr Asp Pro Lys 180 185
190Arg Asn Ala Arg Asp Ser His Val Pro Val Leu Ala Pro Leu
Pro Ile 195 200 205Gly Phe Ala Val
Phe Met Val His Leu Ala Thr Ile Pro Ile Thr Gly 210
215 220Thr Gly Ile Asn Pro Ala Arg Ser Leu Gly Ala Ala
Val Ile Tyr Asn225 230 235
240Asn Asp Lys Ala Trp Asp Asp His Trp Ile Phe Trp Val Gly Pro Phe
245 250 255Ile Gly Ala Ala Ile
Ala Ala Ala Tyr His Gln Tyr Val Leu Arg Ala 260
265 270Ser Ala Ala Lys Leu Gly Ser Ser Ala Ser Phe Ser
Arg 275 280 28521288PRTZea mays
21Met Gly Lys Glu Val Asp Val Ser Thr Leu Glu Ala Gly Gly Val Arg1
5 10 15Asp Arg Asp Tyr Ala Asp
Pro Pro Pro Ala Pro Leu Ile Asp Ile Asp 20 25
30Glu Leu Gly Lys Trp Ser Leu Tyr Arg Ala Val Ile Ala
Glu Phe Val 35 40 45Ala Thr Leu
Leu Phe Leu Tyr Ile Thr Val Ala Thr Val Ile Gly Tyr 50
55 60Lys His Gln Thr Asp Ala Ser Ala Ser Gly Pro Asp
Ala Ala Cys Ser65 70 75
80Gly Val Gly Ile Leu Gly Ile Ala Trp Ala Phe Gly Gly Met Ile Phe
85 90 95Ile Leu Val Tyr Cys Thr
Ala Gly Ile Ser Gly Gly His Ile Asn Pro 100
105 110Ala Val Thr Phe Gly Leu Phe Leu Ala Arg Lys Val
Ser Leu Val Arg 115 120 125Ala Leu
Leu Tyr Met Ala Ala Gln Ser Leu Gly Ala Ile Cys Gly Val 130
135 140Ala Leu Val Lys Gly Phe Gln Ser Gly Phe Tyr
Ala Arg Tyr Gly Gly145 150 155
160Gly Ala Asn Glu Val Ser Ala Gly Tyr Ser Thr Gly Thr Gly Leu Ala
165 170 175Ala Glu Ile Ile
Gly Thr Phe Val Leu Val Tyr Thr Val Phe Ser Ala 180
185 190Thr Asp Pro Lys Arg Asn Ala Arg Asp Ser His
Val Pro Val Leu Ala 195 200 205Pro
Leu Pro Ile Gly Phe Ala Val Phe Met Val His Leu Ala Thr Ile 210
215 220Pro Ile Thr Gly Thr Gly Ile Asn Pro Ala
Arg Ser Leu Gly Ala Ala225 230 235
240Val Val Tyr Asn Asn Ser Lys Ala Trp Ser Asp Gln Trp Ile Phe
Trp 245 250 255Val Gly Pro
Phe Ile Gly Ala Ala Ile Ala Ala Leu Tyr His Gln Ile 260
265 270Val Leu Arg Ala Ser Ala Arg Gly Tyr Gly
Ser Phe Arg Ser Asn Ala 275 280
28522287PRTZea mays 22Met Ala Lys Asp Val Glu Gln Val Thr Glu Gln Gly Glu
Tyr Ser Ala1 5 10 15Lys
Asp Tyr His Asp Pro Pro Pro Ala Pro Leu Ile Asp Pro Asp Glu 20
25 30Leu Thr Lys Trp Ser Leu Tyr Arg
Ala Ala Ile Ala Glu Phe Ile Ala 35 40
45Thr Leu Leu Phe Leu Tyr Ile Thr Val Leu Thr Ile Ile Gly Tyr Lys
50 55 60Arg Gln Ser Asp Thr Lys Ile Pro
Gly Asn Thr Glu Cys Asp Gly Val65 70 75
80Gly Ile Leu Gly Ile Ala Trp Ala Phe Gly Gly Met Ile
Phe Ile Leu 85 90 95Val
Tyr Cys Thr Ala Gly Ile Ser Gly Gly His Ile Asn Pro Ala Val
100 105 110Thr Phe Gly Leu Phe Leu Gly
Arg Lys Val Ser Leu Val Arg Ala Leu 115 120
125Leu Tyr Met Ile Ala Gln Cys Ala Gly Ala Ile Cys Gly Ala Gly
Leu 130 135 140Ala Lys Gly Phe Gln Lys
Ser Phe Tyr Asn Arg Tyr Gly Gly Gly Val145 150
155 160Asn Thr Val Ser Asp Gly Tyr Asn Lys Gly Thr
Ala Leu Gly Ala Glu 165 170
175Ile Ile Gly Thr Phe Val Leu Val Tyr Thr Val Phe Ser Ala Thr Asp
180 185 190Pro Lys Arg Asn Ala Arg
Asp Ser His Val Pro Val Leu Ala Pro Leu 195 200
205Pro Ile Gly Phe Ala Val Phe Met Val His Leu Ala Thr Ile
Pro Val 210 215 220Thr Gly Thr Gly Ile
Asn Pro Ala Arg Ser Phe Gly Pro Ala Val Ile225 230
235 240Phe Asn Asn Asp Lys Ala Trp Asp Asp Gln
Trp Ile Tyr Trp Val Gly 245 250
255Pro Phe Val Gly Ala Ala Val Ala Ala Ile Tyr His Gln Tyr Ile Leu
260 265 270Arg Gly Ser Ala Ile
Lys Ala Leu Gly Ser Phe Arg Ser Asn Ala 275 280
28523287PRTArabidopsis thaliana 23Met Ala Lys Asp Val Glu
Ala Val Pro Gly Glu Gly Phe Gln Thr Arg1 5
10 15Asp Tyr Gln Asp Pro Pro Pro Ala Pro Phe Ile Asp
Gly Ala Glu Leu 20 25 30Lys
Lys Trp Ser Phe Tyr Arg Ala Val Ile Ala Glu Phe Val Ala Thr 35
40 45Leu Leu Phe Leu Tyr Ile Thr Val Leu
Thr Val Ile Gly Tyr Lys Ile 50 55
60Gln Ser Asp Thr Asp Ala Gly Gly Val Asp Cys Gly Gly Val Gly Ile65
70 75 80Leu Gly Ile Ala Trp
Ala Phe Gly Gly Met Ile Phe Ile Leu Val Tyr 85
90 95Cys Thr Ala Gly Ile Ser Gly Gly His Ile Asn
Pro Ala Val Thr Phe 100 105
110Gly Leu Phe Leu Ala Arg Lys Val Ser Leu Pro Arg Ala Leu Leu Tyr
115 120 125Ile Ile Ala Gln Cys Leu Gly
Ala Ile Cys Gly Val Gly Phe Val Lys 130 135
140Ala Phe Gln Ser Ser Tyr Tyr Thr Arg Tyr Gly Gly Gly Ala Asn
Ser145 150 155 160Leu Ala
Asp Gly Tyr Ser Thr Gly Thr Gly Leu Ala Ala Glu Ile Ile
165 170 175Gly Thr Phe Val Leu Val Tyr
Thr Val Phe Ser Ala Thr Asp Pro Lys 180 185
190Arg Ser Ala Arg Asp Ser His Val Pro Val Leu Ala Pro Leu
Pro Ile 195 200 205Gly Phe Ala Val
Phe Met Val His Leu Ala Thr Ile Pro Ile Thr Gly 210
215 220Thr Gly Ile Asn Pro Ala Arg Ser Phe Gly Ala Ala
Val Ile Tyr Asn225 230 235
240Lys Ser Lys Pro Trp Asp Asp His Trp Ile Phe Trp Val Gly Pro Phe
245 250 255Ile Gly Ala Ala Ile
Ala Ala Phe Tyr His Gln Phe Val Leu Arg Ala 260
265 270Ser Gly Ser Lys Ser Leu Gly Ser Phe Arg Ser Ala
Ala Asn Val 275 280
28524285PRTArabidopsis thaliana 24Met Ala Lys Asp Val Glu Gly Pro Glu Gly
Phe Gln Thr Arg Asp Tyr1 5 10
15Glu Asp Pro Pro Pro Thr Pro Phe Phe Asp Ala Asp Glu Leu Thr Lys
20 25 30Trp Ser Leu Tyr Arg Ala
Val Ile Ala Glu Phe Val Ala Thr Leu Leu 35 40
45Phe Leu Tyr Ile Thr Val Leu Thr Val Ile Gly Tyr Lys Ile
Gln Ser 50 55 60Asp Thr Lys Ala Gly
Gly Val Asp Cys Gly Gly Val Gly Ile Leu Gly65 70
75 80Ile Ala Trp Ala Phe Gly Gly Met Ile Phe
Ile Leu Val Tyr Cys Thr 85 90
95Ala Gly Ile Ser Gly Gly His Ile Asn Pro Ala Val Thr Phe Gly Leu
100 105 110Phe Leu Ala Arg Lys
Val Ser Leu Ile Arg Ala Val Leu Tyr Met Val 115
120 125Ala Gln Cys Leu Gly Ala Ile Cys Gly Val Gly Phe
Val Lys Ala Phe 130 135 140Gln Ser Ser
Tyr Tyr Asp Arg Tyr Gly Gly Gly Ala Asn Ser Leu Ala145
150 155 160Asp Gly Tyr Asn Thr Gly Thr
Gly Leu Ala Ala Glu Ile Ile Gly Thr 165
170 175Phe Val Leu Val Tyr Thr Val Phe Ser Ala Thr Asp
Pro Lys Arg Asn 180 185 190Ala
Arg Asp Ser His Val Pro Val Leu Ala Pro Leu Pro Ile Gly Phe 195
200 205Ala Val Phe Met Val His Leu Ala Thr
Ile Pro Ile Thr Gly Thr Gly 210 215
220Ile Asn Pro Ala Arg Ser Phe Gly Ala Ala Val Ile Tyr Asn Lys Ser225
230 235 240Lys Pro Trp Asp
Asp His Trp Ile Phe Trp Val Gly Pro Phe Ile Gly 245
250 255Ala Ala Ile Ala Ala Phe Tyr His Gln Phe
Val Leu Arg Ala Ser Gly 260 265
270Ser Lys Ser Leu Gly Ser Phe Arg Ser Ala Ala Asn Val 275
280 28525285PRTArabidopsis thaliana 25Met Ala
Lys Asp Val Glu Gly Pro Asp Gly Phe Gln Thr Arg Asp Tyr1 5
10 15Glu Asp Pro Pro Pro Thr Pro Phe
Phe Asp Ala Glu Glu Leu Thr Lys 20 25
30Trp Ser Leu Tyr Arg Ala Val Ile Ala Glu Phe Val Ala Thr Leu
Leu 35 40 45Phe Leu Tyr Val Thr
Val Leu Thr Val Ile Gly Tyr Lys Ile Gln Ser 50 55
60Asp Thr Lys Ala Gly Gly Val Asp Cys Gly Gly Val Gly Ile
Leu Gly65 70 75 80Ile
Ala Trp Ala Phe Gly Gly Met Ile Phe Ile Leu Val Tyr Cys Thr
85 90 95Ala Gly Ile Ser Gly Gly His
Ile Asn Pro Ala Val Thr Phe Gly Leu 100 105
110Phe Leu Ala Arg Lys Val Ser Leu Ile Arg Ala Val Leu Tyr
Met Val 115 120 125Ala Gln Cys Leu
Gly Ala Ile Cys Gly Val Gly Phe Val Lys Ala Phe 130
135 140Gln Ser Ser His Tyr Val Asn Tyr Gly Gly Gly Ala
Asn Phe Leu Ala145 150 155
160Asp Gly Tyr Asn Thr Gly Thr Gly Leu Ala Ala Glu Ile Ile Gly Thr
165 170 175Phe Val Leu Val Tyr
Thr Val Phe Ser Ala Thr Asp Pro Lys Arg Asn 180
185 190Ala Arg Asp Ser His Val Pro Val Leu Ala Pro Leu
Pro Ile Gly Phe 195 200 205Ala Val
Phe Met Val His Leu Ala Thr Ile Pro Ile Thr Gly Thr Gly 210
215 220Ile Asn Pro Ala Arg Ser Phe Gly Ala Ala Val
Ile Phe Asn Lys Ser225 230 235
240Lys Pro Trp Asp Asp His Trp Ile Phe Trp Val Gly Pro Phe Ile Gly
245 250 255Ala Thr Ile Ala
Ala Phe Tyr His Gln Phe Val Leu Arg Ala Ser Gly 260
265 270Ser Lys Ser Leu Gly Ser Phe Arg Ser Ala Ala
Asn Val 275 280
28526291PRTArabidopsis thaliana 26Met Ala Lys Asp Leu Asp Val Asn Glu Ser
Gly Pro Pro Ala Ala Arg1 5 10
15Asp Tyr Lys Asp Pro Pro Pro Ala Pro Phe Phe Asp Met Glu Glu Leu
20 25 30Arg Lys Trp Pro Leu Tyr
Arg Ala Val Ile Ala Glu Phe Val Ala Thr 35 40
45Leu Leu Phe Leu Tyr Val Ser Ile Leu Thr Val Ile Gly Tyr
Lys Ala 50 55 60Gln Thr Asp Ala Thr
Ala Gly Gly Val Asp Cys Gly Gly Val Gly Ile65 70
75 80Leu Gly Ile Ala Trp Ala Phe Gly Gly Met
Ile Phe Val Leu Val Tyr 85 90
95Cys Thr Ala Gly Ile Ser Gly Gly His Ile Asn Pro Ala Val Thr Val
100 105 110Gly Leu Phe Leu Ala
Arg Lys Val Ser Leu Val Arg Thr Val Leu Tyr 115
120 125Ile Val Ala Gln Cys Leu Gly Ala Ile Cys Gly Cys
Gly Phe Val Lys 130 135 140Ala Phe Gln
Ser Ser Tyr Tyr Thr Arg Tyr Gly Gly Gly Ala Asn Glu145
150 155 160Leu Ala Asp Gly Tyr Asn Lys
Gly Thr Gly Leu Gly Ala Glu Ile Ile 165
170 175Gly Thr Phe Val Leu Val Tyr Thr Val Phe Ser Ala
Thr Asp Pro Lys 180 185 190Arg
Asn Ala Arg Asp Ser His Val Pro Val Leu Ala Pro Leu Pro Ile 195
200 205Gly Phe Ala Val Phe Met Val His Leu
Ala Thr Ile Pro Ile Thr Gly 210 215
220Thr Gly Ile Asn Pro Ala Arg Ser Phe Gly Ala Ala Val Ile Tyr Asn225
230 235 240Asn Glu Lys Ala
Trp Asp Asp Gln Trp Ile Phe Trp Val Gly Pro Met 245
250 255Ile Gly Ala Ala Ala Ala Ala Phe Tyr His
Gln Phe Ile Leu Arg Ala 260 265
270Ala Ala Ile Lys Ala Leu Gly Ser Phe Gly Ser Phe Gly Ser Phe Arg
275 280 285Ser Phe Ala
29027286PRTArabidopsis thaliana 27Met Thr Lys Glu Val Val Gly Asp Lys Arg
Ser Phe Ser Gly Lys Asp1 5 10
15Tyr Gln Asp Pro Pro Pro Glu Pro Leu Phe Asp Ala Thr Glu Leu Gly
20 25 30Lys Trp Ser Phe Tyr Arg
Ala Leu Ile Ala Glu Phe Ile Ala Thr Leu 35 40
45Leu Phe Leu Tyr Val Thr Ile Met Thr Val Ile Gly Tyr Lys
Ser Gln 50 55 60Thr Asp Pro Ala Leu
Asn Pro Asp Gln Cys Thr Gly Val Gly Val Leu65 70
75 80Gly Ile Ala Trp Ala Phe Gly Gly Met Ile
Phe Ile Leu Val Tyr Cys 85 90
95Thr Ala Gly Ile Ser Gly Gly His Ile Asn Pro Ala Val Thr Phe Gly
100 105 110Leu Leu Leu Ala Arg
Lys Val Thr Leu Val Arg Ala Val Met Tyr Met 115
120 125Val Ala Gln Cys Leu Gly Ala Ile Cys Gly Val Ala
Leu Val Lys Ala 130 135 140Phe Gln Ser
Ala Tyr Phe Thr Arg Tyr Gly Gly Gly Ala Asn Gly Leu145
150 155 160Ser Asp Gly Tyr Ser Ile Gly
Thr Gly Val Ala Ala Glu Ile Ile Gly 165
170 175Thr Phe Val Leu Val Tyr Thr Val Phe Ser Ala Thr
Asp Pro Lys Arg 180 185 190Ser
Ala Arg Asp Ser His Val Pro Val Leu Ala Pro Leu Pro Ile Gly 195
200 205Phe Ala Val Phe Ile Val His Leu Ala
Thr Ile Pro Ile Thr Gly Thr 210 215
220Gly Ile Asn Pro Ala Arg Ser Leu Gly Ala Ala Ile Ile Tyr Asn Lys225
230 235 240Asp Lys Ala Trp
Asp His His Trp Ile Phe Trp Val Gly Pro Phe Ala 245
250 255Gly Ala Ala Ile Ala Ala Phe Tyr His Gln
Phe Val Leu Arg Ala Gly 260 265
270Ala Ile Lys Ala Leu Gly Ser Phe Arg Ser Gln Pro His Val 275
280 28528289PRTArabidopsis thaliana 28Met
Thr Lys Asp Glu Leu Thr Glu Glu Glu Ser Leu Ser Gly Lys Asp1
5 10 15Tyr Leu Asp Pro Pro Pro Val
Lys Thr Phe Glu Val Arg Glu Leu Lys 20 25
30Lys Trp Ser Phe Tyr Arg Ala Val Ile Ala Glu Phe Ile Ala
Thr Leu 35 40 45Leu Phe Leu Tyr
Val Thr Val Leu Thr Val Ile Gly Phe Lys Ser Gln 50 55
60Thr Asp Ile Asn Ala Gly Gly Gly Ala Cys Ala Ser Val
Gly Leu Leu65 70 75
80Gly Ile Ser Trp Ala Phe Gly Gly Met Ile Phe Ile Leu Val Tyr Cys
85 90 95Thr Ala Gly Ile Ser Gly
Gly His Ile Asn Pro Ala Val Thr Phe Gly 100
105 110Leu Phe Leu Ala Ser Lys Val Ser Leu Val Arg Ala
Val Ser Tyr Met 115 120 125Val Ala
Gln Cys Leu Gly Ala Thr Cys Gly Val Gly Leu Val Lys Val 130
135 140Phe Gln Ser Thr Tyr Tyr Asn Arg Tyr Gly Gly
Gly Ala Asn Met Leu145 150 155
160Ser Asp Gly Tyr Asn Val Gly Val Gly Val Gly Ala Glu Ile Ile Gly
165 170 175Thr Phe Val Leu
Val Tyr Thr Val Phe Ser Ala Thr Asp Pro Lys Arg 180
185 190Asn Ala Arg Asp Ser His Ile Pro Val Leu Ala
Pro Leu Pro Ile Gly 195 200 205Phe
Ser Val Phe Met Val His Leu Ala Thr Ile Pro Ile Thr Gly Thr 210
215 220Gly Ile Asn Pro Ala Arg Ser Phe Gly Ala
Ala Val Ile Tyr Asn Asn225 230 235
240Gln Lys Ala Trp Asp Asp Gln Trp Ile Phe Trp Val Gly Pro Phe
Val 245 250 255Gly Ala Ala
Ile Ala Ala Phe Tyr His Gln Phe Val Leu Arg Ala Gly 260
265 270Ala Met Lys Ala Tyr Gly Ser Val Arg Ser
Gln Leu His Glu Leu His 275 280
285Ala 29280PRTArabidopsis thaliana 29Met Ser Lys Glu Val Ser Glu Glu Gly
Lys Thr His His Gly Lys Asp1 5 10
15Tyr Val Asp Pro Pro Pro Ala Pro Leu Leu Asp Met Gly Glu Leu
Lys 20 25 30Ser Trp Ser Phe
Tyr Arg Ala Leu Ile Ala Glu Phe Ile Ala Thr Leu 35
