EPHA2_HUMAN
ID EPHA2_HUMAN Reviewed; 976 AA.
AC P29317; B5A968; Q8N3Z2;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 242.
DE RecName: Full=Ephrin type-A receptor 2;
DE EC=2.7.10.1;
DE AltName: Full=Epithelial cell kinase;
DE AltName: Full=Tyrosine-protein kinase receptor ECK;
DE Flags: Precursor;
GN Name=EPHA2; Synonyms=ECK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, AND
RP AUTOPHOSPHORYLATION.
RC TISSUE=Epithelium;
RX PubMed=2174105; DOI=10.1128/mcb.10.12.6316-6324.1990;
RA Lindberg R.A., Hunter T.;
RT "cDNA cloning and characterization of eck, an epithelial cell receptor
RT protein-tyrosine kinase in the eph/elk family of protein kinases.";
RL Mol. Cell. Biol. 10:6316-6324(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RX PubMed=18593464; DOI=10.1186/ar2447;
RA Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D.,
RA Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.;
RT "Novel splice variants derived from the receptor tyrosine kinase
RT superfamily are potential therapeutics for rheumatoid arthritis.";
RL Arthritis Res. Ther. 10:R73-R73(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NOMENCLATURE.
RX PubMed=9267020; DOI=10.1016/s0092-8674(00)80500-0;
RG Eph nomenclature committee;
RT "Unified nomenclature for Eph family receptors and their ligands, the
RT ephrins.";
RL Cell 90:403-404(1997).
RN [7]
RP FUNCTION IN INTEGRIN-MEDIATED CELL ADHESION, FUNCTION IN CELL MIGRATION,
RP PHOSPHORYLATION, INTERACTION WITH PTK2/FAK1 AND PTPN11, AND SUBCELLULAR
RP LOCATION.
RX PubMed=10655584; DOI=10.1038/35000008;
RA Miao H., Burnett E., Kinch M., Simon E., Wang B.;
RT "Activation of EphA2 kinase suppresses integrin function and causes focal-
RT adhesion-kinase dephosphorylation.";
RL Nat. Cell Biol. 2:62-69(2000).
RN [8]
RP ONCOGENICITY.
RX PubMed=11280802;
RA Zelinski D.P., Zantek N.D., Stewart J.C., Irizarry A.R., Kinch M.S.;
RT "EphA2 overexpression causes tumorigenesis of mammary epithelial cells.";
RL Cancer Res. 61:2301-2306(2001).
RN [9]
RP INTERACTION WITH ACP1, AND DEPHOSPHORYLATION BY ACP1.
RX PubMed=12167657; DOI=10.1074/jbc.m207127200;
RA Kikawa K.D., Vidale D.R., Van Etten R.L., Kinch M.S.;
RT "Regulation of the EphA2 kinase by the low molecular weight tyrosine
RT phosphatase induces transformation.";
RL J. Biol. Chem. 277:39274-39279(2002).
RN [10]
RP FUNCTION IN CELL-CELL INTERACTION, INTERACTION WITH CLDN4, AND MUTAGENESIS
RP OF LYS-646.
RX PubMed=16236711; DOI=10.1074/jbc.m503786200;
RA Tanaka M., Kamata R., Sakai R.;
RT "EphA2 phosphorylates the cytoplasmic tail of Claudin-4 and mediates
RT paracellular permeability.";
RL J. Biol. Chem. 280:42375-42382(2005).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=17332925;
RA Liu D.-P., Wang Y., Koeffler H.P., Xie D.;
RT "Ephrin-A1 is a negative regulator in glioma through down-regulation of
RT EphA2 and FAK.";
RL Int. J. Oncol. 30:865-871(2007).
RN [12]
RP INTERACTION WITH INPPL1.
RX PubMed=17135240; DOI=10.1074/jbc.m608509200;
RA Zhuang G., Hunter S., Hwang Y., Chen J.;
RT "Regulation of EphA2 receptor endocytosis by SHIP2 lipid phosphatase via
RT phosphatidylinositol 3-Kinase-dependent Rac1 activation.";
RL J. Biol. Chem. 282:2683-2694(2007).
RN [13]
RP FUNCTION IN APOPTOSIS, AND INDUCTION BY UV.
RX PubMed=18339848; DOI=10.1158/0008-5472.can-07-2372;
RA Zhang G., Njauw C.-N., Park J.M., Naruse C., Asano M., Tsao H.;
RT "EphA2 is an essential mediator of UV radiation-induced apoptosis.";
RL Cancer Res. 68:1691-1696(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570; SER-579 AND THR-647, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=18794797; DOI=10.1038/onc.2008.328;
RA Wykosky J., Palma E., Gibo D.M., Ringler S., Turner C.P., Debinski W.;
RT "Soluble monomeric EphrinA1 is released from tumor cells and is a
RT functional ligand for the EphA2 receptor.";
RL Oncogene 27:7260-7273(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570; SER-892 AND SER-901, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP DISEASE, FUNCTION IN CELL MIGRATION, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP ASP-739 AND SER-897, AND PHOSPHORYLATION AT SER-897 BY PKB.
RX PubMed=19573808; DOI=10.1016/j.ccr.2009.04.009;
RA Miao H., Li D.Q., Mukherjee A., Guo H., Petty A., Cutter J., Basilion J.P.,
RA Sedor J., Wu J., Danielpour D., Sloan A.E., Cohen M.L., Wang B.;
RT "EphA2 mediates ligand-dependent inhibition and ligand-independent
RT promotion of cell migration and invasion via a reciprocal regulatory loop
RT with Akt.";
RL Cancer Cell 16:9-20(2009).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-435.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [19]
RP UBIQUITINATION BY STUB1.