40 45Leu Phe Leu Tyr Val Thr Val Ala Thr Val Ile Gly
His Lys Lys Gln 50 55 60Thr Gly Pro
Cys Asp Gly Val Gly Leu Leu Gly Ile Ala Trp Ala Phe65 70
75 80Gly Gly Met Ile Phe Val Leu Val
Tyr Cys Thr Ala Gly Ile Ser Gly 85 90
95Gly His Ile Asn Pro Ala Val Thr Phe Gly Leu Phe Leu Ala
Arg Lys 100 105 110Val Ser Leu
Val Arg Ala Leu Gly Tyr Met Ile Ala Gln Cys Leu Gly 115
120 125Ala Ile Cys Gly Val Gly Phe Val Lys Ala Phe
Met Lys Thr Pro Tyr 130 135 140Asn Thr
Leu Gly Gly Gly Ala Asn Thr Val Ala Asp Gly Tyr Ser Lys145
150 155 160Gly Thr Ala Leu Gly Ala Glu
Ile Ile Gly Thr Phe Val Leu Val Tyr 165
170 175Thr Val Phe Ser Ala Thr Asp Pro Lys Arg Ser Ala
Arg Asp Ser His 180 185 190Ile
Pro Val Leu Ala Pro Leu Pro Ile Gly Phe Ala Val Phe Met Val 195
200 205His Leu Ala Thr Ile Pro Ile Thr Gly
Thr Gly Ile Asn Pro Ala Arg 210 215
220Ser Phe Gly Ala Ala Val Ile Tyr Asn Asn Glu Lys Ala Trp Asp Asp225
230 235 240Gln Trp Ile Phe
Trp Val Gly Pro Phe Leu Gly Ala Leu Ala Ala Ala 245
250 255Ala Tyr His Gln Tyr Ile Leu Arg Ala Ser
Ala Ile Lys Ala Leu Gly 260 265
270Ser Phe Arg Ser Asn Ala Thr Asn 275
28030278PRTArabidopsis thaliana 30Met Ser Lys Glu Val Ser Glu Glu Gly Arg
His Gly Lys Asp Tyr Val1 5 10
15Asp Pro Pro Pro Ala Pro Leu Leu Asp Met Ala Glu Leu Lys Leu Trp
20 25 30Ser Phe Tyr Arg Ala Ile
Ile Ala Glu Phe Ile Ala Thr Leu Leu Phe 35 40
45Leu Tyr Val Thr Val Ala Thr Val Ile Gly His Lys Asn Gln
Thr Gly 50 55 60Pro Cys Gly Gly Val
Gly Leu Leu Gly Ile Ala Trp Ala Phe Gly Gly65 70
75 80Met Ile Phe Val Leu Val Tyr Cys Thr Ala
Gly Ile Ser Gly Gly His 85 90
95Ile Asn Pro Ala Val Thr Phe Gly Leu Phe Leu Ala Arg Lys Val Ser
100 105 110Leu Pro Arg Ala Val
Ala Tyr Met Val Ala Gln Cys Leu Gly Ala Ile 115
120 125Cys Gly Val Gly Leu Val Lys Ala Phe Met Met Thr
Pro Tyr Lys Arg 130 135 140Leu Gly Gly
Gly Ala Asn Thr Val Ala Asp Gly Tyr Ser Thr Gly Thr145
150 155 160Ala Leu Gly Ala Glu Ile Ile
Gly Thr Phe Val Leu Val Tyr Thr Val 165
170 175Phe Ser Ala Thr Asp Pro Lys Arg Ser Ala Arg Asp
Ser His Val Pro 180 185 190Val
Leu Ala Pro Leu Pro Ile Gly Phe Ala Val Phe Met Val His Leu 195
200 205Ala Thr Ile Pro Ile Thr Gly Thr Gly
Ile Asn Pro Ala Arg Ser Phe 210 215
220Gly Ala Ala Val Ile Tyr Asn Asn Glu Lys Ala Trp Asp Asp His Trp225
230 235 240Ile Phe Trp Val
Gly Pro Phe Val Gly Ala Leu Ala Ala Ala Ala Tyr 245
250 255His Gln Tyr Ile Leu Arg Ala Ala Ala Ile
Lys Ala Leu Ala Ser Phe 260 265
270Arg Ser Asn Pro Thr Asn 27531309PRTPicea abies 31Met Thr Lys
Glu Glu Arg Arg Glu Ser Glu Gln Gln Gly Phe Pro Pro1 5
10 15Lys Asp Tyr Thr Asp Pro Pro Pro Ala
Ala Leu Ile Glu Thr Ser Glu 20 25
30Phe Lys Leu Trp Ser Phe Tyr Arg Ala Leu Ile Ala Glu Phe Val Ala
35 40 45Thr Leu Leu Phe Leu Tyr Ile
Thr Ile Ala Thr Val Ile Gly His Ser 50 55
60Arg Thr Ser Thr Asn Cys Gly Ser Val Gly Val Leu Gly Ile Ala Trp65
70 75 80Ser Phe Gly Gly
Met Ile Phe Val Leu Val Tyr Cys Thr Ala Gly Ile 85
90 95Ser Gly Gly His Ile Asn Pro Ala Val Thr
Phe Gly Leu Phe Leu Ala 100 105
110Arg Lys Val Ser Leu Pro Arg Ala Ile Leu Tyr Met Ile Ala Gln Cys
115 120 125Leu Gly Ala Ile Cys Gly Thr
Gly Leu Ala Ile Cys Gly Thr Gly Leu 130 135
140Val Lys Ser Phe Gln Lys Ser Phe Tyr Asp Arg Tyr Gly Gly Gly
Ala145 150 155 160Asn Tyr
Val His His Gly Tyr Thr Lys Gly Val Gly Leu Ala Ala Glu
165 170 175Ile Ile Gly Thr Phe Val Leu
Val Tyr Thr Val Phe Ser Ala Thr Asp 180 185
190Pro Lys Arg Ser Ala Arg Asp Ser His Val Pro Val Leu Ala
Pro Leu 195 200 205Pro Ile Gly Phe
Ala Val Phe Met Val His Leu Ala Thr Ile Pro Ile 210
215 220Thr Gly Thr Gly Ile Asn Pro Ala Arg Ser Phe Gly
Ala Ala Val Ile225 230 235
240Tyr Gly His Lys Gln Ser Trp Asp Asp His Trp Ile Phe Trp Val Gly
245 250 255Pro Phe Ala Gly Ala
Ala Leu Ala Ala Ala Tyr His Gln Tyr Ile Leu 260
265 270Arg Ala Ala Ala Ile Lys Ala Leu Gly Ser Phe Arg
Ser Asn Gly Asn 275 280 285Val Glu
Leu Glu Glu Leu Val Ala Arg Arg Ser Cys Leu Cys Leu Lys 290
295 300Tyr Val Gly Leu Gln30532279PRTPhyscomitrella
patens 32Met Ala Lys Asp Val Gly Val Glu Pro Gly Phe Pro Ser Lys Asp Tyr1
5 10 15Thr Asp Pro Pro
Pro Ala Pro Leu Ile Asp Ala Ser Glu Phe Gly Gln 20
25 30Trp Ser Phe Tyr Arg Ala Val Ile Ala Glu Phe
Val Ala Thr Leu Leu 35 40 45Phe
Leu Tyr Ile Thr Ile Ala Thr Val Ile Gly Ala Val Arg Asn Ala 50
55 60Gly Cys Asp Gly Val Gly Leu Leu Gly Ile
Ala Trp Ala Phe Gly Gly65 70 75
80Met Ile Phe Val Leu Val Tyr Cys Thr Ala Gly Ile Ser Gly Gly
His 85 90 95Ile Asn Pro
Ala Val Thr Phe Gly Leu Leu Leu Ala Arg Lys Ile Ser 100
105 110Leu Pro Arg Ala Leu Ala Tyr Met Ile Ala
Gln Cys Leu Gly Ala Ile 115 120
125Cys Gly Ala Gly Leu Val Lys Gly Phe Gln Thr Ala Phe Tyr Met Arg 130
135 140Tyr Gly Gly Gly Ala Asn Ser Val
Ala Ala Gly Tyr Ser Ile Gly Thr145 150
155 160Gly Leu Ala Ala Glu Ile Ile Gly Thr Phe Val Leu
Val Tyr Thr Val 165 170
175Phe Ser Ala Thr Asp Pro Lys Arg Asn Ala Arg Asp Ser His Val Pro
180 185 190Val Leu Ala Pro Leu Pro
Ile Gly Phe Ala Val Phe Met Val His Leu 195 200
205Ala Thr Ile Pro Ile Thr Gly Thr Gly Ile Asn Pro Ala Arg
Ser Phe 210 215 220Gly Ala Ala Val Ile
Tyr Asn Arg Ser Lys Pro Trp Asp Asp His Trp225 230
235 240Ile Phe Trp Val Gly Pro Phe Val Gly Ala
Ala Leu Ala Ala Ala Tyr 245 250
255His Gln Tyr Val Leu Arg Ala Gly Pro Phe Lys Gln Leu Gly Ser Phe
260 265 270Arg Ser Ala Pro Ser
Arg Val 27533281PRTSpinacia oleracea 33Met Ser Lys Glu Val Ser Glu
Glu Ala Gln Ala His Gln His Gly Lys1 5 10
15Asp Tyr Val Asp Pro Pro Pro Ala Pro Phe Phe Asp Leu
Gly Glu Leu 20 25 30Lys Leu
Trp Ser Phe Trp Arg Ala Ala Ile Ala Glu Phe Ile Ala Thr 35
40 45Leu Leu Phe Leu Tyr Ile Thr Val Ala Thr
Val Ile Gly His Ser Lys 50 55 60Glu
Thr Val Val Cys Gly Ser Val Gly Leu Leu Gly Ile Ala Trp Ala65
70 75 80Phe Gly Gly Met Ile Phe
Val Leu Val Tyr Cys Thr Ala Gly Ile Ser 85
90 95Gly Gly His Ile Asn Pro Ala Val Thr Phe Gly Leu
Phe Leu Ala Arg 100 105 110Lys
Val Ser Leu Leu Arg Ala Leu Val Tyr Met Ile Ala Gln Cys Leu 115
120 125Gly Ala Ile Cys Gly Val Gly Leu Val
Lys Ala Phe Met Lys Gly Pro 130 135
140Tyr Asn Gln Phe Gly Gly Gly Ala Asn Ser Val Ala Leu Gly Tyr Asn145
150 155 160Lys Gly Thr Ala
Leu Gly Ala Glu Ile Ile Gly Thr Phe Val Leu Val 165
170 175Tyr Thr Val Phe Ser Ala Thr Asp Pro Lys
Arg Ser Ala Arg Asp Ser 180 185
190His Val Pro Ile Leu Ala Pro Leu Pro Ile Gly Phe Ala Val Phe Met
195 200 205Val His Leu Ala Thr Ile Pro
Ile Thr Gly Thr Gly Ile Asn Pro Ala 210 215
220Arg Ser Phe Gly Ala Ala Val Ile Phe Asn Ser Asn Lys Val Trp
Asp225 230 235 240Asp Gln
Trp Ile Phe Trp Val Gly Pro Phe Ile Gly Ala Ala Val Ala
245 250 255Ala Ala Tyr His Gln Tyr Val
Leu Arg Ala Ala Ala Ile Lys Ala Leu 260 265
270Gly Ser Phe Arg Ser Asn Pro Thr Asn 275
28034263PRTHomo sapiens 34Met Trp Glu Leu Arg Ser Ala Ser Phe Trp
Arg Ala Ile Phe Ala Glu1 5 10
15Phe Phe Ala Thr Leu Phe Tyr Val Phe Phe Gly Leu Gly Ser Ser Leu
20 25 30Arg Trp Ala Pro Gly Pro
Leu His Val Leu Gln Val Ala Met Ala Phe 35 40
45Gly Leu Ala Leu Ala Thr Leu Val Gln Ser Val Gly His Ile
Ser Gly 50 55 60Ala His Val Asn Pro
Ala Val Thr Phe Ala Phe Leu Val Gly Ser Gln65 70
75 80Met Ser Leu Leu Arg Ala Phe Cys Tyr Met
Ala Ala Gln Leu Leu Gly 85 90
95Ala Val Ala Gly Ala Ala Val Leu Tyr Ser Val Thr Pro Pro Ala Val
100 105 110Arg Gly Asn Leu Ala
Leu Asn Thr Leu His Pro Ala Val Ser Val Gly 115
120 125Gln Ala Thr Thr Val Glu Ile Phe Leu Thr Leu Gln
Phe Val Leu Cys 130 135 140Ile Phe Ala
Thr Tyr Asp Glu Arg Arg Asn Gly Gln Leu Gly Ser Val145
150 155 160Ala Leu Ala Val Gly Phe Ser
Leu Ala Leu Gly His Leu Phe Gly Met 165
170 175Tyr Tyr Thr Gly Ala Gly Met Asn Pro Ala Arg Ser
Phe Ala Pro Ala 180 185 190Ile
Leu Thr Gly Asn Phe Thr Asn His Trp Val Tyr Trp Val Gly Pro 195
200 205Ile Ile Gly Gly Gly Leu Gly Ser Leu
Leu Tyr Asp Phe Leu Leu Phe 210 215
220Pro Arg Leu Lys Ser Ile Ser Glu Arg Leu Ser Val Leu Lys Gly Ala225
230 235 240Lys Pro Asp Val
Ser Asn Gly Gln Pro Glu Val Thr Gly Glu Pro Val 245
250 255Glu Leu Asn Thr Gln Ala Leu
26035263PRTBos taurus 35Met Trp Glu Leu Arg Ser Ala Ser Phe Trp Arg Ala
Ile Cys Ala Glu1 5 10
15Phe Phe Ala Ser Leu Phe Tyr Val Phe Phe Gly Leu Gly Ala Ser Leu
20 25 30Arg Trp Ala Pro Gly Pro Leu
His Val Leu Gln Val Ala Leu Ala Phe 35 40
45Gly Leu Ala Leu Ala Thr Leu Val Gln Ala Val Gly His Ile Ser
Gly 50 55 60Ala His Val Asn Pro Ala
Val Thr Phe Ala Phe Leu Val Gly Ser Gln65 70
75 80Met Ser Leu Leu Arg Ala Ile Cys Tyr Met Val
Ala Gln Leu Leu Gly 85 90
95Ala Val Ala Gly Ala Ala Val Leu Tyr Ser Val Thr Pro Pro Ala Val
100 105 110Arg Gly Asn Leu Ala Leu
Asn Thr Leu His Pro Gly Val Ser Val Gly 115 120
125Gln Ala Thr Ile Val Glu Ile Phe Leu Thr Leu Gln Phe Val
Leu Cys 130 135 140Ile Phe Ala Thr Tyr
Asp Glu Arg Arg Asn Gly Arg Leu Gly Ser Val145 150
155 160Ala Leu Ala Val Gly Phe Ser Leu Thr Leu
Gly His Leu Phe Gly Met 165 170
175Tyr Tyr Thr Gly Ala Gly Met Asn Pro Ala Arg Ser Phe Ala Pro Ala
180 185 190Ile Leu Thr Arg Asn
Phe Thr Asn His Trp Val Tyr Trp Val Gly Pro 195
200 205Val Ile Gly Ala Gly Leu Gly Ser Leu Leu Tyr Asp
Phe Leu Leu Phe 210 215 220Pro Arg Leu
Lys Ser Val Ser Glu Arg Leu Ser Ile Leu Lys Gly Ser225
230 235 240Arg Pro Ser Glu Ser Asn Gly
Gln Pro Glu Val Thr Gly Glu Pro Val 245
250 255Glu Leu Lys Thr Gln Ala Leu
26036262PRTGallus gallus 36Met Arg Glu Leu Arg Ser Ser Ser Phe Trp Arg
Ala Ile Leu Ala Glu1 5 10
15Phe Leu Gly Ser Leu Leu Tyr Thr Leu Leu Gly Leu Gly Ala Ser Leu
20 25 30Arg Trp Ala Pro Gly Pro His
Gly Val Leu Gly Ser Ala Leu Ala Phe 35 40
45Gly Leu Ala Gln Ala Thr Leu Val Gln Ala Leu Gly His Val Ser
Gly 50 55 60Gly His Ile Asn Pro Ala
Ile Thr Leu Ala Phe Leu Leu Ala Ser Gln65 70
75 80Leu Ser Leu Pro Arg Ala Leu Gly Tyr Leu Leu
Ala Gln Leu Leu Gly 85 90
95Ala Leu Ala Gly Ala Gly Val Leu Tyr Gly Val Thr Pro Ala Ala Val
100 105 110Arg Gly Thr Leu Gly Leu
Ser Ala Leu His Pro Ser Val Gly Pro Gly 115 120
125Gln Gly Thr Val Val Glu Leu Leu Leu Thr Ala Gln Phe Ile
Leu Cys 130 135 140Val Phe Ala Ser Phe
Asp Asp Arg His Asp Gly Arg Pro Gly Ser Ala145 150
155 160Ala Leu Pro Val Gly Phe Ser Leu Ala Leu
Gly His Leu Phe Gly Ile 165 170
175Pro Phe Thr Gly Ala Gly Met Asn Pro Ala Arg Ser Phe Ala Pro Ala
180 185 190Val Ile Thr Arg Asn
Phe Thr Asn His Trp Val Phe Trp Ala Gly Pro 195
200 205Leu Leu Gly Ala Ala Leu Ala Ala Leu Leu Tyr Glu
Leu Ala Leu Cys 210 215 220Pro Arg Ala
Arg Ser Met Ala Glu Arg Leu Ala Val Leu Arg Gly Glu225
230 235 240Pro Pro Ala Ala Ala Pro Pro
Pro Glu Pro Pro Ala Glu Pro Leu Glu 245
250 255Leu Lys Thr Gln Gly Leu
26037262PRTXenopus laevis 37Trp Glu Phe Arg Ser Phe Ser Phe Trp Arg Ala
Val Phe Ala Glu Phe1 5 10
15Phe Gly Thr Met Phe Tyr Val Phe Phe Gly Leu Gly Ala Ser Leu Lys
20 25 30Trp Ala Ala Gly Pro Ala Asn
Val Leu Val Ile Ala Leu Ala Phe Gly 35 40
45Leu Val Leu Ala Thr Met Val Gln Ser Ile Gly His Val Ser Gly
Ala 50 55 60His Ile Asn Pro Ala Val
Thr Phe Ala Phe Leu Ile Gly Ser Gln Met65 70
75 80Ser Leu Phe Arg Ala Ile Phe Tyr Ile Ala Ala
Gln Leu Leu Gly Ala 85 90
95Val Ala Gly Ala Ala Val Leu Tyr Gly Val Thr Pro Ala Ala Ile Arg
100 105 110Gly Asn Leu Ala Leu Asn
Thr Leu His Pro Gly Val Ser Leu Gly Gln 115 120
125Ala Thr Thr Val Glu Ile Phe Leu Thr Leu Gln Phe Val Leu
Cys Ile 130 135 140Phe Ala Thr Tyr Asp
Glu Arg Arg Asn Gly Arg Leu Gly Ser Val Ser145 150
155 160Leu Ala Ile Gly Phe Ser Leu Thr Leu Gly
His Leu Phe Gly Leu Tyr 165 170
175Tyr Thr Gly Ala Ser Met Asn Pro Ala Arg Ser Phe Ala Pro Ala Val
180 185 190Leu Thr Arg Asn Phe
Thr Asn His Trp Val Tyr Trp Val Gly Pro Ile 195
200 205Ile Gly Gly Ala Leu Gly Gly Leu Val Tyr Asp Phe
Ile Leu Phe Pro 210 215 220Arg Met Arg
Gly Leu Ser Glu Arg Leu Ser Ile Leu Lys Gly Ala Arg225
230 235 240Pro Ala Glu Pro Glu Gly Gln
Gln Glu Ala Thr Gly Glu Pro Ile Glu 245
250 255Leu Lys Thr Gln Ser Leu 26038271PRTBos
taurus 38Met Ala Ser Glu Phe Lys Lys Lys Leu Phe Trp Arg Ala Val Val Ala1
5 10 15Glu Phe Leu Ala