RX PubMed=19567782; DOI=10.1158/1541-7786.mcr-08-0582;
RA Annamalai B., Liu X., Gopal U., Isaacs J.S.;
RT "Hsp90 is an essential regulator of EphA2 receptor stability and signaling:
RT implications for cancer cell migration and metastasis.";
RL Mol. Cancer Res. 7:1021-1032(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570; TYR-628; THR-647 AND
RP SER-869, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [21]
RP FUNCTION IN CELL MIGRATION, AND INTERACTION WITH ARHGEF16; DOCK4 AND ELMO2.
RX PubMed=20679435; DOI=10.1083/jcb.201005141;
RA Hiramoto-Yamaki N., Takeuchi S., Ueda S., Harada K., Fujimoto S.,
RA Negishi M., Katoh H.;
RT "Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent
RT mechanism.";
RL J. Cell Biol. 190:461-477(2010).
RN [22]
RP FUNCTION IN KERATINOCYTE ADHESION AND DIFFERENTIATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20861311; DOI=10.1091/mbc.e10-03-0242;
RA Lin S., Gordon K., Kaplan N., Getsios S.;
RT "Ligand targeting of EphA2 enhances keratinocyte adhesion and
RT differentiation via desmoglein 1.";
RL Mol. Biol. Cell 21:3902-3914(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=20223987; DOI=10.1126/science.1181729;
RA Salaita K., Nair P.M., Petit R.S., Neve R.M., Das D., Gray J.W.,
RA Groves J.T.;
RT "Restriction of receptor movement alters cellular response: physical force
RT sensing by EphA2.";
RL Science 327:1380-1385(2010).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=21516087; DOI=10.1038/nm.2341;
RA Lupberger J., Zeisel M.B., Xiao F., Thumann C., Fofana I., Zona L.,
RA Davis C., Mee C.J., Turek M., Gorke S., Royer C., Fischer B., Zahid M.N.,
RA Lavillette D., Fresquet J., Cosset F.L., Rothenberg S.M., Pietschmann T.,
RA Patel A.H., Pessaux P., Doffoel M., Raffelsberger W., Poch O.,
RA McKeating J.A., Brino L., Baumert T.F.;
RT "EGFR and EphA2 are host factors for hepatitis C virus entry and possible
RT targets for antiviral therapy.";
RL Nat. Med. 17:589-595(2011).
RN [27]
RP INTERACTION WITH ANKS1A.
RX PubMed=22332920; DOI=10.1021/bi300141h;
RA Mercurio F.A., Marasco D., Pirone L., Pedone E.M., Pellecchia M., Leone M.;
RT "Solution structure of the first Sam domain of Odin and binding studies
RT with the EphA2 receptor.";
RL Biochemistry 51:2136-2145(2012).
RN [28]
RP INTERACTION WITH HHV-8 GLYCOPROTEIN L/GLYCOPROTEIN H (MICROBIAL INFECTION).
RX PubMed=22635007; DOI=10.1038/nm.2805;
RA Hahn A.S., Kaufmann J.K., Wies E., Naschberger E., Panteleev-Ivlev J.,
RA Schmidt K., Holzer A., Schmidt M., Chen J., Konig S., Ensser A., Myoung J.,
RA Brockmeyer N.H., Sturzl M., Fleckenstein B., Neipel F.;
RT "The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi's
RT sarcoma-associated herpesvirus.";
RL Nat. Med. 18:961-966(2012).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-575; SER-892; SER-897 AND
RP SER-901, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [30]
RP FUNCTION IN CELL MIGRATION, PHOSPHORYLATION AT TYR-930, DEPHOSPHORYLATION
RP AT TYR-930 BY PTPRF, AND INTERACTION WITH NCK1.
RX PubMed=23358419; DOI=10.1128/mcb.01708-12;
RA Lee H., Bennett A.M.;
RT "Receptor protein tyrosine phosphatase-receptor tyrosine kinase substrate
RT screen identifies EphA2 as a target for LAR in cell migration.";
RL Mol. Cell. Biol. 33:1430-1441(2013).
RN [31]
RP INTERACTION WITH CEMIP.
RX PubMed=23936024; DOI=10.1371/journal.pone.0069473;
RA Tiwari A., Schneider M., Fiorino A., Haider R., Okoniewski M.J.,
RA Roschitzki B., Uzozie A., Menigatti M., Jiricny J., Marra G.;
RT "Early insights into the function of KIAA1199, a markedly overexpressed
RT protein in human colorectal tumors.";
RL PLoS ONE 8:E69473-E69473(2013).
RN [32]
RP PHOSPHORYLATION AT SER-897 BY RPS6KA1 AND RPS6KA3, AND FUNCTION IN CELL
RP MIGRATION.
RX PubMed=26158630; DOI=10.1038/ncomms8679;
RA Zhou Y., Yamada N., Tanaka T., Hori T., Yokoyama S., Hayakawa Y., Yano S.,
RA Fukuoka J., Koizumi K., Saiki I., Sakurai H.;
RT "Crucial roles of RSK in cell motility by catalysing serine phosphorylation
RT of EphA2.";
RL Nat. Commun. 6:7679-7679(2015).
RN [33]
RP PHOSPHORYLATION AT SER-897 BY PKA, PHOSPHORYLATION AT SER-901, AND
RP FUNCTION.
RX PubMed=27385333; DOI=10.1091/mbc.e16-01-0048;
RA Barquilla A., Lamberto I., Noberini R., Heynen-Genel S., Brill L.M.,
RA Pasquale E.B.;
RT "Protein kinase A can block EphA2 receptor-mediated cell repulsion by
RT increasing EphA2 S897 phosphorylation.";
RL Mol. Biol. Cell 27:2757-2770(2016).