Met Ile Leu Phe Ile Phe Ile Ser Ile Gly Ser Ala 20
25 30Leu Gly Phe His Tyr Pro Ile Lys Ser Asn Gln
Thr Thr Gly Ala Val 35 40 45Gln
Asp Asn Val Lys Val Ser Leu Ala Phe Gly Leu Ser Ile Ala Thr 50
55 60Leu Ala Gln Ser Val Gly His Ile Ser Gly
Ala His Leu Asn Pro Ala65 70 75
80Val Thr Leu Gly Leu Leu Leu Ser Cys Gln Ile Ser Val Leu Arg
Ala 85 90 95Ile Met Tyr
Ile Ile Ala Gln Cys Val Gly Ala Ile Val Ala Thr Ala 100
105 110Ile Leu Ser Gly Ile Thr Ser Ser Leu Pro
Asp Asn Ser Leu Gly Leu 115 120
125Asn Ala Leu Ala Pro Gly Val Asn Ser Gly Gln Gly Leu Gly Ile Glu 130
135 140Ile Ile Gly Thr Leu Gln Leu Val
Leu Cys Val Leu Ala Thr Thr Asp145 150
155 160Arg Arg Arg Arg Asp Leu Gly Gly Ser Gly Pro Leu
Ala Ile Gly Phe 165 170
175Ser Val Ala Leu Gly His Leu Leu Ala Ile Asp Tyr Thr Gly Cys Gly
180 185 190Ile Asn Pro Ala Arg Ser
Phe Gly Ser Ser Val Ile Thr His Asn Phe 195 200
205Gln Asp His Trp Ile Phe Trp Val Gly Pro Phe Ile Gly Ala
Ala Leu 210 215 220Ala Val Leu Ile Tyr
Asp Phe Ile Leu Ala Pro Arg Ser Ser Asp Leu225 230
235 240Thr Asp Arg Val Lys Val Trp Thr Ser Gly
Gln Val Glu Glu Tyr Asp 245 250
255Leu Asp Ala Asp Asp Ile Asn Ser Arg Val Glu Met Lys Pro Lys
260 265 27039269PRTHomo sapiens
39Met Ala Ser Glu Phe Lys Lys Lys Leu Phe Trp Arg Ala Val Val Ala1
5 10 15Glu Phe Leu Ala Thr Thr
Leu Phe Val Phe Ile Ser Ile Gly Ser Ala 20 25
30Leu Gly Phe Lys Tyr Pro Val Gly Asn Asn Gln Thr Thr
Val Gln Asp 35 40 45Asn Val Lys
Val Ser Leu Ala Phe Gly Leu Ser Ile Ala Thr Leu Ala 50
55 60Gln Ser Val Gly His Ile Ser Gly Ala His Leu Asn
Pro Ala Val Thr65 70 75
80Leu Gly Leu Leu Leu Ser Cys Gln Ile Ser Ile Phe Arg Ala Leu Met
85 90 95Tyr Ile Ile Ala Gln Cys
Val Gly Ala Ile Val Ala Thr Ala Ile Leu 100
105 110Ser Gly Ile Thr Ser Ser Leu Thr Gly Asn Ser Leu
Gly Arg Asn Asp 115 120 125Leu Ala
Asp Gly Val Asn Ser Gly Gln Gly Leu Gly Ile Glu Ile Ile 130
135 140Gly Thr Leu Gln Leu Val Leu Cys Val Leu Ala
Thr Thr Asp Arg Arg145 150 155
160Arg Arg Asp Leu Gly Gly Ser Ala Pro Leu Ala Ile Gly Leu Ser Val
165 170 175Ala Leu Gly His
Leu Leu Ala Ile Asp Tyr Thr Gly Cys Gly Ile Asn 180
185 190Pro Ala Arg Ser Phe Gly Ser Ala Val Ile Thr
His Asn Phe Ser Asn 195 200 205His
Trp Ile Phe Trp Val Gly Pro Phe Ile Gly Gly Ala Leu Ala Val 210
215 220Leu Ile Tyr Asp Phe Ile Leu Ala Pro Arg
Ser Ser Asp Leu Thr Asp225 230 235
240Arg Val Lys Val Trp Thr Ser Gly Gln Val Glu Glu Tyr Asp Leu
Asp 245 250 255Ala Asp Asp
Ile Asn Ser Arg Val Glu Met Lys Pro Lys 260
26540271PRTHomo sapiens 40Met Trp Glu Leu Arg Ser Ile Ala Phe Ser Arg Ala
Val Phe Ala Glu1 5 10
15Phe Leu Ala Thr Leu Leu Phe Val Phe Phe Gly Leu Gly Ser Ala Leu
20 25 30Asn Trp Pro Gln Ala Leu Pro
Ser Val Leu Gln Ile Ala Met Ala Phe 35 40
45Gly Leu Gly Ile Gly Thr Leu Val Gln Ala Leu Gly His Ile Ser
Gly 50 55 60Ala His Ile Asn Pro Ala
Val Thr Val Ala Cys Leu Val Gly Cys His65 70
75 80Val Ser Val Leu Arg Ala Ala Phe Tyr Val Ala
Ala Gln Leu Leu Gly 85 90
95Ala Val Ala Gly Ala Ala Leu Leu His Glu Ile Thr Pro Ala Asp Ile
100 105 110Arg Gly Asp Leu Ala Val
Asn Ala Leu Ser Asn Ser Thr Thr Ala Gly 115 120
125Gln Ala Val Thr Val Glu Leu Phe Leu Thr Leu Gln Leu Val
Leu Cys 130 135 140Ile Phe Ala Ser Thr
Asp Glu Arg Arg Gly Glu Asn Pro Gly Thr Pro145 150
155 160Ala Leu Ser Ile Gly Phe Ser Val Ala Leu
Gly His Leu Leu Gly Ile 165 170
175His Tyr Thr Gly Cys Ser Met Asn Pro Ala Arg Ser Leu Ala Pro Ala
180 185 190Val Val Thr Gly Lys
Phe Asp Asp His Trp Val Phe Trp Ile Gly Pro 195
200 205Leu Val Gly Ala Ile Leu Gly Ser Leu Leu Tyr Asn
Tyr Val Leu Phe 210 215 220Pro Pro Ala
Lys Ser Leu Ser Glu Arg Leu Ala Val Leu Lys Gly Leu225
230 235 240Glu Pro Asp Thr Asp Trp Glu
Glu Arg Glu Val Arg Arg Arg Gln Ser 245
250 255Val Glu Leu His Ser Pro Gln Ser Leu Pro Arg Gly
Thr Lys Ala 260 265
27041323PRTHomo sapiens 41Met Ser Asp Arg Pro Thr Ala Arg Arg Trp Gly Lys
Cys Gly Pro Leu1 5 10
15Cys Thr Arg Glu Asn Ile Met Val Ala Phe Lys Gly Val Trp Thr Gln
20 25 30Ala Phe Trp Lys Ala Val Thr
Ala Glu Phe Leu Ala Met Leu Ile Phe 35 40
45Val Leu Leu Ser Leu Gly Ser Thr Ile Asn Trp Gly Gly Thr Glu
Lys 50 55 60Pro Leu Pro Val Asp Met
Val Leu Ile Ser Leu Cys Phe Gly Leu Ser65 70
75 80Ile Ala Thr Met Val Gln Cys Phe Gly His Ile
Ser Gly Gly His Ile 85 90
95Asn Pro Ala Val Thr Val Ala Met Val Cys Thr Arg Lys Ile Ser Ile
100 105 110Ala Lys Ser Val Phe Tyr
Ile Ala Ala Gln Cys Leu Gly Ala Ile Ile 115 120
125Gly Ala Gly Ile Leu Tyr Leu Val Thr Pro Pro Ser Val Val
Gly Gly 130 135 140Leu Gly Val Thr Met
Val His Gly Asn Leu Thr Ala Gly His Gly Leu145 150
155 160Leu Val Glu Leu Ile Ile Thr Phe Gln Leu
Val Phe Thr Ile Phe Ala 165 170
175Ser Cys Asp Ser Lys Arg Thr Asp Val Thr Gly Ser Ile Ala Leu Ala
180 185 190Ile Gly Phe Ser Val
Ala Ile Gly His Leu Phe Ala Ile Asn Tyr Thr 195
200 205Gly Ala Ser Met Asn Pro Ala Arg Ser Phe Gly Pro
Ala Val Ile Met 210 215 220Gly Asn Trp
Glu Asn His Trp Ile Tyr Trp Val Gly Pro Ile Ile Gly225
230 235 240Ala Val Leu Ala Gly Gly Leu
Tyr Glu Tyr Val Phe Cys Pro Asp Val 245
250 255Glu Phe Lys Arg Arg Phe Lys Glu Ala Phe Ser Lys
Ala Ala Gln Gln 260 265 270Thr
Lys Gly Ser Tyr Met Glu Val Glu Asp Asn Arg Ser Gln Val Glu 275
280 285Thr Asp Asp Leu Ile Leu Lys Pro Gly
Val Val His Val Ile Asp Val 290 295
300Asp Arg Gly Glu Glu Lys Lys Gly Lys Asp Gln Ser Gly Glu Val Leu305
310 315 320Ser Ser
Val42265PRTHomo sapiens 42Met Lys Lys Glu Val Cys Ser Val Ala Phe Leu Lys
Ala Val Phe Ala1 5 10
15Glu Phe Leu Ala Thr Leu Ile Phe Val Phe Phe Gly Leu Gly Ser Ala
20 25 30Leu Lys Trp Pro Ser Ala Leu
Pro Thr Ile Leu Gln Ile Ala Leu Ala 35 40
45Phe Gly Leu Ala Ile Gly Thr Leu Ala Gln Ala Leu Gly Pro Val
Ser 50 55 60Gly Gly His Ile Asn Pro
Ala Ile Thr Leu Ala Leu Leu Val Gly Asn65 70
75 80Gln Ile Ser Leu Leu Arg Ala Phe Phe Tyr Val
Ala Ala Gln Leu Val 85 90
95Gly Ala Ile Ala Gly Ala Gly Ile Leu Tyr Gly Val Ala Pro Leu Asn
100 105 110Ala Arg Gly Asn Leu Ala
Val Asn Ala Leu Asn Asn Asn Thr Thr Gln 115 120
125Gly Gln Ala Met Val Val Glu Leu Ile Leu Thr Phe Gln Leu
Ala Leu 130 135 140Cys Ile Phe Ala Ser
Thr Asp Ser Arg Arg Thr Ser Pro Val Gly Ser145 150
155 160Pro Ala Leu Ser Ile Gly Leu Ser Val Thr
Leu Gly His Leu Val Gly 165 170
175Ile Tyr Phe Thr Gly Cys Ser Met Asn Pro Ala Arg Ser Phe Gly Pro
180 185 190Ala Val Val Met Asn
Arg Phe Ser Pro Ala His Trp Val Phe Trp Val 195
200 205Gly Pro Ile Val Gly Ala Val Leu Ala Ala Ile Leu
Tyr Phe Tyr Leu 210 215 220Leu Phe Pro
Asn Ser Leu Ser Leu Ser Glu Arg Val Ala Ile Ile Lys225
230 235 240Gly Thr Tyr Glu Pro Asp Glu
Asp Trp Glu Glu Gln Arg Glu Glu Arg 245
250 255Lys Lys Thr Met Glu Leu Thr Thr Arg 260
26543282PRTHomo sapiens 43Met Asp Ala Glu Val Pro Gly Gly
Arg Gly Trp Ala Ser Met Leu Ala1 5 10
15Cys Arg Leu Trp Lys Ala Ile Ser Arg Ala Leu Phe Ala Glu
Phe Leu 20 25 30Ala Thr Gly
Leu Tyr Val Phe Phe Gly Val Gly Ser Val Met Arg Trp 35
40 45Pro Thr Ala Leu Pro Ser Val Leu Gln Ile Ala
Ile Thr Phe Asn Leu 50 55 60Val Thr
Ala Met Ala Val Gln Val Thr Trp Lys Thr Ser Gly Ala His65
70 75 80Ala Asn Pro Ala Val Thr Leu
Ala Phe Leu Val Gly Ser His Ile Ser 85 90
95Leu Pro Arg Ala Val Ala Tyr Val Ala Ala Gln Leu Val
Gly Ala Thr 100 105 110Val Gly
Ala Ala Leu Leu Tyr Gly Val Met Pro Gly Asp Ile Arg Glu 115
120 125Thr Leu Gly Ile Asn Val Val Arg Asn Ser
Val Ser Thr Gly Gln Ala 130 135 140Val
Ala Val Glu Leu Leu Leu Thr Leu Gln Leu Val Leu Cys Val Phe145
150 155 160Ala Ser Thr Asp Ser Arg
Gln Thr Ser Gly Ser Pro Ala Thr Met Ile 165
170 175Gly Ile Ser Trp Ala Leu Gly His Leu Ile Gly Ile
Leu Phe Thr Gly 180 185 190Cys
Ser Met Asn Pro Ala Arg Ser Phe Gly Pro Ala Ile Ile Ile Gly 195
200 205Lys Phe Thr Val His Trp Val Phe Trp
Val Gly Pro Leu Met Gly Ala 210 215
220Leu Leu Ala Ser Leu Ile Tyr Asn Phe Val Leu Phe Pro Asp Thr Lys225
230 235 240Thr Leu Ala Gln
Arg Leu Ala Ile Leu Thr Gly Thr Val Glu Val Gly 245
250 255Thr Gly Ala Arg Ala Gly Ala Glu Pro Leu
Lys Lys Glu Ser Gln Pro 260 265
270Gly Ser Gly Ala Val Glu Met Glu Ser Val 275
28044255PRTHomo sapiens 44Met Cys Glu Pro Glu Phe Gly Asn Asp Lys Ala Arg
Glu Pro Ser Val1 5 10
15Gly Gly Arg Trp Arg Val Ser Trp Tyr Glu Arg Phe Val Gln Pro Cys
20 25 30Leu Val Glu Leu Leu Gly Ser
Ala Leu Phe Ile Phe Ile Gly Cys Leu 35 40
45Ser Val Ile Glu Asn Gly Thr Asp Thr Gly Leu Leu Gln Pro Ala
Leu 50 55 60Ala His Gly Leu Ala Leu
Gly Leu Val Ile Ala Thr Leu Gly Asn Ile65 70
75 80Ser Gly Gly His Phe Asn Pro Ala Val Ser Leu
Ala Ala Met Leu Ile 85 90
95Gly Gly Leu Asn Leu Val Met Leu Leu Pro Tyr Trp Val Ser Gln Leu
100 105 110Leu Gly Gly Met Leu Gly
Ala Ala Leu Ala Lys Ala Val Ser Pro Glu 115 120
125Glu Arg Phe Trp Asn Ala Ser Gly Ala Ala Phe Val Thr Val
Gln Glu 130 135 140Gln Gly Gln Val Ala
Gly Ala Leu Val Ala Glu Ile Ile Leu Thr Thr145 150
155 160Leu Leu Ala Leu Ala Val Cys Met Gly Ala
Ile Asn Glu Lys Thr Lys 165 170
175Gly Pro Leu Ala Pro Phe Ser Ile Gly Phe Ala Val Thr Val Asp Ile
180 185 190Leu Ala Gly Gly Pro
Val Ser Gly Gly Cys Met Asn Pro Ala Arg Ala 195
200 205Phe Gly Pro Ala Val Val Ala Asn His Trp Asn Phe
His Trp Ile Tyr 210 215 220Trp Leu Gly
Pro Leu Leu Ala Gly Leu Leu Val Gly Leu Leu Ile Arg225
230 235 240Cys Phe Ile Gly Asp Gly Lys
Thr Arg Leu Ile Leu Lys Ala Arg 245 250
25545231PRTEscherichia coli 45Met Phe Arg Lys Leu Ala Ala
Glu Cys Phe Gly Thr Phe Trp Leu Val1 5 10
15Phe Gly Gly Cys Gly Ser Ala Val Leu Ala Ala Gly Phe
Pro Glu Leu 20 25 30Gly Ile
Gly Phe Ala Gly Val Ala Leu Ala Phe Gly Leu Thr Val Leu 35
40 45Thr Met Ala Phe Ala Val Gly His Ile Ser
Gly Gly His Phe Asn Pro 50 55 60Ala
Val Thr Ile Gly Leu Trp Ala Gly Gly Arg Phe Pro Ala Lys Glu65
70 75 80Val Val Gly Tyr Val Ile
Ala Gln Val Val Gly Gly Ile Val Ala Ala 85
90 95Ala Leu Leu Tyr Leu Ile Ala Ser Gly Lys Thr Gly
Phe Asp Ala Ala 100 105 110Ala
Ser Gly Phe Ala Ser Asn Gly Tyr Gly Glu His Ser Pro Gly Gly 115
120 125Tyr Ser Met Leu Ser Ala Leu Val Val
Glu Leu Val Leu Ser Ala Gly 130 135
140Phe Leu Leu Val Ile His Gly Ala Thr Asp Lys Phe Ala Pro Ala Gly145
150 155 160Phe Ala Pro Ile
Ala Ile Gly Leu Ala Leu Thr Leu Ile His Leu Ile 165
170 175Ser Ile Pro Val Thr Asn Thr Ser Val Asn
Pro Ala Arg Ser Thr Ala 180 185
190Val Ala Ile Phe Gln Gly Gly Trp Ala Leu Glu Gln Leu Trp Phe Phe
195 200 205Trp Val Val Pro Ile Val Gly
Gly Ile Ile Gly Gly Leu Ile Tyr Arg 210 215
220Thr Leu Leu Glu Lys Arg Asp225 23046271PRTHomo
sapiens 46Met Ser Pro Leu Leu Gly Leu Arg Ser Glu Leu Gln Asp Thr Cys
Thr1 5 10 15Ser Leu Gly
Leu Met Leu Ser Val Val Leu Leu Met Gly Leu Ala Arg 20
25 30Val Val Ala Arg Gln Gln Leu His Arg Pro
Val Ala His Ala Phe Val 35 40
45Leu Glu Phe Leu Ala Thr Phe Gln Leu Cys Cys Cys Thr His Glu Leu 50
55 60Gln Leu Leu Ser Glu Gln His Pro Ala
His Pro Thr Trp Thr Leu Thr65 70 75
80Leu Val Tyr Phe Phe Ser Leu Val His Gly Leu Thr Leu Val
Gly Thr 85 90 95Ser Ser
Asn Pro Cys Gly Val Met Met Gln Met Met Leu Gly Gly Met 100
105 110Ser Pro Glu Thr Gly Ala Val Arg Leu
Leu Ala Gln Leu Val Ser Ala 115 120
125Leu Cys Ser Arg Tyr Cys Thr Ser Ala Leu Trp Ser Leu Gly Leu Thr
130 135 140Gln Tyr His Val Ser Glu Arg
Ser Phe Ala Cys Lys Asn Pro Ile Arg145 150
155 160Val Asp Leu Leu Lys Ala Val Ile Thr Glu Ala Val
Cys Ser Phe Leu 165 170
175Phe His Ser Ala Leu Leu His Phe Gln Glu Val Arg Thr Lys Leu Arg
180 185 190Ile His Leu Leu Ala Ala
Leu Ile Thr Phe Leu Val Tyr Ala Gly Gly 195 200
205Ser Leu Thr Gly Ala Val Phe Asn Pro Ala Leu Ala Leu Ser
Leu His 210 215 220Phe Met Cys Phe Asp
Glu Ala Phe Pro Gln Phe Phe Ile Val Tyr Trp225 230
235 240Leu Ala Pro Ser Leu Gly Ile Leu Leu Met
Ile Leu Met Phe Ser Phe 245 250
255Phe Leu Pro Trp Leu His Asn Asn His Thr Ile Asn Lys Lys Glu
260 265 27047295PRTHomo sapiens
47Met Ala Gly Leu Asn Val Ser Leu Ser Phe Phe Phe Ala Thr Phe Ala1
5 10 15Leu Cys Glu Ala Ala Arg
Arg Ala Ser Lys Ala Leu Leu Pro Val Gly 20 25