RN [34]
RP INTERACTION WITH EPSTEIN-BARR VIRUS/HHV-4 GLYCOPROTEIN L/GLYCOPROTEIN H
RP (MICROBIAL INFECTION).
RX PubMed=29292383; DOI=10.1038/s41564-017-0080-8;
RA Zhang H., Li Y., Wang H.B., Zhang A., Chen M.L., Fang Z.X., Dong X.D.,
RA Li S.B., Du Y., Xiong D., He J.Y., Li M.Z., Liu Y.M., Zhou A.J., Zhong Q.,
RA Zeng Y.X., Kieff E., Zhang Z., Gewurz B.E., Zhao B., Zeng M.S.;
RT "Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus
RT entry.";
RL Nat. Microbiol. 3:1-8(2018).
RN [35]
RP INTERACTION WITH EPSTEIN-BARR VIRUS/HHV-4 GLYCOPROTEIN L/GLYCOPROTEIN H
RP (MICROBIAL INFECTION).
RX PubMed=29292384; DOI=10.1038/s41564-017-0081-7;
RA Chen J., Sathiyamoorthy K., Zhang X., Schaller S., Perez White B.E.,
RA Jardetzky T.S., Longnecker R.;
RT "Ephrin receptor A2 is a functional entry receptor for Epstein-Barr
RT virus.";
RL Nat. Microbiol. 3:172-180(2018).
RN [36]
RP INTERACTION WITH TIMD4, AND SUBCELLULAR LOCATION.
RX PubMed=34067457; DOI=10.3390/cells10061290;
RA Moon B., Yang S., Kim K., Lee J., Jeong D., Park D.;
RT "EphA2 Interacts with Tim-4 through Association between Its FN3 Domain and
RT the IgV Domain of Tim-4.";
RL Cells 10:0-0(2021).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 596-900.
RX PubMed=12467573; DOI=10.1016/s0969-2126(02)00907-3;
RA Nowakowski J., Cronin C.N., McRee D.E., Knuth M.W., Nelson C.G.,
RA Pavletich N.P., Rogers J., Sang B.C., Scheibe D.N., Swanson R.V.,
RA Thompson D.A.;
RT "Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases
RT from nanovolume crystallography.";
RL Structure 10:1659-1667(2002).
RN [38]
RP STRUCTURE BY NMR OF 902-976.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the C-terminal SAM-domain of EPHAA2: ephrin type-A
RT receptor 2 precursor (EC 2.7.10.1).";
RL Submitted (JAN-2008) to the PDB data bank.
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 28-201, X-RAY CRYSTALLOGRAPHY
RP (2.0 ANGSTROMS) OF 28-201 IN COMPLEX WITH EFNA1, SUBUNIT, DISULFIDE BOND,
RP AND MUTAGENESIS OF ARG-103.
RX PubMed=19525919; DOI=10.1038/embor.2009.91;
RA Himanen J.P., Goldgur Y., Miao H., Myshkin E., Guo H., Buck M., Nguyen M.,
RA Rajashankar K.R., Wang B., Nikolov D.B.;
RT "Ligand recognition by A-class Eph receptors: crystal structures of the
RT EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex.";
RL EMBO Rep. 10:722-728(2009).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 25-202, AND DISULFIDE BOND.
RG Structural genomics consortium (SGC);
RT "Ephrin A1 bound to the ligand binding domain of the human ephrin A2
RT (EPHA2) receptor protein kinase.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [41]
RP STRUCTURE BY NMR OF 523-563.
RA Mayzel M.L., Bocharov E.V., Volynsky P.E., Arseniev A.S.;
RT "Left-handed dimer of EPHA2 transmembrane domain helix packing diversity
RT among receptor tyrosine kinases.";
RL Submitted (AUG-2009) to the PDB data bank.
RN [42]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 23-202 IN COMPLEX WITH EFNA1, AND
RP SUBUNIT.
RX PubMed=20505120; DOI=10.1073/pnas.1004148107;
RA Himanen J.P., Yermekbayeva L., Janes P.W., Walker J.R., Xu K., Atapattu L.,
RA Rajashankar K.R., Mensinga A., Lackmann M., Nikolov D.B., Dhe-Paganon S.;
RT "Architecture of Eph receptor clusters.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:10860-10865(2010).
RN [43]
RP VARIANTS [LARGE SCALE ANALYSIS] ARG-391; MET-511; HIS-568; SER-777 AND
RP HIS-876.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [44]
RP VARIANT CTRCT6 TRP-948.
RX PubMed=19005574;
RA Shiels A., Bennett T.M., Knopf H.L.S., Maraini G., Li A., Jiao X.,
RA Hejtmancik J.F.;
RT "The EPHA2 gene is associated with cataracts linked to chromosome 1p.";
RL Mol. Vis. 14:2042-2055(2008).
RN [45]
RP VARIANT CTRCT6 ILE-940.
RX PubMed=19306328; DOI=10.1002/humu.20995;
RA Zhang T., Hua R., Xiao W., Burdon K.P., Bhattacharya S.S., Craig J.E.,
RA Shang D., Zhao X., Mackey D.A., Moore A.T., Luo Y., Zhang J., Zhang X.;
RT "Mutations of the EPHA2 receptor tyrosine kinase gene cause autosomal
RT dominant congenital cataract.";
RL Hum. Mutat. 30:E603-E611(2009).
RN [46]
RP VARIANT CTRCT6 GLN-721, AND CHARACTERIZATION OF VARIANT CTRCT6 GLN-721.
RX PubMed=19649315; DOI=10.1371/journal.pgen.1000584;
RA Jun G., Guo H., Klein B.E., Klein R., Wang J.J., Mitchell P., Miao H.,
RA Lee K.E., Joshi T., Buck M., Chugha P., Bardenstein D., Klein A.P.,
RA Bailey-Wilson J.E., Gong X., Spector T.D., Andrew T., Hammond C.J.,
RA Elston R.C., Iyengar S.K., Wang B.;
RT "EPHA2 is associated with age-related cortical cataract in mice and
RT humans.";
RL PLoS Genet. 5:E1000584-E1000584(2009).
RN [47]
RP CHARACTERIZATION OF VARIANTS CTRCT6 ILE-940 AND CTRCT6 TRP-948.
RX PubMed=22570727; DOI=10.1371/journal.pone.0036564;
RA Park J.E., Son A.I., Hua R., Wang L., Zhang X., Zhou R.;
RT "Human cataract mutations in EPHA2 SAM domain alter receptor stability and
RT function.";
RL PLoS ONE 7:E36564-E36564(2012).
CC -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane-
CC bound ephrin-A family ligands residing on adjacent cells, leading to
CC contact-dependent bidirectional signaling into neighboring cells. The
CC signaling pathway downstream of the receptor is referred to as forward
CC signaling while the signaling pathway downstream of the ephrin ligand
CC is referred to as reverse signaling. Activated by the ligand ephrin-
CC A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation
CC and differentiation of cells. Regulates cell adhesion and
CC differentiation through DSG1/desmoglein-1 and inhibition of the
CC ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also
CC participate in UV radiation-induced apoptosis and have a ligand-
CC independent stimulatory effect on chemotactic cell migration. During
CC development, may function in distinctive aspects of pattern formation
CC and subsequently in development of several fetal tissues. Involved for
CC instance in angiogenesis, in early hindbrain development and epithelial
CC proliferation and branching morphogenesis during mammary gland
CC development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens
CC fiber cells shape and interactions and be important for lens
CC transparency development and maintenance. With ephrin-A2/EFNA2 may play
CC a role in bone remodeling through regulation of osteoclastogenesis and
CC osteoblastogenesis. {ECO:0000269|PubMed:10655584,
CC ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848,
CC ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435,
CC ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419,
CC ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C
CC virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV
CC entry by promoting the formation of the CD81-CLDN1 receptor complexes
CC that are essential for HCV entry and by enhancing membrane fusion of
CC cells expressing HCV envelope glycoproteins.
CC {ECO:0000269|PubMed:21516087}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:2174105};
CC -!- SUBUNIT: Homodimer. Interacts with SLA. Interacts (phosphorylated form)
CC with VAV2, VAV3 and PI3-kinase p85 subunit (PIK3R1, PIK3R2 or PIK3R3);
CC critical for the EFNA1-induced activation of RAC1 which stimulates cell
CC migration (By similarity). Interacts with INPPL1; regulates activated
CC EPHA2 endocytosis and degradation. Interacts (inactivated form) with
CC PTK2/FAK1 and interacts (EFNA1 ligand-activated form) with PTPN11;
CC regulates integrin-mediated adhesion. Interacts with ARHGEF16, DOCK4
CC and ELMO2; mediates ligand-independent activation of RAC1 which
CC stimulates cell migration. Interacts with CLDN4; phosphorylates CLDN4
CC and may regulate tight junctions. Interacts with ACP1. Interacts (via
CC SAM domain) with ANKS1A (via SAM domain). Interacts with CEMIP.
CC Interacts with NCK1; may regulate EPHA2 activity in cell migration and
CC adhesion. Interacts with TIMD4 (PubMed:34067457).
CC {ECO:0000250|UniProtKB:Q03145, ECO:0000269|PubMed:10655584,
CC ECO:0000269|PubMed:12167657, ECO:0000269|PubMed:16236711,
CC ECO:0000269|PubMed:17135240, ECO:0000269|PubMed:19525919,
CC ECO:0000269|PubMed:20505120, ECO:0000269|PubMed:20679435,
CC ECO:0000269|PubMed:22332920, ECO:0000269|PubMed:23358419,
CC ECO:0000269|PubMed:23936024, ECO:0000269|PubMed:34067457}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human herpes virus 8/HHV-
CC 8 glycoprotein L/gL and glycoprotein H/gH heterodimer; this interaction
CC triggers EPHA2 phosphorylation and endocytosis, allowing virus entry.
CC {ECO:0000269|PubMed:22635007}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus/HHV-4
CC glycoprotein L/gL and glycoprotein H/gH heterodimer; this interaction
CC facilitates virus internalization and fusion.
CC {ECO:0000269|PubMed:29292383, ECO:0000269|PubMed:29292384}.
CC -!- INTERACTION:
CC P29317; P35222: CTNNB1; NbExp=2; IntAct=EBI-702104, EBI-491549;
CC P29317; P20827: EFNA1; NbExp=9; IntAct=EBI-702104, EBI-715194;
CC P29317; P52803: EFNA5; NbExp=6; IntAct=EBI-702104, EBI-1753674;
CC P29317; Q15375: EPHA7; NbExp=3; IntAct=EBI-702104, EBI-1383428;
CC P29317; P08238: HSP90AB1; NbExp=2; IntAct=EBI-702104, EBI-352572;
CC P29317; O15357-1: INPPL1; NbExp=3; IntAct=EBI-702104, EBI-15963021;
CC P29317; Q05397: PTK2; NbExp=3; IntAct=EBI-702104, EBI-702142;
CC P29317; Q06124: PTPN11; NbExp=2; IntAct=EBI-702104, EBI-297779;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18794797,
CC ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20223987,
CC ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:34067457}; Single-pass
CC type I membrane protein {ECO:0000255}. Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:19573808}; Single-pass type I membrane protein
CC {ECO:0000255}. Cell projection, lamellipodium membrane
CC {ECO:0000269|PubMed:19573808}; Single-pass type I membrane protein
CC {ECO:0000255}. Cell junction, focal adhesion
CC {ECO:0000269|PubMed:10655584}. Note=Present at regions of cell-cell
CC contacts but also at the leading edge of migrating cells
CC (PubMed:19573808, PubMed:20861311). Relocates from the plasma membrane
CC to the cytoplasmic and perinuclear regions in cancer cells
CC (PubMed:18794797). {ECO:0000269|PubMed:18794797,
CC ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20861311,
CC ECO:0000269|PubMed:26158630}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P29317-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P29317-2; Sequence=VSP_056014, VSP_056015;
CC -!- TISSUE SPECIFICITY: Expressed in brain and glioma tissue and glioma
CC cell lines (at protein level). Expressed most highly in tissues that
CC contain a high proportion of epithelial cells, e.g. skin, intestine,
CC lung, and ovary. {ECO:0000269|PubMed:17332925}.