30Ala Tyr Glu Val Phe Ala Arg Glu Ala Met Arg Thr Leu
Val Glu Leu 35 40 45Gly Pro Trp
Ala Gly Asp Phe Gly Pro Asp Leu Leu Leu Thr Leu Leu 50
55 60Phe Leu Leu Phe Leu Ala His Gly Val Thr Leu Asp
Gly Ala Ser Ala65 70 75
80Asn Pro Thr Val Ser Leu Gln Glu Phe Leu Met Ala Glu Gln Ser Leu
85 90 95Pro Gly Thr Leu Leu Lys
Leu Ala Ala Gln Gly Leu Gly Met Gln Ala 100
105 110Ala Cys Thr Leu Met Arg Leu Cys Trp Ala Trp Glu
Leu Ser Asp Leu 115 120 125His Leu
Leu Gln Ser Leu Met Ala Gln Ser Cys Ser Ser Ala Leu Arg 130
135 140Thr Ser Val Pro His Gly Ala Leu Val Glu Ala
Ala Cys Ala Phe Cys145 150 155
160Phe His Leu Thr Leu Leu His Leu Arg His Ser Pro Pro Ala Tyr Ser
165 170 175Gly Pro Ala Val
Ala Leu Leu Val Thr Val Thr Ala Tyr Thr Ala Gly 180
185 190Pro Phe Thr Ser Ala Phe Phe Asn Pro Ala Leu
Ala Ala Ser Val Thr 195 200 205Phe
Ala Cys Ser Gly His Thr Leu Leu Glu Tyr Val Gln Val Tyr Trp 210
215 220Leu Gly Pro Leu Thr Gly Met Val Leu Ala
Val Leu Leu His Gln Gly225 230 235
240Arg Leu Pro His Leu Phe Gln Arg Asn Leu Phe Tyr Gly Gln Lys
Asn 245 250 255Lys Tyr Arg
Ala Pro Arg Gly Lys Pro Ala Pro Ala Ser Gly Asp Thr 260
265 270Gln Thr Pro Ala Lys Gly Ser Ser Val Arg
Glu Pro Gly Arg Ser Gly 275 280
285Val Glu Gly Pro His Ser Ser 290
29548281PRTEscherichia coli 48Met Ser Gln Thr Ser Thr Leu Lys Gly Gln Cys
Ile Ala Glu Phe Leu1 5 10
15Gly Thr Gly Leu Leu Ile Phe Phe Gly Val Gly Cys Val Ala Ala Leu
20 25 30Lys Val Ala Gly Ala Ser Phe
Gly Gln Trp Glu Ile Ser Val Ile Trp 35 40
45Gly Leu Gly Val Ala Met Ala Ile Tyr Leu Thr Ala Gly Val Ser
Gly 50 55 60Ala His Leu Asn Pro Ala
Val Thr Ile Ala Leu Trp Leu Phe Ala Cys65 70
75 80Phe Asp Lys Arg Lys Val Ile Pro Phe Ile Val
Ser Gln Val Ala Gly 85 90
95Ala Phe Cys Ala Ala Ala Leu Val Tyr Gly Leu Tyr Tyr Asn Leu Phe
100 105 110Phe Asp Phe Glu Gln Thr
His His Ile Val Arg Gly Ser Ile Glu Ser 115 120
125Val Asp Leu Ala Gly Thr Phe Ser Thr Tyr Pro Asn Pro His
Ile Asn 130 135 140Phe Val Gln Ala Phe
Ala Val Glu Met Val Ile Thr Ala Ile Leu Ile145 150
155 160Gly Leu Ile Leu Ala Leu Thr Asp Asp Gly
Asn Gly Val Pro Arg Gly 165 170
175Pro Leu Ala Pro Leu Leu Ile Gly Leu Leu Ile Ala Val Ile Gly Ala
180 185 190Ser Met Gly Pro Leu
Thr Gly Phe Ala Met Asn Pro Ala Arg Asp Phe 195
200 205Gly Pro Lys Val Phe Ala Trp Leu Ala Gly Trp Gly
Asn Val Ala Phe 210 215 220Thr Gly Gly
Arg Asp Ile Pro Tyr Phe Leu Val Pro Leu Phe Ser Pro225
230 235 240Ile Val Gly Ala Ile Val Gly
Ala Phe Ala Tyr Arg Lys Leu Ile Gly 245
250 255Arg His Leu Pro Cys Asp Ile Cys Val Val Glu Glu
Lys Glu Thr Thr 260 265 270Thr
Pro Ser Glu Gln Lys Ala Ser Leu 275
28049292PRTHomo sapiens 49Met Gly Arg Gln Lys Glu Leu Val Ser Arg Cys Gly
Glu Met Leu His1 5 10
15Ile Arg Tyr Arg Leu Leu Arg Gln Ala Leu Ala Glu Cys Leu Gly Thr
20 25 30Leu Ile Leu Val Met Phe Gly
Cys Gly Ser Val Ala Gln Val Val Leu 35 40
45Ser Arg Gly Thr His Gly Gly Phe Leu Thr Ile Asn Leu Ala Phe
Gly 50 55 60Phe Ala Val Thr Leu Gly
Ile Leu Ile Ala Gly Gln Val Ser Gly Ala65 70
75 80His Leu Asn Pro Ala Val Thr Phe Ala Met Cys
Phe Leu Ala Arg Glu 85 90
95Pro Trp Ile Lys Leu Pro Ile Tyr Thr Leu Ala Gln Thr Leu Gly Ala
100 105 110Phe Leu Gly Ala Gly Ile
Val Phe Gly Leu Tyr Tyr Asp Ala Ile Trp 115 120
125His Phe Ala Asp Asn Gln Leu Phe Val Ser Gly Pro Asn Gly
Thr Ala 130 135 140Gly Ile Phe Ala Thr
Tyr Pro Ser Gly His Leu Asp Met Ile Asn Gly145 150
155 160Phe Phe Asp Gln Phe Ile Gly Thr Ala Ser
Leu Ile Val Cys Val Leu 165 170
175Ala Ile Val Asp Pro Tyr Asn Asn Pro Val Pro Arg Gly Leu Glu Ala
180 185 190Phe Thr Val Gly Leu
Val Val Leu Val Ile Gly Thr Ser Met Gly Phe 195
200 205Asn Ser Gly Tyr Ala Val Asn Pro Ala Arg Asp Phe
Gly Pro Arg Leu 210 215 220Phe Thr Ala
Leu Ala Gly Trp Gly Ser Ala Val Phe Thr Thr Gly Gln225
230 235 240His Trp Trp Trp Val Pro Ile
Val Ser Pro Leu Leu Gly Ser Ile Ala 245
250 255Gly Val Phe Val Tyr Gln Leu Met Ile Gly Cys His
Leu Glu Gln Pro 260 265 270Pro
Pro Ser Asn Glu Glu Glu Asn Val Lys Leu Ala His Val Lys His 275
280 285Lys Glu Gln Ile 29050342PRTHomo
sapiens 50Met Val Gln Ala Ser Gly His Arg Arg Ser Thr Arg Gly Ser Lys
Met1 5 10 15Val Ser Trp
Ser Val Ile Ala Lys Ile Gln Glu Ile Leu Gln Arg Lys 20
25 30Met Val Arg Glu Phe Leu Ala Glu Phe Met
Ser Thr Tyr Val Met Met 35 40
45Val Phe Gly Leu Gly Ser Val Ala His Met Val Leu Asn Lys Lys Tyr 50
55 60Gly Ser Tyr Leu Gly Val Asn Leu Gly
Phe Gly Phe Gly Val Thr Met65 70 75
80Gly Val His Val Ala Gly Arg Ile Ser Gly Ala His Met Asn
Ala Ala 85 90 95Val Thr
Phe Ala Asn Cys Ala Leu Gly Arg Val Pro Trp Arg Lys Phe 100
105 110Pro Val Tyr Val Leu Gly Gln Phe Leu
Gly Ser Phe Leu Ala Ala Ala 115 120
125Thr Ile Tyr Ser Leu Phe Tyr Thr Ala Ile Leu His Phe Ser Gly Gly
130 135 140Gln Leu Met Val Thr Gly Pro
Val Ala Thr Ala Gly Ile Phe Ala Thr145 150
155 160Tyr Leu Pro Asp His Met Thr Leu Trp Arg Gly Phe
Leu Asn Glu Ala 165 170
175Trp Leu Thr Gly Met Leu Gln Leu Cys Leu Phe Ala Ile Thr Asp Gln
180 185 190Glu Asn Asn Pro Ala Leu
Pro Gly Thr Glu Ala Leu Val Ile Gly Ile 195 200
205Leu Val Val Ile Ile Gly Val Ser Leu Gly Met Asn Thr Gly
Tyr Ala 210 215 220Ile Asn Pro Ser Arg
Asp Leu Pro Pro Arg Ile Phe Thr Phe Ile Ala225 230
235 240Gly Trp Gly Lys Gln Val Phe Ser Asn Gly
Glu Asn Trp Trp Trp Val 245 250
255Pro Val Val Ala Pro Leu Leu Gly Ala Tyr Leu Gly Gly Ile Ile Tyr
260 265 270Leu Val Phe Ile Gly
Ser Thr Ile Pro Arg Glu Pro Leu Lys Leu Glu 275
280 285Asp Ser Val Ala Tyr Glu Asp His Gly Ile Thr Val
Leu Pro Lys Met 290 295 300Gly Ser His
Glu Pro Thr Ile Ser Pro Leu Thr Pro Val Ser Val Ser305
310 315 320Pro Ala Asn Arg Ser Ser Val
His Pro Ala Pro Pro Leu His Glu Ser 325
330 335Met Ala Leu Glu His Phe 34051295PRTHomo
sapiens 51Met Gln Pro Glu Gly Ala Glu Lys Gly Lys Ser Phe Lys Gln Arg
Leu1 5 10 15Val Leu Lys
Ser Ser Leu Ala Lys Glu Thr Leu Ser Glu Phe Leu Gly 20
25 30Thr Phe Ile Leu Ile Val Leu Gly Cys Gly
Cys Val Ala Gln Ala Ile 35 40
45Leu Ser Arg Gly Arg Phe Gly Gly Val Ile Thr Ile Asn Val Gly Phe 50
55 60Ser Met Ala Val Ala Met Ala Ile Tyr
Val Ala Gly Gly Val Ser Gly65 70 75
80Gly His Ile Asn Pro Ala Val Ser Leu Ala Met Cys Leu Phe
Gly Arg 85 90 95Met Lys
Trp Phe Lys Leu Pro Phe Tyr Val Gly Ala Gln Phe Leu Gly 100
105 110Ala Phe Val Gly Ala Ala Thr Val Phe
Gly Ile Tyr Tyr Asp Gly Leu 115 120
125Met Ser Phe Ala Gly Gly Lys Leu Leu Ile Val Gly Glu Asn Ala Thr
130 135 140Ala His Ile Phe Ala Thr Tyr
Pro Ala Pro Tyr Leu Ser Leu Ala Asn145 150
155 160Ala Phe Ala Asp Gln Val Val Ala Thr Met Ile Leu
Leu Ile Ile Val 165 170
175Phe Ala Ile Phe Asp Ser Arg Asn Leu Gly Ala Pro Arg Gly Leu Glu
180 185 190Pro Ile Ala Ile Gly Leu
Leu Ile Ile Val Ile Ala Ser Ser Leu Gly 195 200
205Leu Asn Ser Gly Cys Ala Met Asn Pro Ala Arg Asp Leu Ser
Pro Arg 210 215 220Leu Phe Thr Ala Leu
Ala Gly Trp Gly Phe Glu Val Phe Arg Ala Gly225 230
235 240Asn Asn Phe Trp Trp Ile Pro Val Val Gly
Pro Leu Val Gly Ala Val 245 250
255Ile Gly Gly Leu Ile Tyr Val Leu Val Ile Glu Ile His His Pro Glu
260 265 270Pro Asp Ser Val Phe
Lys Ala Glu Gln Ser Glu Asp Lys Pro Glu Lys 275
280 285Tyr Glu Leu Ser Val Ile Met 290
29552301PRTHomo sapiens 52Met Val Phe Thr Gln Ala Pro Ala Glu Ile Met Gly
His Leu Arg Ile1 5 10
15Arg Ser Leu Leu Ala Arg Gln Cys Leu Ala Glu Phe Leu Gly Val Phe
20 25 30Val Leu Met Leu Leu Thr Gln
Gly Ala Val Ala Gln Ala Val Thr Ser 35 40
45Gly Glu Thr Lys Gly Asn Phe Phe Thr Met Phe Leu Ala Gly Ser
Leu 50 55 60Ala Val Thr Ile Ala Ile
Tyr Val Gly Gly Asn Val Ser Gly Ala His65 70
75 80Leu Asn Pro Ala Phe Ser Leu Ala Met Cys Ile
Val Gly Arg Leu Pro 85 90
95Trp Val Lys Leu Pro Ile Tyr Ile Leu Val Gln Leu Leu Ser Ala Phe
100 105 110Cys Ala Ser Gly Ala Thr
Tyr Val Leu Tyr His Asp Ala Leu Gln Asn 115 120
125Tyr Thr Gly Gly Asn Leu Thr Val Thr Gly Pro Lys Glu Thr
Ala Ser 130 135 140Ile Phe Ala Thr Tyr
Pro Ala Pro Tyr Leu Ser Leu Asn Asn Gly Phe145 150
155 160Leu Asp Gln Val Leu Gly Thr Gly Met Leu
Ile Val Gly Leu Leu Ala 165 170
175Ile Leu Asp Arg Arg Asn Lys Gly Val Pro Ala Gly Leu Glu Pro Val
180 185 190Val Val Gly Met Leu
Ile Leu Ala Leu Gly Leu Ser Met Gly Ala Asn 195
200 205Cys Gly Ile Pro Leu Asn Pro Ala Arg Asp Leu Gly
Pro Arg Leu Phe 210 215 220Thr Tyr Val
Ala Gly Trp Gly Pro Glu Val Phe Ser Ala Gly Asn Gly225
230 235 240Trp Trp Trp Val Pro Val Val
Ala Pro Leu Val Gly Ala Thr Val Gly 245
250 255Thr Ala Thr Tyr Gln Leu Leu Val Ala Leu His His
Pro Glu Gly Pro 260 265 270Glu
Pro Ala Gln Asp Leu Val Ser Ala Gln His Lys Ala Ser Glu Leu 275
280 285Glu Thr Pro Ala Ser Ala Gln Met Leu
Glu Cys Lys Leu 290 295
30053251PRTArabidopsis thaliana 53Met Pro Ile Arg Asn Ile Ala Ile Gly Arg
Pro Asp Glu Ala Thr Arg1 5 10
15Pro Asp Ala Leu Lys Ala Ala Leu Ala Glu Phe Ile Ser Thr Leu Ile
20 25 30Phe Val Val Ala Gly Ser
Gly Ser Gly Met Ala Phe Asn Lys Leu Thr 35 40
45Glu Asn Gly Ala Thr Thr Pro Ser Gly Leu Val Ala Ala Ala
Val Ala 50 55 60His Ala Phe Gly Leu
Phe Val Ala Val Ser Val Gly Ala Asn Ile Ser65 70
75 80Gly Gly His Val Asn Pro Ala Val Thr Phe
Gly Ala Phe Ile Gly Gly 85 90
95Asn Ile Thr Leu Leu Arg Gly Ile Leu Tyr Trp Ile Ala Gln Leu Leu
100 105 110Gly Ser Val Val Ala
Cys Leu Ile Leu Lys Phe Ala Thr Gly Gly Leu 115
120 125Ala Val Pro Ala Phe Gly Leu Ser Ala Gly Val Gly
Val Leu Asn Ala 130 135 140Phe Val Phe
Glu Ile Val Met Thr Phe Gly Leu Val Tyr Thr Val Tyr145
150 155 160Ala Thr Ala Ile Asp Pro Lys
Asn Gly Ser Leu Gly Thr Ile Ala Pro 165
170 175Ile Ala Ile Gly Phe Ile Val Gly Ala Asn Ile Leu
Ala Gly Gly Ala 180 185 190Phe
Ser Gly Ala Ser Met Asn Pro Ala Val Ala Phe Gly Pro Ala Val 195
200 205Val Ser Trp Thr Trp Thr Asn His Trp
Val Tyr Trp Ala Gly Pro Leu 210 215
220Val Gly Gly Gly Ile Ala Gly Leu Ile Tyr Glu Val Phe Phe Ile Asn225
230 235 240Thr Thr His Glu
Gln Leu Pro Thr Thr Asp Tyr 245
25054253PRTArabidopsis thaliana 54Met Pro Thr Arg Asn Ile Ala Ile Gly Gly
Val Gln Glu Glu Val Tyr1 5 10
15His Pro Asn Ala Leu Arg Ala Ala Leu Ala Glu Phe Ile Ser Thr Leu
20 25 30Ile Phe Val Phe Ala Gly
Ser Gly Ser Gly Ile Ala Phe Asn Lys Ile 35 40
45Thr Asp Asn Gly Ala Thr Thr Pro Ser Gly Leu Val Ala Ala
Ala Leu 50 55 60Ala His Ala Phe Gly
Leu Phe Val Ala Val Ser Val Gly Ala Asn Ile65 70
75 80Ser Gly Gly His Val Asn Pro Ala Val Thr
Phe Gly Val Leu Leu Gly 85 90
95Gly Asn Ile Thr Leu Leu Arg Gly Ile Leu Tyr Trp Ile Ala Gln Leu
100 105 110Leu Gly Ser Val Ala
Ala Cys Phe Leu Leu Ser Phe Ala Thr Gly Gly 115
120 125Glu Pro Ile Pro Ala Phe Gly Leu Ser Ala Gly Val
Gly Ser Leu Asn 130 135 140Ala Leu Val
Phe Glu Ile Val Met Thr Phe Gly Leu Val Tyr Thr Val145
150 155 160Tyr Ala Thr Ala Val Asp Pro
Lys Asn Gly Ser Leu Gly Thr Ile Ala 165
170 175Pro Ile Ala Ile Gly Phe Ile Val Gly Ala Asn Ile
Leu Ala Gly Gly 180 185 190Ala
Phe Ser Gly Ala Ser Met Asn Pro Ala Val Ala Phe Gly Pro Ala 195
200 205Val Val Ser Trp Thr Trp Thr Asn His
Trp Val Tyr Trp Ala Gly Pro 210 215
220Leu Ile Gly Gly Gly Leu Ala Gly Ile Ile Tyr Asp Phe Val Phe Ile225
230 235 240Asp Glu Asn Ala
His Glu Gln Leu Pro Thr Thr Asp Tyr 245
25055252PRTArabidopsis thaliana 55Met Pro Ile Asn Arg Ile Ala Ile Gly Thr
Pro Gly Glu Ala Ser Arg1 5 10
15Pro Asp Ala Ile Arg Ala Ala Phe Ala Glu Phe Phe Ser Met Val Ile
20 25 30Phe Val Phe Ala Gly Gln
Gly Ser Gly Met Ala Tyr Gly Lys Leu Thr 35 40
45Gly Asp Gly Pro Ala Thr Pro Ala Gly Leu Val Ala Ala Ser
Leu Ser 50 55 60His Ala Phe Ala Leu
Phe Val Ala Val Ser Val Gly Ala Asn Val Ser65 70
75 80Gly Gly His Val Asn Pro Ala Val Thr Phe
Gly Ala Phe Ile Gly Gly 85 90
95Asn Ile Thr Leu Leu Arg Ala Ile Leu Tyr Trp Ile Ala Gln Leu Leu
100 105 110Gly Ala Val Val Ala
Cys Leu Leu Leu Lys Val Ser Thr Gly Gly Met 115
120 125Glu Thr Ala Ala Phe Ser Leu Ser Tyr Gly Val Thr
Pro Trp Asn Ala 130 135 140Val Val Phe
Glu Ile Val Met Thr Phe Gly Leu Val Tyr Thr Val Tyr145
150 155 160Ala Thr Ala Val Asp Pro Lys
Lys Gly Asp Ile Gly Ile Ile Ala Pro 165