CC -!- INDUCTION: Up-regulated by UV irradiation via a TP53-independent, MAPK-
CC dependent mechanism. {ECO:0000269|PubMed:18339848}.
CC -!- PTM: Autophosphorylates. Phosphorylated on tyrosine upon binding and
CC activation by EFNA1. Phosphorylated residues Tyr-588 and Tyr-594 are
CC required for binding VAV2 and VAV3 while phosphorylated residues Tyr-
CC 735 and Tyr-930 are required for binding PI3-kinase p85 subunit
CC (PIK3R1, PIK3R2 or PIK3R3). These phosphorylated residues are critical
CC for recruitment of VAV2 and VAV3 and PI3-kinase p85 subunit which
CC transduce downstream signaling to activate RAC1 GTPase and cell
CC migration. Dephosphorylation of Tyr-930 by PTPRF prevents the
CC interaction of EPHA2 with NCK1. Phosphorylated at Ser-897 by PKB;
CC serum-induced phosphorylation which targets EPHA2 to the cell leading
CC edge and stimulates cell migration. Phosphorylation by PKB is inhibited
CC by EFNA1-activated EPHA2 which regulates PKB activity via a reciprocal
CC regulatory loop. Phosphorylated at Ser-897 in response to TNF by
CC RPS6KA1 and RPS6KA3; RPS6KA-EPHA2 signaling pathway controls cell
CC migration (PubMed:26158630). Phosphorylated at Ser-897 by PKA; blocks
CC cell retraction induced by EPHA2 kinase activity (PubMed:27385333).
CC Dephosphorylated by ACP1. {ECO:0000269|PubMed:10655584,
CC ECO:0000269|PubMed:18794797, ECO:0000269|PubMed:19573808,
CC ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630,
CC ECO:0000269|PubMed:27385333}.
CC -!- PTM: Ubiquitinated by CHIP/STUB1. Ubiquitination is regulated by the
CC HSP90 chaperone and regulates the receptor stability and activity
CC through proteasomal degradation. ANKS1A prevents ubiquitination and
CC degradation (By similarity). {ECO:0000250}.
CC -!- DISEASE: Cataract 6, multiple types (CTRCT6) [MIM:116600]: An
CC opacification of the crystalline lens of the eye that frequently
CC results in visual impairment or blindness. Opacities vary in
CC morphology, are often confined to a portion of the lens, and may be
CC static or progressive. CTRCT6 includes posterior polar and age-related
CC cortical cataracts, among others. Posterior polar cataract is a
CC subcapsular opacity, usually disk-shaped, located at the back of the
CC lens. Age-related cortical cataract is a developmental punctate opacity
CC restricted to the cortex. The cataract is white or cerulean, increases
CC in number with age, but rarely affects vision.
CC {ECO:0000269|PubMed:19005574, ECO:0000269|PubMed:19306328,
CC ECO:0000269|PubMed:19649315, ECO:0000269|PubMed:22570727}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=Overexpressed in several cancer types and promotes
CC malignancy. {ECO:0000269|PubMed:19573808}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/EPHA2ID40462ch1p36.html";
CC ---------------------------------------------------------------------------
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DR EMBL; M59371; AAA53375.1; -; mRNA.
DR EMBL; EU826606; ACF47642.1; -; mRNA.
DR EMBL; AL451042; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471167; EAW51769.1; -; Genomic_DNA.
DR EMBL; BC037166; AAH37166.1; -; mRNA.
DR CCDS; CCDS169.1; -. [P29317-1]
DR PIR; A36355; A36355.
DR RefSeq; NP_004422.2; NM_004431.4. [P29317-1]
DR PDB; 1MQB; X-ray; 2.30 A; A/B=596-900.
DR PDB; 2E8N; NMR; -; A=902-976.
DR PDB; 2K9Y; NMR; -; A/B=523-563.
DR PDB; 2KSO; NMR; -; A=908-972.
DR PDB; 2X10; X-ray; 3.00 A; A=27-534.
DR PDB; 2X11; X-ray; 4.83 A; A=27-534.
DR PDB; 3C8X; X-ray; 1.95 A; A=23-202.
DR PDB; 3CZU; X-ray; 2.65 A; A=23-202.
DR PDB; 3FL7; X-ray; 2.50 A; A=23-531.
DR PDB; 3HEI; X-ray; 2.00 A; A/C/E/G/I/K/M/O=28-201.
DR PDB; 3HPN; X-ray; 2.52 A; A/B/C/D/E/F=28-201.
DR PDB; 3KKA; X-ray; 2.40 A; C/D/E=903-971.
DR PDB; 3MBW; X-ray; 2.81 A; A=23-326.
DR PDB; 3MX0; X-ray; 3.51 A; A/C=27-435.
DR PDB; 3SKJ; X-ray; 2.50 A; E/F=23-202.
DR PDB; 4P2K; X-ray; 1.50 A; A=590-876.
DR PDB; 4PDO; X-ray; 2.10 A; A/B=590-876.