170 175Leu Ala Ile Gly Leu Ile Val Gly Ala Asn Ile Leu
Val Gly Gly Ala 180 185 190Phe
Asp Gly Ala Ser Met Asn Pro Ala Val Ser Phe Gly Pro Ala Val 195
200 205Val Ser Trp Ile Trp Thr Asn His Trp
Val Tyr Trp Val Gly Pro Phe 210 215
220Ile Gly Ala Ala Ile Ala Ala Ile Val Tyr Asp Thr Ile Phe Ile Gly225
230 235 240Ser Asn Gly His
Glu Pro Leu Pro Ser Asn Asp Phe 245
25056250PRTZea mays 56Met Pro Ile Asn Arg Ile Ala Leu Gly Ser His Gln Glu
Val Tyr His1 5 10 15Pro
Gly Ala Leu Lys Ala Ala Phe Ala Glu Phe Ile Ser Thr Leu Ile 20
25 30Phe Val Phe Ala Gly Gln Gly Ser
Gly Met Ala Phe Ser Lys Leu Thr 35 40
45Gly Gly Gly Pro Thr Thr Pro Ala Gly Leu Ile Ala Ala Ala Val Ala
50 55 60His Ala Phe Ala Leu Phe Val Ala
Val Ser Val Gly Ala Asn Ile Ser65 70 75
80Gly Gly His Val Asn Pro Ala Val Thr Phe Gly Ala Phe
Val Gly Gly 85 90 95Asn
Ile Thr Leu Phe Arg Gly Leu Leu Tyr Trp Val Ala Gln Leu Leu
100 105 110Gly Ser Thr Val Ala Cys Phe
Leu Leu Arg Phe Ser Thr Gly Gly Gln 115 120
125Ala Thr Gly Thr Phe Gly Leu Thr Gly Val Ser Val Trp Glu Ala
Leu 130 135 140Val Leu Glu Ile Val Met
Thr Phe Gly Leu Val Tyr Thr Val Tyr Ala145 150
155 160Thr Ala Val Asp Pro Lys Lys Gly Ser Leu Gly
Thr Ile Ala Pro Ile 165 170
175Ala Ile Gly Phe Ile Val Gly Ala Asn Ile Leu Val Gly Gly Ala Phe
180 185 190Asp Gly Ala Ser Met Asn
Pro Ala Val Ser Phe Gly Pro Ala Leu Val 195 200
205Ser Trp Glu Trp Gly Tyr Gln Trp Val Tyr Trp Val Gly Pro
Leu Ile 210 215 220Gly Gly Gly Leu Ala
Gly Val Ile Tyr Glu Leu Leu Phe Ile Ser His225 230
235 240Thr His Glu Gln Leu Pro Ser Thr Asp Tyr
245 25057254PRTZea mays 57Met Pro Val Ser
Arg Ile Ala Val Gly Ala Pro Gly Glu Leu Ser His1 5
10 15Pro Asp Thr Ala Lys Ala Ala Val Ala Glu
Phe Ile Ser Thr Leu Ile 20 25
30Phe Val Phe Ala Gly Ser Gly Ser Gly Met Ala Phe Ser Lys Leu Thr
35 40 45Asp Gly Gly Ala Ala Thr Pro Ala
Gly Leu Ile Ala Ala Ser Leu Ala 50 55
60His Ala Leu Ala Leu Phe Val Ala Val Ser Val Gly Ala Asn Ile Ser65
70 75 80Gly Gly His Val Asn
Pro Ala Val Thr Phe Gly Ala Phe Val Gly Gly 85
90 95Asn Ile Ser Leu Leu Lys Ala Leu Val Tyr Trp
Val Ala Gln Leu Leu 100 105
110Gly Ser Val Val Ala Cys Leu Leu Leu Lys Ile Ala Thr Gly Gly Ala
115 120 125Ala Leu Gly Ala Phe Ser Leu
Ser Ala Gly Val Gly Ala Met Asn Ala 130 135
140Val Val Leu Glu Met Val Met Thr Phe Gly Leu Val Tyr Thr Val
Tyr145 150 155 160Ala Thr
Ala Val Asp Pro Lys Lys Gly Asp Leu Gly Val Ile Ala Pro
165 170 175Ile Ala Ile Gly Phe Ile Val
Gly Ala Asn Ile Leu Ala Gly Gly Ala 180 185
190Phe Asp Gly Ala Ser Met Asn Pro Ala Val Ser Phe Gly Pro
Ala Val 195 200 205Val Thr Gly Val
Trp Glu Asn His Trp Val Tyr Trp Val Gly Pro Leu 210
215 220Ala Gly Ala Ala Ile Ala Ala Leu Val Tyr Asp Ile
Ile Phe Ile Gly225 230 235
240Gln Arg Pro His Gln Gln Leu Pro Thr Thr Ala Ala Asp Tyr
245 25058250PRTArabidopsis thaliana 58Met Ala Gly Val
Ala Phe Gly Ser Phe Asp Asp Ser Phe Ser Leu Ala1 5
10 15Ser Leu Arg Ala Tyr Leu Ala Glu Phe Ile
Ser Thr Leu Leu Phe Val 20 25
30Phe Ala Gly Val Gly Ser Ala Ile Ala Tyr Ala Lys Leu Thr Ser Asp
35 40 45Ala Ala Leu Asp Thr Pro Gly Leu
Val Ala Ile Ala Val Cys His Gly 50 55
60Phe Ala Leu Phe Val Ala Val Ala Ile Gly Ala Asn Ile Ser Gly Gly65
70 75 80His Val Asn Pro Ala
Val Thr Phe Gly Leu Ala Val Gly Gly Gln Ile 85
90 95Thr Val Ile Thr Gly Val Phe Tyr Trp Ile Ala
Gln Leu Leu Gly Ser 100 105
110Thr Ala Ala Cys Phe Leu Leu Lys Tyr Val Thr Gly Gly Leu Ala Val
115 120 125Pro Thr His Ser Val Ala Ala
Gly Leu Gly Ser Ile Glu Gly Val Val 130 135
140Met Glu Ile Ile Ile Thr Phe Ala Leu Val Tyr Thr Val Tyr Ala
Thr145 150 155 160Ala Ala
Asp Pro Lys Lys Gly Ser Leu Gly Thr Ile Ala Pro Leu Ala
165 170 175Ile Gly Leu Ile Val Gly Ala
Asn Ile Leu Ala Ala Gly Pro Phe Ser 180 185
190Gly Gly Ser Met Asn Pro Ala Arg Ser Phe Gly Pro Ala Val
Ala Ala 195 200 205Gly Asp Phe Ser
Gly His Trp Val Tyr Trp Val Gly Pro Leu Ile Gly 210
215 220Gly Gly Leu Ala Gly Leu Ile Tyr Gly Asn Val Phe
Met Gly Ser Ser225 230 235
240Glu His Val Pro Leu Ala Ser Ala Asp Phe 245
25059250PRTArabidopsis thaliana 59Met Val Lys Ile Glu Ile Gly Ser
Val Gly Asp Ser Phe Ser Val Ala1 5 10
15Ser Leu Lys Ala Tyr Leu Ser Glu Phe Ile Ala Thr Leu Leu
Phe Val 20 25 30Phe Ala Gly
Val Gly Ser Ala Leu Ala Phe Ala Lys Leu Thr Ser Asp 35
40 45Ala Ala Leu Asp Pro Ala Gly Leu Val Ala Val
Ala Val Ala His Ala 50 55 60Phe Ala
Leu Phe Val Gly Val Ser Ile Ala Ala Asn Ile Ser Gly Gly65
70 75 80His Leu Asn Pro Ala Val Thr
Leu Gly Leu Ala Val Gly Gly Asn Ile 85 90
95Thr Val Ile Thr Gly Phe Phe Tyr Trp Ile Ala Gln Cys
Leu Gly Ser 100 105 110Ile Val
Ala Cys Leu Leu Leu Val Phe Val Thr Asn Gly Glu Ser Val 115
120 125Pro Thr His Gly Val Ala Ala Gly Leu Gly
Ala Ile Glu Gly Val Val 130 135 140Met
Glu Ile Val Val Thr Phe Ala Leu Val Tyr Thr Val Tyr Ala Thr145
150 155 160Ala Ala Asp Pro Lys Lys
Gly Ser Leu Gly Thr Ile Ala Pro Ile Ala 165
170 175Ile Gly Phe Ile Val Gly Ala Asn Ile Leu Ala Ala
Gly Pro Phe Ser 180 185 190Gly
Gly Ser Met Asn Pro Ala Arg Ser Phe Gly Pro Ala Val Val Ser 195
200 205Gly Asp Phe Ser Gln Ile Trp Ile Tyr
Trp Val Gly Pro Leu Val Gly 210 215
220Gly Ala Leu Ala Gly Leu Ile Tyr Gly Asp Val Phe Ile Gly Ser Tyr225
230 235 240Ala Pro Ala Pro
Thr Thr Glu Ser Tyr Pro 245
25060250PRTArabidopsis thaliana 60Met Val Lys Ile Glu Val Gly Ser Val Gly
Asp Ser Phe Ser Val Ser1 5 10
15Ser Leu Lys Ala Tyr Leu Ser Glu Phe Ile Ala Thr Leu Leu Phe Val
20 25 30Phe Ala Gly Val Gly Ser
Ala Val Ala Phe Ala Lys Leu Thr Ser Asp 35 40
45Gly Ala Leu Asp Pro Ala Gly Leu Val Ala Ile Ala Ile Ala
His Ala 50 55 60Phe Ala Leu Phe Val
Gly Val Ser Ile Ala Ala Asn Ile Ser Gly Gly65 70
75 80His Leu Asn Pro Ala Val Thr Leu Gly Leu
Ala Ile Gly Gly Asn Ile 85 90
95Thr Leu Ile Thr Gly Phe Phe Tyr Trp Ile Ala Gln Cys Leu Gly Ser
100 105 110Ile Val Ala Cys Leu
Leu Leu Val Phe Val Thr Asn Gly Lys Ser Val 115
120 125Pro Thr His Gly Val Ser Ala Gly Leu Gly Ala Val
Glu Gly Val Val 130 135 140Met Glu Ile
Val Val Thr Phe Ala Leu Val Tyr Thr Val Tyr Ala Thr145
150 155 160Ala Ala Asp Pro Lys Lys Gly
Ser Leu Gly Thr Ile Ala Pro Ile Ala 165
170 175Ile Gly Phe Ile Val Gly Ala Asn Ile Leu Ala Ala
Gly Pro Phe Ser 180 185 190Gly
Gly Ser Met Asn Pro Ala Arg Ser Phe Gly Pro Ala Val Val Ser 195
200 205Gly Asp Leu Ser Gln Ile Trp Ile Tyr
Trp Val Gly Pro Leu Val Gly 210 215
220Gly Ala Leu Ala Gly Leu Ile Tyr Gly Asp Val Phe Ile Gly Ser Tyr225
230 235 240Glu Ala Val Glu
Thr Arg Glu Ile Arg Val 245 25061249PRTZea
mays 61Met Val Lys Leu Ala Phe Gly Ser Val Gly Asp Ser Phe Ser Ala Thr1
5 10 15Ser Ile Lys Ala Tyr
Val Ala Glu Phe Ile Ala Thr Leu Leu Phe Val 20
25 30Phe Ala Gly Val Gly Ser Ala Ile Ala Tyr Gly Gln
Leu Thr Asn Gly 35 40 45Gly Ala
Leu Asp Pro Ala Gly Leu Val Ala Ile Ala Ile Ala His Ala 50
55 60Leu Ala Leu Phe Val Gly Val Ser Val Ala Ala
Asn Ile Ser Gly Gly65 70 75
80His Leu Asn Pro Ala Val Thr Phe Gly Leu Ala Val Gly Gly His Ile
85 90 95Thr Ile Leu Thr Gly
Val Phe Tyr Trp Val Ala Gln Leu Leu Gly Ala 100
105 110Thr Val Ala Cys Leu Leu Leu Gly Phe Val Thr His
Gly Lys Ala Ile 115 120 125Pro Thr
His Ala Val Ala Gly Ile Ser Glu Leu Glu Gly Val Val Phe 130
135 140Glu Val Val Ile Thr Phe Ala Leu Val Tyr Thr
Val Tyr Ala Thr Ala145 150 155
160Ala Asp Pro Lys Lys Gly Ser Leu Gly Thr Ile Ala Pro Ile Ala Ile
165 170 175Gly Phe Ile Val
Gly Ala Asn Ile Leu Ala Ala Gly Pro Phe Ser Gly 180
185 190Gly Ser Met Asn Pro Ala Arg Ser Phe Gly Pro
Ala Val Ala Ala Gly 195 200 205Asp
Phe Ala Gly Asn Trp Val Tyr Trp Val Gly Pro Leu Val Gly Gly 210
215 220Gly Leu Ala Gly Leu Val Tyr Gly Asp Val
Phe Ile Gly Gly Ser Tyr225 230 235
240Gln Gln Val Ala Asp Gln Asp Tyr Ala
24562250PRTZea mays 62Met Val Lys Leu Ala Phe Gly Ser Val Gly Asp Ser Phe
Ser Val Thr1 5 10 15Ser
Ile Lys Ala Tyr Val Ala Glu Phe Ile Ala Thr Leu Leu Phe Val 20
25 30Phe Ala Gly Val Gly Ser Ala Ile
Ala Phe Gly Gln Leu Thr Asn Gly 35 40
45Gly Ala Leu Asp Pro Ala Gly Leu Val Ala Ile Ala Val Ala His Ala
50 55 60Leu Ala Leu Phe Val Gly Val Ser
Val Ala Ala Asn Thr Ser Gly Gly65 70 75
80His Leu Asn Pro Ala Val Thr Phe Gly Leu Ala Val Gly
Gly His Ile 85 90 95Thr
Val Leu Thr Gly Leu Phe Tyr Trp Val Ala Gln Leu Leu Gly Ala
100 105 110Ser Val Ala Cys Leu Leu Leu
Arg Phe Val Thr His Gly Lys Ala Ile 115 120
125Pro Thr His Gly Val Ser Gly Gly Thr Thr Glu Leu Glu Gly Val
Val 130 135 140Phe Glu Ile Val Ile Thr
Phe Ala Leu Val Tyr Thr Val Tyr Ala Thr145 150
155 160Ala Ala Asp Pro Lys Lys Gly Ser Leu Gly Thr
Ile Ala Pro Ile Ala 165 170
175Ile Gly Phe Ile Val Gly Ala Asn Ile Leu Ala Ala Gly Pro Phe Ser
180 185 190Gly Gly Ser Met Asn Pro
Ala Arg Ser Phe Gly Pro Ala Val Ala Ala 195 200
205Ala Asp Phe Ala Gly Asn Trp Val Tyr Trp Val Gly Pro Leu
Ile Gly 210 215 220Gly Gly Leu Ala Gly
Leu Val Tyr Gly Asp Val Phe Ile Gly Gly Ser225 230
235 240Tyr Gln Gln Val Ala Asp Gln Asp Tyr Ala
245 25063248PRTZea mays 63Met Val Lys Leu
Ala Phe Gly Ser Phe Arg Asp Ser Leu Ser Ala Ala1 5
10 15Ser Leu Lys Ala Tyr Val Ala Glu Phe Ile
Ala Thr Leu Leu Phe Val 20 25
30Phe Ala Gly Val Gly Ser Ala Ile Ala Tyr Ser Gln Leu Thr Lys Gly
35 40 45Gly Ala Leu Asp Pro Ala Gly Leu
Val Ala Ile Ala Ile Ala His Ala 50 55
60Phe Ala Leu Phe Val Gly Val Ser Met Ala Ala Asn Ile Ser Gly Gly65
70 75 80His Leu Asn Pro Ala
Val Thr Phe Gly Leu Ala Val Gly Gly His Ile 85
90 95Thr Ile Leu Thr Gly Ile Leu Tyr Trp Val Ala
Gln Leu Leu Gly Ala 100 105
110Ser Val Ala Cys Phe Leu Leu Gln Tyr Val Thr His Gly Gln Ala Ile
115 120 125Pro Thr His Gly Val Ser Gly
Ile Ser Glu Ile Glu Gly Val Val Met 130 135
140Glu Ile Val Ile Thr Phe Ala Leu Val Tyr Thr Val Tyr Ala Thr
Ala145 150 155 160Ala Asp
Pro Lys Lys Gly Ser Leu Gly Thr Ile Ala Pro Met Ala Ile
165 170 175Gly Phe Ile Val Gly Ala Asn
Ile Leu Ala Ala Gly Pro Phe Ser Gly 180 185
190Gly Ser Met Asn Pro Ala Arg Ser Phe Gly Pro Ala Val Ala
Ala Gly 195 200 205Asn Phe Ala Gly
Asn Trp Val Tyr Trp Val Gly Pro Leu Val Gly Gly 210
215 220Gly Leu Ala Gly Leu Val Tyr Gly Asp Val Phe Ile
Ala Ser Tyr Gln225 230 235
240Pro Val Gly Gln Gln Glu Tyr Pro 24564268PRTArabidopsis
thaliana 64Met Ala Thr Ser Ala Arg Arg Ala Tyr Gly Phe Gly Arg Ala Asp
Glu1 5 10 15Ala Thr His
Pro Asp Ser Ile Arg Ala Thr Leu Ala Glu Phe Leu Ser 20
25 30Thr Phe Val Phe Val Phe Ala Ala Glu Gly
Ser Ile Leu Ser Leu Asp 35 40
45Lys Leu Tyr Trp Glu His Ala Ala His Ala Gly Thr Asn Thr Pro Gly 50
55 60Gly Leu Ile Leu Val Ala Leu Ala His
Ala Phe Ala Leu Phe Ala Ala65 70 75
80Val Ser Ala Ala Ile Asn Val Ser Gly Gly His Val Asn Pro
Ala Val 85 90 95Thr Phe
Gly Ala Leu Val Gly Gly Arg Val Thr Ala Ile Arg Ala Ile 100
105 110Tyr Tyr Trp Ile Ala Gln Leu Leu Gly
Ala Ile Leu Ala Cys Leu Leu 115 120
125Leu Arg Leu Thr Thr Asn Gly Met Arg Pro Val Gly Phe Arg Leu Ala
130 135 140Ser Gly Val Gly Ala Val Asn
Gly Leu Val Leu Glu Ile Ile Leu Thr145 150
155 160Phe Gly Leu Val Tyr Val Val Tyr Ser Thr Leu Ile
Asp Pro Lys Arg 165 170
175Gly Ser Leu Gly Ile Ile Ala Pro Leu Ala Ile Gly Leu Ile Val Gly
180 185 190Ala Asn Ile Leu Val Gly
Gly Pro Phe Ser Gly Ala Ser Met Asn Pro 195 200
205Ala Arg Ala Phe Gly Pro Ala Leu Val Gly Trp Arg Trp His
Asp His 210 215 220Trp Ile Tyr Trp Val
Gly Pro Phe Ile Gly Ser Ala Leu Ala Ala Leu225 230
235 240Ile Tyr Glu Tyr Met Val Ile Pro Thr Glu
Pro Pro Thr His His Ala 245 250
255His Gly Val His Gln Pro Leu Ala Pro Glu Asp Tyr 260
26565267PRTArabidopsis thaliana 65Met Ala Thr Ser Ala Arg
Arg Ala Tyr Gly Phe Gly Arg Ala Asp Glu1 5
10 15Ala Thr His Pro Asp Ser Ile Arg Ala Thr Leu Ala
Glu Phe Leu Ser 20 25 30Thr
Phe Val Phe Val Phe Ala Gly Glu Gly Ser Ile Leu Ala Leu Asp 35
40 45Lys Leu Tyr Trp Asp Thr Ala Ala His
Thr Gly Thr Asn Thr Pro Gly 50 55
60Gly Leu Val Leu Val Ala Leu Ala His Ala Leu Ala Leu Phe Ala Ala65
70 75 80Val Ser Ala Ala Ile
Asn Val Ser Gly Gly His Val Asn Pro Ala Val 85
90 95Thr Phe Ala Ala Leu Ile Gly Gly Arg Ile Ser
Val Ile Arg Ala Ile 100 105
110Tyr Tyr Trp Val Ala Gln Leu Ile Gly Ala Ile Leu Ala Cys Leu Leu
115 120 125Leu Arg Leu Ala Thr Asn Gly
Leu Arg Pro Val Gly Phe His Val Ala 130 135
140Ser Gly Val Ser Glu Leu His Gly Leu Leu Met Glu Ile Ile Leu
Thr145 150 155 160Phe Ala
Leu Val Tyr Val Val Tyr Ser Thr Ala Ile Asp Pro Lys Arg
165 170 175Gly Ser Ile Gly Ile Ile Ala
Pro Leu Ala Ile Gly Leu Ile Val Gly 180 185
190Ala Asn Ile Leu Val Gly Gly Pro Phe Asp Gly Ala Ser Met
Asn Pro 195 200 205Ala Arg Ala Phe
Gly Pro Ala Leu Val Gly Trp Arg Trp Ser Asn His 210
215 220Trp Ile Tyr Trp Val Gly Pro Phe Ile Gly Gly Ala
Leu Ala Ala Leu225 230 235
240Ile Tyr Glu Tyr Met Ile Ile Pro Ser Val Asn Glu Pro Pro His His
245 250 255Ser Thr His Gln Pro
Leu Ala Pro Glu Asp Tyr 260 26566262PRTZea
mays 66Met Ser Thr Gly Val Arg Pro Gly Arg Arg Phe Thr Val Gly Arg Ser1
5 10 15Glu Asp Ala Thr His
Pro Asp Thr Ile Arg Ala Ala Ile Ser Glu Phe 20
25 30Ile Ala Thr Ala Ile Phe Val Phe Ala Ala Glu Gly
Ser Val Leu Ser 35 40 45Leu Gly
Lys Met Tyr His Asp Met Ser Thr Ala Gly Gly Leu Val Ala 50
55 60Val Ala Leu Ala His Ala Leu Ala Leu Ala Val
Ala Val Ala Val Ala65 70 75
80Val Asn Ile Ser Gly Gly His Val Asn Pro Ala Val Thr Phe Gly Ala
85 90 95Leu Val Gly Gly Arg
Val Ser Leu Val Arg Ala Val Leu Tyr Trp Val 100
105 110Ala Gln Leu Leu Gly Ala Val Ala Ala Thr Leu Leu
Leu Arg Leu Ala 115 120 125Thr Gly
Gly Met Arg Pro Pro Gly Phe Ala Leu Ala Ser Gly Val Gly 130
135 140Asp Trp His Ala Val Leu Leu Glu Ala Val Met
Thr Phe Gly Leu Met145 150 155
160Tyr Ala Tyr Tyr Ala Thr Val Ile Asp Pro Lys Arg Gly His Val Gly
165 170 175Thr Ile Ala Pro
Leu Ala Val Gly Phe Leu Leu Gly Ala Asn Val Leu 180
185 190Ala Gly Gly Pro Phe Asp Gly Ala Gly Met Asn
Pro Ala Arg Val Phe 195 200 205Gly
Pro Ala Leu Val Gly Trp Arg Trp Arg His His Trp Val Tyr Trp 210
215 220Leu Gly Pro Phe Leu Gly Ala Gly Leu Ala
Gly Leu Val Tyr Glu Tyr225 230 235
240Leu Val Ile Pro Ser Ala Asp Ala Ala Val Pro His Ala His Gln
Pro 245 250 255Leu Ala Pro
Glu Asp Tyr 26067266PRTZea mays 67Met Ser Thr Ala Thr Gly Val
Arg Ala Gly Arg Arg Phe Thr Val Gly1 5 10
15Arg Ser Glu Asp Ala Thr His Pro Asp Thr Ile Arg Ala
Ala Ile Ser 20 25 30Glu Phe
Ile Ala Thr Ala Ile Phe Val Phe Ala Ala Glu Gly Ser Val 35
40 45Leu Ser Leu Gly Lys Met Tyr His Asp His
Ser Thr Ile Ser Thr Ala 50 55 60Gly
Gly Leu Val Ala Val Ala Leu Ala His Ala Leu Gly Leu Ala Val65
70 75 80Ala Val Ala Val Ala Val
Asn Val Ser Gly Gly His Val Asn Pro Ala 85
90 95Val Thr Phe Gly Ala Leu Val Gly Gly Arg Val Ser
Leu Val Arg Ala 100 105 110Val
Leu Tyr Trp Ala Ala Gln Leu Leu Gly Ala Val Ala Ala Thr Leu 115
120 125Leu Leu Arg Leu Ala Thr Gly Gly Ala
Arg Pro Pro Gly Phe Ala Leu 130 135
140Ala Ser Gly Val Gly Asp Gly His Ala Val Leu Leu Glu Ala Val Met145
150 155 160Thr Phe Gly Phe
Val Tyr Ala Tyr Tyr Ala Thr Val Val Asp Pro Lys 165
170 175Arg Gly His Leu Gly Thr Ile Ala Pro Leu
Ala Val Gly Phe Leu Leu 180 185
190Gly Ala Asn Val Leu Ala Gly Gly Pro Phe Asp Gly Ala Gly Met Asn
195 200 205Pro Ala Arg Val Phe Gly Pro
Ala Leu Val Gly Trp Arg Trp Arg His 210 215
220His Trp Val Tyr Trp Leu Gly Pro Phe Leu Gly Ala Gly Leu Ala
Gly225 230 235 240Leu Val
Tyr Glu Tyr Leu Leu Ile Pro Pro Ala Asp Ala Val Pro His
245 250 255Thr His Gln Pro Leu Ala Pro
Glu Asp Tyr 260 26568249PRTArabidopsis
thaliana 68Met Lys Lys Ile Glu Leu Gly His His Ser Glu Ala Ala Lys Pro
Asp1 5 10 15Cys Ile Lys
Ala Leu Ile Val Glu Phe Ile Thr Thr Phe Leu Phe Val 20
25 30Phe Ala Gly Val Gly Ser Ala Met Ala Thr
Asp Ser Leu Val Gly Asn 35 40
45Thr Leu Val Gly Leu Phe Ala Val Ala Val Ala His Ala Phe Val Val 50
55 60Ala Val Met Ile Ser Ala Gly His Ile
Ser Gly Gly His Leu Asn Pro65 70 75
80Ala Val Thr Leu Gly Leu Leu Leu Gly Gly His Ile Ser Val
Phe Arg 85 90 95Ala Phe
Leu Tyr Trp Ile Asp Gln Leu Leu Ala Ser Ser Ala Ala Cys 100
105 110Phe Leu Leu Ser Tyr Leu Thr Gly Gly
Met Gly Thr Pro Val His Thr 115 120
125Leu Ala Ser Gly Val Ser Tyr Thr Gln Gly Ile Ile Trp Glu Ile Ile
130 135 140Leu Thr Phe Ser Leu Leu Phe
Thr Val Tyr Ala Thr Ile Val Asp Pro145 150
155 160Lys Lys Gly Ser Leu Asp Gly Phe Gly Pro Leu Leu
Thr Gly Phe Val 165 170
175Val Gly Ala Asn Ile Leu Ala Gly Gly Ala Phe Ser Gly Ala Ser Met
180 185 190Asn Pro Ala Arg Ser Phe
Gly Pro Ala Leu Val Ser Gly Asn Trp Thr 195 200
205Asp His Trp Val Tyr Trp Val Gly Pro Leu Ile Gly Gly Gly
Leu Ala 210 215 220Gly Phe Ile Tyr Glu
Asn Val Leu Ile Asp Arg Pro His Val Pro Val225 230
235 240Ala Asp Asp Glu Gln Pro Leu Leu Asn
24569255PRTZea mays 69Met Ala Lys Leu Met Asn Lys Leu Val Asp
Ser Phe Glu His Asp Glu1 5 10
15Ile Pro Asp Val Gly Cys Val Arg Ala Val Leu Ala Glu Leu Val Leu
20 25 30Thr Phe Leu Phe Val Phe
Thr Gly Val Ser Ala Ala Met Ala Ala Gly 35 40
45Ser Asp Gly Lys Pro Gly Asp Ala Met Pro Met Ala Thr Leu
Ala Ala 50 55 60Val Ala Ile Ala His
Ala Leu Ala Ala Gly Val Leu Val Thr Ala Gly65 70
75 80Phe His Val Ser Gly Gly His Leu Asn Pro
Ala Val Thr Val Gly Leu 85 90
95Met Val Arg Gly His Ile Thr Lys Leu Arg Ala Val Leu Tyr Val Ala
100 105 110Ala Gln Leu Leu Ala
Ser Ser Ala Ala Cys Val Leu Leu Arg Phe Leu 115
120 125Ser Gly Gly Met Val Thr Pro Val His Ala Leu Gly
Arg Gly Ile Ser 130 135 140Pro Met Gln
Gly Leu Val Met Glu Val Ile Leu Thr Phe Ser Leu Leu145
150 155 160Phe Val Thr Tyr Ala Met Ile
Leu Asp Pro Arg Ser Gln Val Arg Ala 165
170 175Ile Gly Pro Leu Leu Thr Gly Leu Ile Val Gly Ala
Asn Ser Leu Ala 180 185 190Gly
Gly Asn Phe Thr Gly Ala Ser Met Asn Pro Ala Arg Ser Phe Gly 195
200 205Pro Ala Leu Ala Thr Gly Asp Trp Thr
Asn His Trp Val Tyr Trp Ile 210 215
220Gly Pro Leu Leu Gly Gly Pro Leu Ala Gly Phe Val Tyr Glu Ser Leu225
230 235 240Phe Leu Val Gln
Lys Met His Glu Pro Leu Leu Asn Gly Glu Val 245
250 25570257PRTZea mays 70Met Ala Lys Leu Val Asn
Lys Leu Val Asp Ser Phe Asp His Asp Glu1 5
10 15Ala Pro Ala Pro Asp Val Gly Cys Val Arg Ala Val
Leu Ala Glu Leu 20 25 30Val
Leu Thr Phe Leu Phe Val Phe Thr Gly Val Ser Ala Ser Met Ala 35
40 45Ala Gly Ala Gly Gly Lys Pro Gly Glu
Ala Met Pro Met Ala Thr Leu 50 55
60Ala Ala Val Ala Ile Ala His Ala Leu Ala Ala Gly Val Leu Val Thr65
70 75 80Ala Gly Phe His Val
Ser Gly Gly His Leu Asn Pro Ala Val Thr Val 85
90 95Gly Ile Leu Val Arg Gly His Ile Thr Lys Leu
Arg Ala Leu Leu Tyr 100 105
110Val Ala Ala Gln Leu Leu Ala Ser Ser Leu Ala Cys Ile Leu Leu Arg
115 120 125Tyr Leu Ser Gly Gly Met Val
Thr Pro Val His Ala Leu Gly Ala Gly 130 135
140Ile Arg Pro Met Gln Gly Leu Val Met Glu Val Ile Leu Thr Phe
Ser145 150 155 160Leu Leu
Phe Val Thr Tyr Ala Met Ile Leu Asp Pro Arg Ser Gln Val
165 170 175Arg Thr Ile Gly Pro Leu Leu
Thr Gly Leu Ile Val Gly Ala Asn Ser 180 185
190Leu Ala Gly Gly Asn Phe Thr Gly Ala Ser Met Asn Pro Ala
Arg Ser 195 200 205Phe Gly Pro Ala
Met Ala Thr Gly Val Trp Thr Asn His Trp Val Tyr 210
215 220Trp Ile Gly Pro Leu Leu Gly Gly Ser Leu Ala Gly
Phe Val Tyr Glu225 230 235
240Ser Leu Phe Met Val Asn Lys Thr His Glu Pro Leu Leu Asn Gly Asp
245 250 255Ile71249PRTZea mays
71Met Gly Lys Leu Thr Leu Gly His Arg Gly Glu Ala Ser Glu Pro Asp1
5 10 15Phe Phe Arg Gly Val Leu
Gly Glu Leu Val Leu Thr Phe Leu Phe Val 20 25
30Phe Ile Gly Val Gly Ala Ala Met Thr Asp Gly Ala Thr
Thr Lys Gly 35 40 45Ser Thr Ala
Gly Gly Asp Leu Thr Ala Val Ala Leu Gly Gln Ala Leu 50
55 60Val Val Ala Val Ile Ala Thr Ala Gly Phe His Ile
Ser Gly Gly His65 70 75
80Val Asn Pro Ala Val Thr Leu Ser Leu Ala Val Gly Gly His Val Thr
85 90 95Leu Phe Arg Ser Ser Leu
Tyr Ile Ala Ala Gln Met Leu Ala Ser Ser 100
105 110Ala Ala Cys Phe Leu Leu Arg Trp Leu Thr Gly Gly
Leu Ala Thr Pro 115 120 125Val His
Ala Leu Ala Glu Gly Val Gly Pro Leu Gln Gly Val Val Ala 130
135 140Glu Ala Val Phe Thr Phe Ser Leu Leu Phe Val
Ile Tyr Ala Thr Ile145 150 155
160Leu Asp Pro Arg Lys Leu Leu Pro Gly Ala Gly Pro Leu Leu Thr Gly
165 170 175Leu Leu Val Gly
Ala Asn Ser Val Ala Gly Ala Ala Leu Ser Gly Ala 180
185 190Ser Met Asn Pro Ala Arg Ser Phe Gly Pro Ala
Val Ala Ser Gly Val 195 200 205Trp
Thr His His Trp Val Tyr Trp Val Gly Pro Leu Ala Gly Gly Pro 210
215 220Leu Ala Val Leu Val Tyr Glu Cys Cys Phe
Met Ala Ala Ala Pro Thr225 230 235
240His Asp Leu Leu Pro Gln Gln Asp Pro
24572252PRTZea mays 72Met Ala Lys Phe Ala Leu Gly His His Arg Glu Ala Ser
Asp Ala Gly1 5 10 15Cys
Val Arg Ala Val Leu Ala Glu Leu Ile Leu Thr Phe Leu Phe Val 20
25 30Phe Ala Gly Val Gly Ser Ala Met
Ala Thr Gly Lys Leu Ala Gly Gly 35 40
45Gly Gly Asp Thr Val Val Gly Leu Thr Ala Val Ala Leu Ala His Thr
50 55 60Leu Val Val Ala Val Met Val Ser
Ala Gly Leu His Val Ser Gly Gly65 70 75
80His Ile Asn Pro Ala Val Thr Leu Gly Leu Ala Ala Thr
Gly Arg Ile 85 90 95Thr
Leu Phe Arg Ser Ala Leu Tyr Val Ala Ala Gln Leu Leu Gly Ser
100 105 110Thr Leu Ala Cys Leu Leu Leu
Ala Phe Leu Ala Val Ala Asp Ser Gly 115 120
125Val Pro Val His Ala Leu Gly Ala Gly Val Gly Ala Leu Arg Gly
Val 130 135 140Leu Met Glu Ala Val Leu
Thr Phe Ser Leu Leu Phe Ala Val Tyr Ala145 150
155 160Thr Val Val Asp Pro Arg Arg Ala Val Gly Gly
Met Gly Pro Leu Leu 165 170
175Val Gly Leu Val Val Gly Ala Asn Val Leu Ala Gly Gly Pro Phe Ser
180 185 190Gly Ala Ser Met Asn Pro
Ala Arg Ser Phe Gly Pro Ala Leu Val Ala 195 200
205Gly Val Trp Ala Asp His Trp Val Tyr Trp Val Gly Pro Leu
Ile Gly 210 215 220Gly Pro Leu Ala Gly
Leu Val Tyr Asp Gly Leu Phe Met Ala Gln Gly225 230
235 240Gly His Glu Pro Leu Pro Arg Asp Asp Thr
Asp Phe 245 25073256PRTArabidopsis
thaliana 73Met Arg Arg Met Ile Pro Thr Ser Phe Ser Ser Lys Phe Gln Gly
Val1 5 10 15Leu Ser Met
Asn Ala Leu Arg Cys Tyr Val Ser Glu Phe Ile Ser Thr 20
25 30Phe Phe Phe Val Leu Ala Ala Val Gly Ser
Val Met Ser Ser Arg Lys 35 40
45Leu Met Ala Gly Asp Val Ser Gly Pro Phe Gly Val Leu Ile Pro Ala 50
55 60Ile Ala Asn Ala Leu Ala Leu Ser Ser
Ser Val Tyr Ile Ser Trp Asn65 70 75
80Val Ser Gly Gly His Val Asn Pro Ala Val Thr Phe Ala Met
Ala Val 85 90 95Ala Gly
Arg Ile Ser Val Pro Thr Ala Met Phe Tyr Trp Thr Ser Gln 100
105 110Met Ile Ala Ser Val Met Ala Cys Leu
Val Leu Lys Val Thr Val Met 115 120
125Glu Gln His Val Pro Ile Tyr Lys Ile Ala Gly Glu Met Thr Gly Phe
130 135 140Gly Ala Ser Val Leu Glu Gly
Val Leu Ala Phe Val Leu Val Tyr Thr145 150
155 160Val Phe Thr Ala Ser Asp Pro Arg Arg Gly Leu Pro
Leu Ala Val Gly 165 170
175Pro Ile Phe Ile Gly Phe Val Ala Gly Ala Asn Val Leu Ala Ala Gly
180 185 190Pro Phe Ser Gly Gly Ser
Met Asn Pro Ala Cys Ala Phe Gly Ser Ala 195 200
205Met Val Tyr Gly Ser Phe Lys Asn Gln Ala Val Tyr Trp Val
Gly Pro 210 215 220Leu Leu Gly Gly Ala
Thr Ala Ala Leu Val Tyr Asp Asn Val Val Val225 230
235 240Pro Val Glu Asp Asp Arg Gly Ser Ser Thr
Gly Asp Ala Ile Gly Val 245 250
25574296PRTArabidopsis thaliana 74Met Ala Asp Ile Ser Gly Asn Gly
Tyr Gly Asn Ala Arg Glu Glu Val1 5 10
15Val Met Val Asn Leu Lys Asp Glu Val Glu His Gln Gln Glu
Met Glu 20 25 30Asp Ile His
Asn Pro Arg Pro Leu Lys Lys Gln Asp Ser Leu Leu Ser 35
40 45Val Ser Val Pro Phe Leu Gln Lys Leu Ile Ala
Glu Phe Leu Gly Thr 50 55 60Tyr Phe
Leu Val Phe Thr Gly Cys Ala Ser Val Val Val Asn Met Gln65
70 75 80Asn Asp Asn Val Val Thr Leu
Pro Gly Ile Ala Ile Val Trp Gly Leu 85 90
95Thr Ile Met Val Leu Ile Tyr Ser Leu Gly His Ile Ser
Gly Ala His 100 105 110Ile Asn
Pro Ala Val Thr Ile Ala Phe Ala Ser Cys Gly Arg Phe Pro 115
120 125Leu Lys Gln Val Pro Ala Tyr Val Ile Ser
Gln Val Ile Gly Ser Thr 130 135 140Leu
Ala Ala Ala Thr Leu Arg Leu Leu Phe Gly Leu Asp His Asp Val145
150 155 160Cys Ser Gly Lys His Asp
Val Phe Ile Gly Ser Ser Pro Val Gly Ser 165
170 175Asp Leu Gln Ala Phe Thr Met Glu Phe Ile Val Thr
Phe Tyr Leu Met 180 185 190Phe
Ile Ile Ser Gly Val Ala Thr Asp Asn Arg Ala Ile Gly Glu Leu 195
200 205Ala Gly Leu Ala Ile Gly Ser Thr Val
Leu Leu Asn Val Leu Ile Ala 210 215
220Ala Pro Val Ser Ser Ala Ser Met Asn Pro Gly Arg Ser Leu Gly Pro225
230 235 240Ala Leu Val Tyr
Gly Cys Tyr Lys Gly Ile Trp Ile Tyr Leu Val Ala 245