DR PDB; 4TRL; X-ray; 2.45 A; A=590-876.
DR PDB; 5EK7; X-ray; 1.90 A; A/B=583-876.
DR PDB; 5I9U; X-ray; 1.89 A; A=596-900.
DR PDB; 5I9V; X-ray; 1.46 A; A=596-900.
DR PDB; 5I9W; X-ray; 1.36 A; A=596-900.
DR PDB; 5I9X; X-ray; 1.43 A; A=596-900.
DR PDB; 5I9Y; X-ray; 1.23 A; A=596-900.
DR PDB; 5I9Z; X-ray; 1.70 A; A=596-900.
DR PDB; 5IA0; X-ray; 1.95 A; A/B/C=596-900.
DR PDB; 5IA1; X-ray; 2.04 A; A=596-900.
DR PDB; 5IA2; X-ray; 1.62 A; A=596-900.
DR PDB; 5IA3; X-ray; 1.79 A; A=596-900.
DR PDB; 5IA4; X-ray; 1.80 A; A=596-900.
DR PDB; 5IA5; X-ray; 1.78 A; A=596-900.
DR PDB; 5NJZ; X-ray; 1.77 A; A=596-900.
DR PDB; 5NK0; X-ray; 1.60 A; A=596-900.
DR PDB; 5NK1; X-ray; 1.55 A; A=596-900.
DR PDB; 5NK2; X-ray; 1.65 A; A=596-900.
DR PDB; 5NK3; X-ray; 1.59 A; A=596-900.
DR PDB; 5NK4; X-ray; 1.45 A; A=596-900.
DR PDB; 5NK5; X-ray; 1.33 A; A=596-900.
DR PDB; 5NK6; X-ray; 1.27 A; A=596-900.
DR PDB; 5NK7; X-ray; 1.89 A; A=596-900.
DR PDB; 5NK8; X-ray; 1.76 A; A=596-900.
DR PDB; 5NK9; X-ray; 1.59 A; A=596-900.
DR PDB; 5NKA; X-ray; 1.38 A; A=596-900.
DR PDB; 5NKB; X-ray; 1.50 A; A=596-900.
DR PDB; 5NKC; X-ray; 1.45 A; A=596-900.
DR PDB; 5NKD; X-ray; 1.41 A; A=596-900.
DR PDB; 5NKE; X-ray; 1.39 A; A=596-900.
DR PDB; 5NKF; X-ray; 1.10 A; A=596-900.
DR PDB; 5NKG; X-ray; 1.10 A; A=596-900.
DR PDB; 5NKH; X-ray; 1.29 A; A=596-900.
DR PDB; 5NKI; X-ray; 1.68 A; A=596-900.
DR PDB; 5NZ9; NMR; -; A=945-969.
DR PDB; 6B9L; X-ray; 3.20 A; A/B/C/D=27-200.
DR PDB; 6F7M; NMR; -; A=945-969.
DR PDB; 6F7N; NMR; -; A=951-963.
DR PDB; 6FNF; X-ray; 1.56 A; A=596-900.
DR PDB; 6FNG; X-ray; 1.04 A; A=596-900.
DR PDB; 6FNH; X-ray; 1.38 A; A/B/C=596-900.
DR PDB; 6HES; X-ray; 1.13 A; A=596-900.
DR PDB; 6HET; X-ray; 1.21 A; A=596-900.
DR PDB; 6HEU; X-ray; 1.72 A; A=596-900.
DR PDB; 6HEV; X-ray; 1.28 A; A=596-900.
DR PDB; 6HEW; X-ray; 1.27 A; A=596-900.
DR PDB; 6HEX; X-ray; 1.41 A; A=596-900.
DR PDB; 6HEY; X-ray; 1.37 A; A=596-900.
DR PDB; 6NJZ; X-ray; 1.90 A; A/B=28-200.
DR PDB; 6NK0; X-ray; 1.53 A; A/B=28-200.
DR PDB; 6NK1; X-ray; 1.55 A; A/B=28-200.
DR PDB; 6NK2; X-ray; 2.20 A; A/B=28-200.
DR PDB; 6NKP; X-ray; 2.03 A; A/B=28-200.
DR PDB; 6Q7B; X-ray; 1.01 A; A=596-900.
DR PDB; 6Q7C; X-ray; 1.05 A; A=596-900.
DR PDB; 6Q7D; X-ray; 0.98 A; A=596-900.
DR PDB; 6Q7E; X-ray; 1.06 A; A=596-900.
DR PDB; 6Q7F; X-ray; 1.20 A; A=596-900.
DR PDB; 6Q7G; X-ray; 1.05 A; A=596-900.
DR PDB; 6RW2; X-ray; 2.26 A; A=27-201.
DR PDB; 7B7N; X-ray; 2.69 A; E=23-202.
DR PDB; 7CZE; X-ray; 3.00 A; I/J/K/L=26-200.
DR PDB; 7CZF; X-ray; 3.20 A; A/D=28-206.
DR PDB; 7KJA; X-ray; 1.75 A; A/B=590-976.
DR PDB; 7KJB; X-ray; 2.80 A; A=590-976.
DR PDB; 7KJC; X-ray; 2.30 A; A/B=590-976.
DR PDBsum; 1MQB; -.
DR PDBsum; 2E8N; -.
DR PDBsum; 2K9Y; -.
DR PDBsum; 2KSO; -.
DR PDBsum; 2X10; -.
DR PDBsum; 2X11; -.
DR PDBsum; 3C8X; -.
DR PDBsum; 3CZU; -.
DR PDBsum; 3FL7; -.
DR PDBsum; 3HEI; -.
DR PDBsum; 3HPN; -.
DR PDBsum; 3KKA; -.
DR PDBsum; 3MBW; -.