250 255Pro Thr Leu Gly Ala Ile Ala Gly Ala Trp
Val Tyr Asn Thr Val Arg 260 265
270Tyr Thr Asp Lys Pro Leu Arg Glu Ile Thr Lys Ser Gly Ser Phe Leu
275 280 285Lys Thr Val Arg Ile Gly Ser
Thr 290 29575294PRTArabidopsis thaliana 75Met Ala Glu
Ile Ser Gly Asn Gly Gly Asp Ala Arg Asp Gly Ala Val1 5
10 15Val Val Asn Leu Lys Glu Glu Asp Glu
Gln Gln Gln Gln Gln Gln Ala 20 25
30Ile His Lys Pro Leu Lys Lys Gln Asp Ser Leu Leu Ser Ile Ser Val
35 40 45Pro Phe Leu Gln Lys Leu Met
Ala Glu Val Leu Gly Thr Tyr Phe Leu 50 55
60 Ile Phe Ala Gly Cys Ala Ala Val Ala Val Asn Thr Gln His Asp Lys65
70 75 80Ala Val Thr
Leu Pro Gly Ile Ala Ile Val Trp Gly Leu Thr Val Met 85
90 95Val Leu Val Tyr Ser Leu Gly His Ile
Ser Gly Ala His Phe Asn Pro 100 105
110Ala Val Thr Ile Ala Phe Ala Ser Cys Gly Arg Phe Pro Leu Lys Gln
115 120 125Val Pro Ala Tyr Val Ile
Ser Gln Val Ile Gly Ser Thr Leu Ala Ala 130 135
140Ala Thr Leu Arg Leu Leu Phe Gly Leu Asp Gln Asp Val Cys Ser
Gly145 150 155 160Lys His
Asp Val Phe Val Gly Thr Leu Pro Ser Gly Ser Asn Leu Gln
165 170 175Ser Phe Val Ile Glu Phe Ile
Ile Thr Phe Tyr Leu Met Phe Val Ile 180 185
190Ser Gly Val Ala Thr Asp Asn Arg Ala Ile Gly Glu Leu Ala
Gly Leu 195 200 205Ala Val Gly Ser
Thr Val Leu Leu Asn Val Ile Ile Ala Gly Pro Val 210
215 220Ser Gly Ala Ser Met Asn Pro Gly Arg Ser Leu Gly
Pro Ala Met Val225 230 235
240Tyr Ser Cys Tyr Arg Gly Leu Trp Ile Tyr Ile Val Ser Pro Ile Val
245 250 255Gly Ala Val Ser Gly
Ala Trp Val Tyr Asn Met Val Arg Tyr Thr Asp 260
265 270Lys Pro Leu Arg Glu Ile Thr Lys Ser Gly Ser Phe
Leu Lys Thr Val 275 280 285Arg Asn
Gly Ser Ser Arg 29076288PRTArabidopsis thaliana 76Met Asp Asp Ile Ser
Val Ser Lys Ser Asn His Gly Asn Val Val Val1 5
10 15Leu Asn Ile Lys Ala Ser Ser Leu Ala Asp Thr
Ser Leu Pro Ser Asn 20 25
30Lys His Glu Ser Ser Ser Pro Pro Leu Leu Ser Val His Phe Leu Gln
35 40 45Lys Leu Leu Ala Glu Leu Val Gly
Thr Tyr Tyr Leu Ile Phe Ala Gly 50 55
60Cys Ala Ala Ile Ala Val Asn Ala Gln His Asn His Val Val Thr Leu65
70 75 80Val Gly Ile Ala Val
Val Trp Gly Ile Val Ile Met Val Leu Val Tyr 85
90 95Cys Leu Gly His Leu Ser Ala His Phe Asn Pro
Ala Val Thr Leu Ala 100 105
110Leu Ala Ser Ser Gln Arg Phe Pro Leu Asn Gln Val Pro Ala Tyr Ile
115 120 125Thr Val Gln Val Ile Gly Ser
Thr Leu Ala Ser Ala Thr Leu Arg Leu 130 135
140Leu Phe Asp Leu Asn Asn Asp Val Cys Ser Lys Lys His Asp Val
Phe145 150 155 160Leu Gly
Ser Ser Pro Ser Gly Ser Asp Leu Gln Ala Phe Val Met Glu
165 170 175Phe Ile Ile Thr Gly Phe Leu
Met Leu Val Val Cys Ala Val Thr Thr 180 185
190Thr Lys Arg Thr Thr Glu Glu Leu Glu Gly Leu Ile Ile Gly
Ala Thr 195 200 205Val Thr Leu Asn
Val Ile Phe Ala Gly Glu Val Ser Gly Ala Ser Met 210
215 220Asn Pro Ala Arg Ser Ile Gly Pro Ala Leu Val Trp
Gly Cys Tyr Lys225 230 235
240Gly Ile Trp Ile Tyr Leu Leu Ala Pro Thr Leu Gly Ala Val Ser Gly
245 250 255Ala Leu Ile His Lys
Met Leu Pro Ser Ile Gln Asn Ala Glu Pro Glu 260
265 270Phe Ser Lys Thr Gly Ser Ser His Lys Arg Val Thr
Asp Leu Pro Leu 275 280
28577323PRTArabidopsis thaliana 77Met Ala Glu Ile Ser Asp Ile Thr Thr Gln
Thr Gln Thr Val Val Leu1 5 10
15Asp Ile Glu Asn Tyr Gln Ser Ile Asp Asp Ser Arg Ser Ser Asp Leu
20 25 30Ser Ala Pro Leu Val Ser
Val Ser Phe Val Gln Lys Leu Ile Gly Glu 35 40
45Phe Val Gly Thr Phe Thr Met Ile Phe Ala Gly Cys Ser Ala
Ile Val 50 55 60Val Asn Glu Thr Tyr
Gly Lys Pro Val Thr Leu Pro Gly Ile Ala Leu65 70
75 80Val Trp Gly Leu Val Val Thr Val Met Ile
Tyr Ser Ile Gly His Val 85 90
95Ser Gly Ala His Phe Asn Pro Ala Val Ser Ile Ala Phe Ala Ser Ser
100 105 110Lys Lys Phe Pro Phe
Asn Gln Val Pro Gly Tyr Ile Ala Ala Gln Leu 115
120 125Leu Gly Ser Thr Leu Ala Ala Ala Val Leu Arg Leu
Val Phe His Leu 130 135 140Asp Asp Asp
Val Cys Ser Leu Lys Gly Asp Val Tyr Val Gly Thr Tyr145
150 155 160Pro Ser Asn Ser Asn Thr Thr
Ser Phe Val Met Glu Phe Ile Ala Thr 165
170 175Phe Asn Leu Met Phe Val Ile Ser Ala Val Ala Thr
Asp Lys Arg Ala 180 185 190Thr
Gly Ser Phe Ala Gly Ile Ala Ile Gly Ala Thr Ile Val Leu Asp 195
200 205Ile Leu Phe Ser Gly Pro Ile Ser Gly
Ala Ser Met Asn Pro Ala Arg 210 215
220Ser Leu Gly Pro Ala Leu Ile Trp Gly Cys Tyr Lys Asp Leu Trp Leu225
230 235 240Tyr Ile Val Ser
Pro Val Ile Gly Ala Leu Ser Gly Ala Trp Thr Tyr 245
250 255Gly Leu Leu Arg Ser Thr Lys Lys Ser Tyr
Ser Glu Ile Ile Arg Pro 260 265
270Asn Cys Asn Lys Val Ser Ser Arg Asp Arg Gln Glu Ala Ser Gln Asp
275 280 285Glu Ile Cys Val Leu Arg Val
Val Asp Pro Ala Asn Gln Asn Tyr Phe 290 295
300Ile Cys Ser Ser Pro Thr Asp Ile Asn Gly Lys Cys Asn Val Thr
Cys305 310 315 320Lys Leu
Ala78282PRTZea mays 78Met Ala Gly Gly Gly Asp His Ser Gln Thr Asn Gly Gly
His Val Asp1 5 10 15Gln
Arg Ala Leu Glu Glu Gly Arg Lys Glu Glu Phe Ala Asp Gln Gly 20
25 30Cys Ala Ala Met Val Val Ser Val
Pro Phe Ile Gln Lys Ile Ile Ala 35 40
45Glu Ile Phe Gly Thr Tyr Phe Leu Met Phe Ala Gly Cys Gly Ala Val
50 55 60Thr Ile Asn Ala Ser Lys Asn Gly
Gln Ile Thr Phe Pro Gly Val Ala65 70 75
80Ile Val Trp Gly Leu Ala Val Met Val Met Val Tyr Ala
Val Gly His 85 90 95Ile
Ser Gly Ala His Phe Asn Pro Ala Val Thr Leu Ala Phe Ala Thr
100 105 110Ser Gly Arg Phe Pro Trp Arg
Gln Leu Pro Ala Tyr Val Leu Ala Gln 115 120
125Met Leu Gly Ala Thr Leu Ala Ser Gly Thr Leu Arg Leu Met Phe
Gly 130 135 140Gly Arg His Glu His Phe
Pro Gly Thr Leu Pro Thr Gly Ser Glu Val145 150
155 160Gln Ser Leu Val Ile Glu Ile Ile Thr Thr Phe
Tyr Leu Met Phe Val 165 170
175Ile Ser Gly Val Ala Thr Asp Asn Arg Ala Ile Gly Glu Leu Ala Gly
180 185 190Leu Ala Val Gly Ala Thr
Ile Leu Leu Asn Val Leu Ile Ala Gly Pro 195 200
205Val Ser Gly Ala Ser Met Asn Pro Ala Arg Ser Val Gly Pro
Ala Leu 210 215 220Val Ser Gly Glu Tyr
Thr Ser Ile Trp Val Tyr Val Val Gly Pro Val225 230
235 240Val Gly Ala Val Ala Gly Ala Trp Ala Tyr
Asn Leu Ile Arg Phe Thr 245 250
255Asn Lys Pro Leu Arg Glu Ile Thr Lys Ser Thr Ser Phe Leu Lys Ser
260 265 270Thr Ser Arg Met Asn
Ser Ala Ala Ser Ala 275 28079294PRTZea mays 79Met
Ala Ala Ala Ser Thr Thr Ser Arg Thr Asn Ser Arg Val Asn Tyr1
5 10 15Ser Asn Glu Ile His Asp Leu
Ser Thr Val Gln Ser Gly Ser Val Val 20 25
30Pro Thr Leu Phe Tyr Pro Asp Lys Ser Ile Ala Asp Ile Phe
Pro Pro 35 40 45His Leu Gly Lys
Lys Val Ile Ser Glu Val Val Ala Thr Phe Leu Leu 50 55
60Val Phe Val Thr Cys Gly Ala Ala Ser Ile Tyr Gly Glu
Asp Asn Arg65 70 75
80Arg Ile Ser Gln Leu Gly Gln Ser Val Ala Gly Gly Leu Ile Val Thr
85 90 95Val Met Ile Tyr Ala Thr
Gly His Ile Ser Gly Ala His Met Asn Pro 100
105 110Ala Val Thr Leu Ser Phe Ala Cys Phe Arg His Phe
Pro Trp Ile Gln 115 120 125Val Pro
Phe Tyr Trp Ala Ala Gln Phe Thr Gly Ala Met Cys Ala Ala 130
135 140Phe Val Leu Lys Ala Val Leu His Pro Ile Ala
Val Ile Gly Thr Thr145 150 155
160Thr Pro Ser Gly Pro His Trp His Ala Leu Leu Ile Glu Ile Val Val
165 170 175Thr Phe Asn Met
Met Phe Val Thr Cys Ala Val Ala Thr Asp Ser Arg 180
185 190Ala Val Gly Glu Leu Ala Gly Leu Ala Val Gly
Ser Ala Val Cys Ile 195 200 205Thr
Ser Ile Phe Ala Gly Pro Val Ser Gly Gly Ser Met Asn Pro Ala 210
215 220Arg Thr Leu Ala Pro Ala Val Ala Ser Asn
Val Phe Thr Gly Leu Trp225 230 235
240Ile Tyr Phe Leu Gly Pro Val Ile Gly Thr Leu Ser Gly Ala Trp
Val 245 250 255Tyr Thr Tyr
Ile Arg Phe Glu Glu Ala Pro Ala Ala Lys Asp Thr Gln 260
265 270Arg Leu Ser Ser Phe Lys Leu Arg Arg Met
Gln Ser Gln Leu Ala Ala 275 280
285Asp Glu Phe Asp Thr Val 29080301PRTZea mays 80Met Ala Ala Ser Thr
Thr Ser Arg Thr Asn Ser Arg Val Asn Tyr Ser1 5
10 15Asn Glu Ile His Asp Leu Ser Thr Val Gln Gly
Gly Ser Ala Ala Ala 20 25
30Ala Ala Ala Ala Leu Phe Tyr Pro Asp Ser Lys Ser Ile Ala Asp Ile
35 40 45Phe Pro Pro His Leu Gly Lys Lys
Val Ile Ser Glu Val Val Ala Thr 50 55
60Phe Leu Leu Val Phe Val Thr Cys Gly Ala Ala Ser Ile Tyr Gly Glu65
70 75 80Asp Asn Ala Arg Ile
Ser Gln Leu Gly Gln Ser Val Ala Gly Gly Leu 85
90 95Ile Val Thr Val Met Ile Tyr Ala Thr Gly His
Ile Ser Gly Ala His 100 105
110Met Asn Pro Ala Val Thr Leu Ser Phe Ala Cys Phe Arg His Phe Pro
115 120 125Trp Ile Gln Val Pro Phe Tyr
Trp Ala Ala Gln Phe Thr Gly Ala Met 130 135
140Cys Ala Ala Phe Val Leu Lys Ala Val Leu Gln Pro Ile Ala Val
Ile145 150 155 160Gly Thr
Thr Thr Pro Ser Gly Pro His Trp His Ala Leu Ala Ile Glu
165 170 175Ile Val Val Thr Phe Asn Met
Met Phe Val Thr Cys Ala Val Ala Thr 180 185
190Asp Ser Arg Ala Val Gly Glu Leu Ala Gly Leu Ala Val Gly
Ser Ala 195 200 205Val Cys Ile Thr
Ser Ile Phe Ala Gly Pro Val Ser Gly Gly Ser Met 210
215 220Asn Pro Ala Arg Thr Leu Ala Pro Ala Val Ala Ser
Asn Val Phe Thr225 230 235
240Gly Leu Trp Ile Tyr Phe Leu Gly Pro Val Val Gly Thr Leu Ser Gly
245 250 255Ala Trp Val Tyr Thr
Tyr Ile Arg Phe Glu Glu Ala Pro Ala Ala Ala 260
265 270Lys Pro Asp Thr Gln Arg Leu Ser Ser Phe Lys Leu
Arg Arg Met Gln 275 280 285Ser Gln
Ser Ala Leu Ala Ala Asp Glu Phe Asp Thr Val 290 295
30081283PRTArabidopsis thaliana 81Met Ser Ser His Ser Asp
Glu Ile Glu Glu Glu Gln Ile Ser Arg Ile1 5
10 15Glu Lys Gly Lys Gly Lys Asp Cys Gln Gly Gly Ile
Glu Thr Val Ile 20 25 30Cys
Thr Ser Pro Ser Ile Val Cys Leu Thr Gln Lys Leu Ile Ala Glu 35
40 45Met Ile Gly Thr Tyr Phe Ile Val Phe
Ser Gly Cys Gly Val Val Val 50 55
60Val Asn Val Leu Tyr Gly Gly Thr Ile Thr Phe Pro Gly Ile Cys Val65
70 75 80Thr Trp Gly Leu Ile
Val Met Val Met Ile Tyr Ser Thr Gly His Ile 85
90 95Ser Gly Ala His Phe Asn Pro Ala Val Thr Val
Thr Phe Ala Ile Phe 100 105
110Arg Arg Phe Pro Trp His Gln Val Pro Leu Tyr Ile Gly Ala Gln Phe
115 120 125Ala Gly Ser Leu Leu Ala Ser
Leu Thr Leu Arg Leu Met Phe Lys Val 130 135
140Thr Pro Glu Ala Phe Phe Gly Thr Thr Pro Ala Asp Ser Pro Ala
Arg145 150 155 160Ala Leu
Val Ala Glu Ile Ile Ile Ser Phe Leu Leu Met Phe Val Ile
165 170 175Ser Gly Val Ala Thr Asp Asn
Arg Ala Val Gly Glu Leu Ala Gly Ile 180 185
190Ala Val Gly Met Thr Ile Met Val Asn Val Phe Val Ala Gly
Pro Ile 195 200 205Ser Gly Ala Ser
Met Asn Pro Ala Arg Ser Leu Gly Pro Ala Leu Val 210
215 220Met Gly Val Tyr Lys His Ile Trp Val Tyr Ile Val
Gly Pro Val Leu225 230 235
240Gly Val Ile Ser Gly Gly Phe Val Tyr Asn Leu Ile Arg Phe Thr Asp
245 250 255Lys Pro Leu Arg Glu
Leu Thr Lys Ser Ala Ser Phe Leu Arg Ala Val 260
265 270Ser Pro Ser His Lys Gly Ser Ser Ser Lys Thr
275 28082283PRTArabidopsis thaliana 82Met Thr Ser His
Gly Glu Glu Ile Glu Asp Glu Gln Ile Ser Arg Ile1 5
10 15Glu Lys Gly Asn Cys Lys Asp Ser Gln Gly
Gly Met Glu Thr Ala Ile 20 25
30Cys Ser Ser Pro Ser Ile Val Cys Leu Thr Gln Lys Leu Ile Ala Glu
35 40 45Met Ile Gly Thr Tyr Phe Ile Ile
Phe Ser Gly Cys Gly Val Val Val 50 55
60Val Asn Val Leu Tyr Gly Gly Thr Ile Thr Phe Pro Gly Ile Cys Val65
70 75 80Thr Trp Gly Leu Ile
Val Met Val Met Ile Tyr Ser Thr Gly His Ile 85
90 95Ser Gly Ala His Phe Asn Pro Ala Val Thr Val
Thr Phe Ala Val Phe 100 105
110Arg Arg Phe Pro Trp Tyr Gln Val Pro Leu Tyr Ile Gly Ala Gln Leu
115 120 125Thr Gly Ser Leu Leu Ala Ser
Leu Thr Leu Arg Leu Met Phe Asn Val 130 135
140Thr Pro Lys Ala Phe Phe Gly Thr Thr Pro Thr Asp Ser Ser Gly
Gln145 150 155 160Ala Leu
Val Ala Glu Ile Ile Ile Ser Phe Leu Leu Met Phe Val Ile
165 170 175Ser Gly Val Ala Thr Asp Ser
Arg Ala Thr Gly Glu Leu Ala Gly Ile 180 185
190Ala Val Gly Met Thr Ile Ile Leu Asn Val Phe Val Ala Gly
Pro Ile 195 200 205Ser Gly Ala Ser
Met Asn Pro Ala Arg Ser Leu Gly Pro Ala Ile Val 210
215 220Met Gly Arg Tyr Lys Gly Ile Trp Val Tyr Ile Val
Gly Pro Phe Val225 230 235
240Gly Ile Phe Ala Gly Gly Phe Val Tyr Asn Phe Met Arg Phe Thr Asp
245 250 255Lys Pro Leu Arg Glu
Leu Thr Lys Ser Ala Ser Phe Leu Arg Ser Val 260
265 270Ala Gln Lys Asp Asn Ala Ser Lys Ser Asp Gly
275 28083304PRTArabidopsis thaliana 83Met Ala Pro Pro
Glu Ala Glu Val Gly Ala Val Met Val Met Ala Pro1 5
10 15Pro Thr Pro Gly Thr Pro Gly Thr Pro Gly
Gly Pro Leu Ile Thr Gly 20 25
30Met Arg Val Asp Ser Met Ser Phe Asp His Arg Lys Pro Thr Pro Arg
35 40 45Cys Lys Cys Leu Pro Val Met Gly
Ser Thr Trp Gly Gln His Asp Thr 50 55
60Cys Phe Thr Asp Phe Pro Ser Pro Asp Val Ser Leu Thr Arg Lys Leu65
70 75 80Gly Ala Glu Phe Val
Gly Thr Phe Ile Leu Ile Phe Thr Ala Thr Ala 85
90 95Gly Pro Ile Val Asn Gln Lys Tyr Asp Gly Ala
Glu Thr Leu Ile Gly 100 105
110Asn Ala Ala Cys Ala Gly Leu Ala Val Met Ile Ile Ile Leu Ser Thr
115 120 125Gly His Ile Ser Gly Ala His
Leu Asn Pro Ser Leu Thr Ile Ala Phe 130 135
140Ala Ala Leu Arg His Phe Pro Trp Ala His Val Pro Ala Tyr Ile
Ala145 150 155 160Ala Gln
Val Ser Ala Ser Ile Cys Ala Ser Phe Ala Leu Lys Gly Val
165 170 175Phe His Pro Phe Met Ser Gly
Gly Val Thr Ile Pro Ser Val Ser Leu 180 185
190Gly Gln Ala Phe Ala Leu Glu Phe Ile Ile Thr Phe Ile Leu
Leu Phe 195 200 205Val Val Thr Ala
Val Ala Thr Asp Thr Arg Ala Val Gly Glu Leu Ala 210
215 220Gly Ile Ala Val Gly Ala Thr Val Met Leu Asn Ile
Leu Val Ala Gly225 230 235
240Pro Ser Thr Gly Gly Ser Met Asn Pro Val Arg Thr Leu Gly Pro Ala
245 250 255Val Ala Ser Gly Asn
Tyr Arg Ser Leu Trp Val Tyr Leu Val Ala Pro 260
265 270Thr Leu Gly Ala Ile Ser Gly Ala Ala Val Tyr Thr
Gly Val Lys Leu 275 280 285Asn Asp
Ser Val Thr Asp Pro Pro Arg Pro Val Arg Ser Phe Arg Arg 290
295 30084305PRTArabidopsis thaliana 84Met Asp His
Glu Glu Ile Pro Ser Thr Pro Ser Thr Pro Ala Thr Thr1 5
10 15Pro Gly Thr Pro Gly Ala Pro Leu Phe
Gly Gly Phe Glu Gly Lys Arg 20 25
30Asn Gly His Asn Gly Arg Tyr Thr Pro Lys Ser Leu Leu Lys Ser Cys
35 40 45Lys Cys Phe Ser Val Asp Asn
Glu Trp Ala Leu Glu Asp Gly Arg Leu 50 55
60Pro Pro Val Thr Cys Ser Leu Pro Pro Pro Asn Val Ser Leu Tyr Arg65
70 75 80Lys Leu Gly Ala
Glu Phe Val Gly Thr Leu Ile Leu Ile Phe Ala Gly 85
90 95Thr Ala Thr Ala Ile Val Asn Gln Lys Thr
Asp Gly Ala Glu Thr Leu 100 105
110Ile Gly Cys Ala Ala Ser Ala Gly Leu Ala Val Met Ile Val Ile Leu
115 120 125Ser Thr Gly His Ile Ser Gly
Ala His Leu Asn Pro Ala Val Thr Ile 130 135
140Ala Phe Ala Ala Leu Lys His Phe Pro Trp Lys His Val Pro Val
Tyr145 150 155 160Ile Gly
Ala Gln Val Met Ala Ser Val Ser Ala Ala Phe Ala Leu Lys
165 170 175Ala Val Phe Glu Pro Thr Met
Ser Gly Gly Val Thr Val Pro Thr Val 180 185
190Gly Leu Ser Gln Ala Phe Ala Leu Glu Phe Ile Ile Ser Phe
Asn Leu 195 200 205Met Phe Val Val
Thr Ala Val Ala Thr Asp Thr Arg Ala Val Gly Glu 210
215 220Leu Ala Gly Ile Ala Val Gly Ala Thr Val Met Leu
Asn Ile Leu Ile225 230 235
240Ala Gly Pro Ala Thr Ser Ala Ser Met Asn Pro Val Arg Thr Leu Gly
245 250 255Pro Ala Ile Ala Ala
Asn Asn Tyr Arg Ala Ile Trp Val Tyr Leu Thr 260
265 270Ala Pro Ile Leu Gly Ala Leu Ile Gly Ala Gly Thr
Tyr Thr Ile Val 275 280 285Lys Leu
Pro Glu Glu Asp Glu Ala Pro Lys Glu Arg Arg Ser Phe Arg 290
295 300Arg30585275PRTArabidopsis thaliana 85Met Asn
Gly Glu Ala Arg Ser Arg Val Val Asp Gln Glu Ala Gly Ser1 5
10 15Thr Pro Ser Thr Leu Arg Asp Glu
Asp His Pro Ser Arg Gln Arg Leu 20 25
30Phe Gly Cys Leu Pro Tyr Asp Ile Asp Leu Asn Pro Leu Arg Ile
Val 35 40 45Met Ala Glu Leu Val
Gly Thr Phe Ile Leu Met Phe Ser Val Cys Gly 50 55
60Val Ile Ser Ser Thr Gln Leu Ser Gly Gly His Val Gly Leu
Leu Glu65 70 75 80Tyr
Ala Val Thr Ala Gly Leu Ser Val Val Val Val Val Tyr Ser Ile
85 90 95Gly His Ile Ser Gly Ala His
Leu Asn Pro Ser Ile Thr Ile Ala Phe 100 105
110Ala Val Phe Gly Gly Phe Pro Trp Ser Gln Val Pro Leu Tyr
Ile Thr 115 120 125Ala Gln Thr Leu
Gly Ala Thr Ala Ala Thr Leu Val Gly Val Ser Val 130
135 140Tyr Gly Val Asn Ala Asp Ile Met Ala Thr Lys Pro
Ala Leu Ser Cys145 150 155
160Val Ser Ala Phe Phe Val Glu Leu Ile Ala Thr Ser Ile Val Val Phe
165 170 175Leu Ala Ser Ala Leu
His Cys Gly Pro His Gln Asn Leu Gly Asn Leu 180
185 190Thr Gly Phe Val Ile Gly Thr Val Ile Ser Leu Gly
Val Leu Ile Thr 195 200 205Gly Pro
Ile Ser Gly Gly Ser Met Asn Pro Ala Arg Ser Leu Gly Pro 210
215 220Ala Val Val Ala Trp Asp Phe Glu Asp Leu Trp
Ile Tyr Met Thr Ala225 230 235
240Pro Val Ile Gly Ala Ile Ile Gly Val Leu Thr Tyr Arg Ser Ile Ser
245 250 255Leu Lys Thr Arg
Pro Cys Pro Ser Pro Val Ser Pro Ser Val Ser Ser 260
265 270Leu Leu Arg 27586302PRTZea mays 86Met
Glu Pro Gly Ser Thr Pro Pro Asn Gly Ser Ala Pro Ala Thr Pro1
5 10 15Gly Thr Pro Ala Pro Leu Phe
Ser Ser Gly Gly Pro Arg Val Asp Ser 20 25
30Leu Ser Tyr Glu Arg Lys Ser Met Pro Arg Cys Lys Cys Leu
Pro Leu 35 40 45Pro Ala Val Glu
Gly Trp Gly Val Ala Thr His Thr Cys Val Val Glu 50 55
60Ile Pro Ala Pro Asp Val Ser Leu Thr Arg Lys Leu Gly
Ala Glu Phe65 70 75
80Val Gly Thr Phe Ile Leu Ile Phe Phe Ala Thr Ala Ala Pro Ile Val
85 90 95Asn Gln Lys Tyr Gly Gly
Ala Ile Ser Pro Phe Gly Asn Ala Ala Cys 100
105 110Ala Gly Leu Ala Val Ala Thr Val Ile Leu Ser Thr
Gly His Ile Ser 115 120 125Gly Ala
His Leu Asn Pro Ser Leu Thr Ile Ala Phe Ala Ala Leu Arg 130
135 140His Phe Pro Trp Leu Gln Val Pro Ala Tyr Val
Ala Val Gln Ala Leu145 150 155
160Ala Ser Val Cys Ala Ala Phe Ala Leu Lys Gly Val Phe His Pro Phe
165 170 175Leu Ser Gly Gly
Val Thr Val Pro Asp Ala Thr Val Ser Thr Ala Gln 180
185 190Ala Phe Phe Thr Glu Phe Ile Ile Ser Phe Asn
Leu Leu Phe Val Val 195 200 205Thr
Ala Val Ala Thr Asp Thr Arg Ala Val Gly Glu Leu Ala Gly Ile 210
215 220Ala Val Gly Ala Ala Val Thr Leu Asn Ile
Leu Val Ala Gly Pro Thr225 230 235
240Thr Gly Gly Ser Met Asn Pro Val Arg Thr Leu Gly Pro Ala Val
Ala 245 250 255Ala Gly Asn
Tyr Arg Gln Leu Trp Ile Tyr Leu Leu Ala Pro Thr Leu 260
265 270Gly Ala Leu Ala Gly Ala Ser Val Tyr Lys
Ala Val Lys Leu Arg Asp 275 280
285Glu Asn Gly Glu Thr Pro Arg Thr Gln Arg Ser Phe Arg Arg 290
295 30087240PRTArabidopsis thaliana 87Met Met Gly
Val Leu Lys Ser Ala Ile Gly Asp Met Leu Met Thr Phe1 5
10 15Ser Trp Val Val Leu Ser Ala Thr Phe
Gly Ile Gln Thr Ala Ala Ile 20 25
30Ile Ser Ala Gly Asp Phe Gln Ala Ile Thr Trp Ala Pro Leu Val Ile
35 40 45Leu Thr Ser Leu Ile Phe Val
Tyr Val Ser Ile Phe Thr Val Ile Phe 50 55
60Gly Ser Ala Ser Phe Asn Pro Thr Gly Ser Ala Ala Phe Tyr Val Ala65
70 75 80Gly Val Pro Gly
Asp Thr Leu Phe Ser Leu Ala Ile Arg Leu Pro Ala 85
90 95Gln Ala Ile Gly Ala Ala Gly Gly Ala Leu
Ala Ile Met Glu Phe Ile 100 105
110Pro Glu Lys Tyr Lys His Met Ile Gly Gly Pro Ser Leu Gln Val Asp
115 120 125Val His Thr Gly Ala Ile Ala
Glu Thr Ile Leu Ser Phe Gly Ile Thr 130 135
140Phe Ala Val Leu Leu Ile Ile Leu Arg Gly Pro Arg Arg Leu Leu
Ala145 150 155 160Lys Thr
Phe Leu Leu Ala Leu Ala Thr Ile Ser Phe Val Val Ala Gly
165 170 175Ser Lys Tyr Thr Gly Pro Ala
Met Asn Pro Ala Ile Ala Phe Gly Trp 180 185
190Ala Tyr Met Tyr Ser Ser His Asn Thr Trp Asp His Ile Tyr
Val Tyr 195 200 205Trp Ile Ser Ser
Phe Val Gly Ala Leu Ser Ala Ala Leu Leu Phe Arg 210
215 220Ser Ile Phe Pro Pro Pro Arg Pro Gln Lys Lys Lys
Gln Lys Lys Ala225 230 235
24088243PRTArabidopsis thaliana 88Met Ser Ala Val Lys Ser Ala Leu Gly
Asp Met Val Ile Thr Phe Leu1 5 10
15Trp Val Ile Leu Ser Ala Thr Phe Gly Ile Gln Thr Ala Ala Ile
Val 20 25 30Ser Ala Val Gly
Phe His Gly Ile Thr Trp Ala Pro Leu Val Ile Ser 35
40 45Thr Leu Val Val Phe Val Ser Ile Ser Ile Phe Thr
Val Ile Gly Asn 50 55 60Val Leu Gly
Gly Ala Ser Phe Asn Pro Cys Gly Asn Ala Ala Phe Tyr65 70
75 80Thr Ala Gly Val Ser Ser Asp Ser
Leu Phe Ser Leu Ala Ile Arg Ser 85 90
95Pro Ala Gln Ala Ile Gly Ala Ala Gly Gly Ala Ile Thr Ile
Met Glu 100 105 110Met Ile Pro
Glu Lys Tyr Lys Thr Arg Ile Gly Gly Lys Pro Ser Leu 115
120 125Gln Phe Gly Ala His Asn Gly Ala Ile Ser Glu
Val Val Leu Ser Phe 130 135 140Ser Val
Thr Phe Leu Val Leu Leu Ile Ile Leu Arg Gly Pro Arg Lys145
150 155 160Leu Leu Ala Lys Thr Phe Leu
Leu Ala Leu Ala Thr Val Ser Val Phe 165
170 175Val Val Gly Ser Lys Phe Thr Arg Pro Phe Met Asn
Pro Ala Ile Ala 180 185 190Phe
Gly Trp Ala Tyr Ile Tyr Lys Ser His Asn Thr Trp Asp His Phe 195
200 205Tyr Val Tyr Trp Ile Ser Ser Tyr Thr
Gly Ala Ile Leu Ser Ala Met 210 215
220Leu Phe Arg Ile Ile Phe Pro Ala Pro Pro Leu Val Gln Lys Lys Gln225
230 235 240Lys Lys
Ala89245PRTZea mays 89Met Ala Met Gly Ala Thr Val Arg Ala Ala Ala Ala Asp
Ala Val Val1 5 10 15Thr
Phe Leu Trp Val Leu Cys Ala Ser Ala Leu Gly Ala Ser Thr Ala 20
25 30Ala Val Thr Ser Tyr Leu Gly Val
Gln Glu Gly Ala Gly His Tyr Ala 35 40
45Leu Leu Val Thr Thr Ser Leu Leu Ser Val Leu Leu Phe Thr Phe Asp
50 55 60Leu Leu Cys Gly Ala Leu Gly Gly
Ala Ser Phe Asn Pro Thr Asp Phe65 70 75
80Ala Ala Ser Tyr Ala Ala Gly Leu Asp Ser Pro Ser Leu
Phe Ser Val 85 90 95Ala
Leu Arg Phe Pro Ala Gln Ala Ala Gly Ala Val Gly Gly Ala Leu
100 105 110Ala Ile Ser Glu Leu Met Pro
Ala Gln Tyr Lys His Thr Leu Ala Gly 115 120
125Pro Ser Leu Lys Val Asp Pro His Thr Gly Ala Leu Ala Glu Gly
Val 130 135 140Leu Thr Phe Val Ile Thr
Leu Thr Val Leu Trp Val Ile Val Lys Gly145 150
155 160Pro Arg Asn Val Ile Leu Lys Thr Leu Leu Leu
Ser Thr Ser Ile Val 165 170
175Ser Val Ile Leu Ala Gly Ala Glu Tyr Thr Gly Pro Ser Met Asn Pro
180 185 190Ala Asn Ala Phe Gly Trp
Ala Tyr Val Asn Asn Trp His Asn Thr Trp 195 200
205Glu Gln Leu Tyr Val Tyr Trp Ile Cys Pro Phe Ile Gly Ala
Met Leu 210 215 220Ala Gly Trp Ile Phe
Arg Val Val Phe Leu Pro Pro Ala Pro Lys Pro225 230
235 240Lys Thr Lys Lys Ala
24590243PRTZea mays 90Met Ala Met Gly Glu Ala Leu Arg Ala Ala Ala Ala Asp
Ala Val Val1 5 10 15Thr
Phe Leu Trp Val Leu Cys Val Ser Thr Leu Gly Ala Ser Thr Thr 20
25 30Ala Val Thr Ser Tyr Leu Arg Leu
Gln Gly Val His Phe Ala Leu Leu 35 40
45Val Thr Val Ser Leu Leu Ser Val Leu Leu Phe Val Phe Asn Ile Leu
50 55 60Cys Asp Ala Leu Gly Gly Ala Ser
Phe Asn Pro Thr Gly Val Ala Ala65 70 75
80Phe Tyr Ala Ala Gly Val Thr Ser Pro Ser Leu Phe Ser
Ile Ala Leu 85 90 95Arg
Leu Pro Ala Gln Ala Ala Gly Ala Val Gly Gly Ala Leu Ala Ile
100 105 110Ser Glu Leu Met Pro Ala Gln
Tyr Arg His Met Leu Gly Gly Pro Ser 115 120
125Leu Lys Val Asp Pro His Thr Gly Ala Gly Ala Glu Leu Val Leu
Thr 130 135 140Phe Val Ile Thr Leu Ala
Val Leu Leu Ile Ile Val Lys Gly Pro Arg145 150
155 160Asn Pro Ile Ile Lys Thr Trp Met Ile Ser Ile
Cys Thr Leu Cys Leu 165 170
175Val Leu Ser Gly Ala Ala Tyr Thr Gly Pro Ser Met Asn Pro Ala Asn
180 185 190Ala Phe Gly Trp Ala Tyr
Val Asn Asn Arg His Asn Thr Trp Glu Gln 195 200
205Phe Tyr Val Tyr Trp Ile Cys Pro Phe Ile Gly Ala Ile Leu
Ala Ala 210 215 220Trp Ile Phe Arg Ala
Met Phe Leu Thr Pro Pro Pro Lys Pro Lys Ala225 230
235 240Lys Lys Ala91237PRTArabidopsis thaliana
91Met Gly Arg Ile Gly Leu Val Val Thr Asp Leu Val Leu Ser Phe Met1
5 10 15Trp Ile Trp Ala Gly Val
Leu Val Asn Ile Leu Val His Gly Val Leu 20 25
30Gly Phe Ser Arg Thr Asp Pro Ser Gly Glu Ile Val Arg
Tyr Leu Phe 35 40 45Ser Ile Ile
Ser Met Phe Ile Phe Ala Tyr Leu Gln Gln Ala Thr Lys 50
55 60Gly Gly Leu Tyr Asn Pro Leu Thr Ala Leu Ala Ala
Gly Val Ser Gly65 70 75
80Gly Phe Ser Ser Phe Ile Phe Ser Val Phe Val Arg Ile Pro Val Glu
85 90 95Val Ile Gly Ser Ile Leu
Ala Val Lys His Ile Ile His Val Phe Pro 100
105 110Glu Ile Gly Lys Gly Pro Lys Leu Asn Val Ala Ile
His His Gly Ala 115 120 125Leu Thr
Glu Gly Ile Leu Thr Phe Phe Ile Val Leu Leu Ser Met Gly 130
135 140Leu Thr Arg Lys Ile Pro Gly Ser Phe Phe Met
Lys Thr Trp Ile Gly145 150 155
160Ser Leu Ala Lys Leu Thr Leu His Ile Leu Gly Ser Asp Leu Thr Gly
165 170 175Gly Cys Met Asn
Pro Ala Ala Val Met Gly Trp Ala Tyr Ala Arg Gly 180
185 190Glu His Ile Thr Lys Glu His Leu Leu Val Tyr
Trp Leu Gly Pro Val 195 200 205Lys
Ala Thr Leu Leu Ala Val Trp Phe Phe Lys Val Val Phe Lys Pro 210
215 220Leu Thr Glu Glu Gln Glu Lys Pro Lys Ala
Lys Ser Glu225 230 235
User Contributions:
Comment about this patent or add new information about this topic:
People who visited this patent also read: | |
Patent application number | Title |
---|---|
20110195955 | HIGHLY SELECTIVE SIGMA RECEPTOR LIGANDS |
20110195954 | NOVEL COMPOUNDS |
20110195953 | COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS |
20110195952 | TREATING PSYCHOLOGICAL CONDITIONS USING MUSCARINIC RECEPTOR M1 ANTAGONISTS |
20110195951 | DIAZAINDOLE DERIVATIVES AND THEIR USE IN THE INHIBITION OF C-JUN N-TERMINAL KINASE |