DR PDBsum; 3MX0; -.
DR PDBsum; 3SKJ; -.
DR PDBsum; 4P2K; -.
DR PDBsum; 4PDO; -.
DR PDBsum; 4TRL; -.
DR PDBsum; 5EK7; -.
DR PDBsum; 5I9U; -.
DR PDBsum; 5I9V; -.
DR PDBsum; 5I9W; -.
DR PDBsum; 5I9X; -.
DR PDBsum; 5I9Y; -.
DR PDBsum; 5I9Z; -.
DR PDBsum; 5IA0; -.
DR PDBsum; 5IA1; -.
DR PDBsum; 5IA2; -.
DR PDBsum; 5IA3; -.
DR PDBsum; 5IA4; -.
DR PDBsum; 5IA5; -.
DR PDBsum; 5NJZ; -.
DR PDBsum; 5NK0; -.
DR PDBsum; 5NK1; -.
DR PDBsum; 5NK2; -.
DR PDBsum; 5NK3; -.
DR PDBsum; 5NK4; -.
DR PDBsum; 5NK5; -.
DR PDBsum; 5NK6; -.
DR PDBsum; 5NK7; -.
DR PDBsum; 5NK8; -.
DR PDBsum; 5NK9; -.
DR PDBsum; 5NKA; -.
DR PDBsum; 5NKB; -.
DR PDBsum; 5NKC; -.
DR PDBsum; 5NKD; -.
DR PDBsum; 5NKE; -.
DR PDBsum; 5NKF; -.
DR PDBsum; 5NKG; -.
DR PDBsum; 5NKH; -.
DR PDBsum; 5NKI; -.
DR PDBsum; 5NZ9; -.
DR PDBsum; 6B9L; -.
DR PDBsum; 6F7M; -.
DR PDBsum; 6F7N; -.
DR PDBsum; 6FNF; -.
DR PDBsum; 6FNG; -.
DR PDBsum; 6FNH; -.
DR PDBsum; 6HES; -.
DR PDBsum; 6HET; -.
DR PDBsum; 6HEU; -.
DR PDBsum; 6HEV; -.
DR PDBsum; 6HEW; -.
DR PDBsum; 6HEX; -.
DR PDBsum; 6HEY; -.
DR PDBsum; 6NJZ; -.
DR PDBsum; 6NK0; -.
DR PDBsum; 6NK1; -.
DR PDBsum; 6NK2; -.
DR PDBsum; 6NKP; -.
DR PDBsum; 6Q7B; -.
DR PDBsum; 6Q7C; -.
DR PDBsum; 6Q7D; -.
DR PDBsum; 6Q7E; -.
DR PDBsum; 6Q7F; -.
DR PDBsum; 6Q7G; -.
DR PDBsum; 6RW2; -.
DR PDBsum; 7B7N; -.
DR PDBsum; 7CZE; -.
DR PDBsum; 7CZF; -.
DR PDBsum; 7KJA; -.
DR PDBsum; 7KJB; -.
DR PDBsum; 7KJC; -.
DR AlphaFoldDB; P29317; -.
DR BMRB; P29317; -.
DR SMR; P29317; -.
DR BioGRID; 108288; 263.
DR CORUM; P29317; -.
DR DIP; DIP-96N; -.
DR IntAct; P29317; 91.
DR MINT; P29317; -.
DR STRING; 9606.ENSP00000351209; -.
DR BindingDB; P29317; -.
DR ChEMBL; CHEMBL2068; -.
DR DrugBank; DB01254; Dasatinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester.
DR DrugBank; DB08896; Regorafenib.
DR DrugCentral; P29317; -.
DR GuidetoPHARMACOLOGY; 1822; -.
DR GlyConnect; 777; 3 N-Linked glycans (1 site).
DR GlyGen; P29317; 2 sites, 4 N-linked glycans (1 site).
DR iPTMnet; P29317; -.
DR PhosphoSitePlus; P29317; -.
DR SwissPalm; P29317; -.
DR BioMuta; EPHA2; -.
DR DMDM; 229462861; -.
DR CPTAC; CPTAC-1784; -.
DR CPTAC; CPTAC-2783; -.
DR EPD; P29317; -.
DR jPOST; P29317; -.
DR MassIVE; P29317; -.
DR MaxQB; P29317; -.
DR PaxDb; P29317; -.
DR PeptideAtlas; P29317; -.
DR PRIDE; P29317; -.
DR ProteomicsDB; 54535; -. [P29317-1]
DR ABCD; P29317; 26 sequenced antibodies.
DR Antibodypedia; 4183; 1285 antibodies from 46 providers.
DR DNASU; 1969; -.
DR Ensembl; ENST00000358432.8; ENSP00000351209.5; ENSG00000142627.13. [P29317-1]
DR GeneID; 1969; -.
DR KEGG; hsa:1969; -.
DR MANE-Select; ENST00000358432.8; ENSP00000351209.5; NM_004431.5; NP_004422.2.
DR UCSC; uc001aya.2; human. [P29317-1]
DR CTD; 1969; -.
DR DisGeNET; 1969; -.
DR GeneCards; EPHA2; -.
DR HGNC; HGNC:3386; EPHA2.
DR HPA; ENSG00000142627; Tissue enhanced (esophagus).
DR MalaCards; EPHA2; -.
DR MIM; 116600; phenotype.
DR MIM; 176946; gene.
DR neXtProt; NX_P29317; -.
DR OpenTargets; ENSG00000142627; -.
DR Orphanet; 98991; Early-onset nuclear cataract.
DR Orphanet; 98993; Early-onset posterior polar cataract.
DR Orphanet; 441447; Early-onset posterior subcapsular cataract.
DR Orphanet; 98994; Total early-onset cataract.
DR PharmGKB; PA27818; -.
DR VEuPathDB; HostDB:ENSG00000142627; -.
DR eggNOG; KOG0196; Eukaryota.
DR GeneTree; ENSGT00940000160786; -.
DR HOGENOM; CLU_000288_141_4_1; -.
DR InParanoid; P29317; -.
DR OMA; MPIYMYT; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; P29317; -.
DR TreeFam; TF315608; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P29317; -.
DR Reactome; R-HSA-2682334; EPH-Ephrin signaling.
DR Reactome; R-HSA-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9013424; RHOV GTPase cycle.
DR Reactome; R-HSA-9696264; RND3 GTPase cycle.
DR Reactome; R-HSA-9696270; RND2 GTPase cycle.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
DR SignaLink; P29317; -.
DR SIGNOR; P29317; -.
DR BioGRID-ORCS; 1969; 13 hits in 1116 CRISPR screens.
DR ChiTaRS; EPHA2; human.
DR EvolutionaryTrace; P29317; -.
DR GeneWiki; EPH_receptor_A2; -.
DR GenomeRNAi; 1969; -.
DR Pharos; P29317; Tclin.
DR PRO; PR:P29317; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P29317; protein.
DR Bgee; ENSG00000142627; Expressed in lower esophagus mucosa and 141 other tissues.
DR ExpressionAtlas; P29317; baseline and differential.
DR Genevisible; P29317; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031256; C:leading edge membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070160; C:tight junction; IDA:ARUK-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0019838; F:growth factor binding; IPI:ARUK-UCL.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IBA:GO_Central.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0090630; P:activation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0048320; P:axial mesoderm formation; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IEA:Ensembl.
DR GO; GO:0046849; P:bone remodeling; ISS:UniProtKB.
DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; ISS:UniProtKB.
DR GO; GO:0046058; P:cAMP metabolic process; IMP:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0060326; P:cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0048870; P:cell motility; IMP:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0070309; P:lens fiber cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0032682; P:negative regulation of chemokine production; IEA:Ensembl.
DR GO; GO:1901491; P:negative regulation of lymphangiogenesis; IEA:Ensembl.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0021915; P:neural tube development; IEA:Ensembl.
DR GO; GO:0060035; P:notochord cell development; IEA:Ensembl.
DR GO; GO:0014028; P:notochord formation; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0030316; P:osteoclast differentiation; ISS:UniProtKB.
DR GO; GO:1904238; P:pericyte cell differentiation; IEA:Ensembl.
DR GO; GO:1903348; P:positive regulation of bicellular tight junction assembly; IMP:ARUK-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:ARUK-UCL.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl.
DR GO; GO:0043491; P:protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:ARUK-UCL.
DR GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0043535; P:regulation of blood vessel endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IDA:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0010591; P:regulation of lamellipodium assembly; IMP:UniProtKB.
DR GO; GO:0070848; P:response to growth factor; IMP:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
DR CDD; cd10480; EphR_LBD_A2; 1.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR034263; EphA2_rcpt_lig-bd.
DR InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016257; Tyr_kinase_ephrin_rcpt.
DR InterPro; IPR001426; Tyr_kinase_rcpt_V_CS.
DR Pfam; PF14575; EphA2_TM; 1.
DR Pfam; PF01404; Ephrin_lbd; 1.
DR Pfam; PF00041; fn3; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00536; SAM_1; 1.
DR PIRSF; PIRSF000666; TyrPK_ephrin_receptor; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00615; EPH_lbd; 1.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS51550; EPH_LBD; 1.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00790; RECEPTOR_TYR_KIN_V_1; 1.
DR PROSITE; PS00791; RECEPTOR_TYR_KIN_V_2; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Angiogenesis; Apoptosis; ATP-binding;
KW Cataract; Cell adhesion; Cell junction; Cell membrane; Cell projection;
KW Differentiation; Disease variant; Disulfide bond; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome;
KW Repeat; Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..976
FT /note="Ephrin type-A receptor 2"
FT /id="PRO_0000016800"
FT TOPO_DOM 24..537
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 538..558
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 559..976
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..206
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 328..432
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 438..529
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 613..875
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 904..968
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..206
FT /note="Mediates interaction with CLDN4"
FT /evidence="ECO:0000269|PubMed:16236711"
FT REGION 606..906
FT /note="Mediates interaction with ARHGEF16 and ELMO2"
FT /evidence="ECO:0000269|PubMed:20679435"
FT REGION 886..976
FT /note="Negatively regulates interaction with ARHGEF16"
FT /evidence="ECO:0000269|PubMed:20679435"
FT MOTIF 974..976
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 739
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 619..627
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 646
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 570
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195"
FT MOD_RES 575
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 588
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 594
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q03145"
FT MOD_RES 628
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 647
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 735
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q03145"
FT MOD_RES 772
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q03145"
FT MOD_RES 869
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 892
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 897
FT /note="Phosphoserine; by PKB/AKT1, RPS6KA1, RPS6KA3 AND
FT PKA"
FT /evidence="ECO:0000269|PubMed:19573808,
FT ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 901
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27385333,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 921
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 930
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:23358419"
FT CARBOHYD 407
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT DISULFID 70..188
FT DISULFID 105..115
FT VAR_SEQ 477..497
FT /note="GDSNSYNVRRTEGFSVTLDDL -> VTPRGAGLALAGPTAGDRLVT (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_056014"
FT VAR_SEQ 498..976
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_056015"
FT VARIANT 99
FT /note="K -> N (in dbSNP:rs1058372)"
FT /id="VAR_055989"
FT VARIANT 391
FT /note="G -> R (in dbSNP:rs34192549)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042121"
FT VARIANT 511
FT /note="T -> M (in dbSNP:rs55747232)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042122"
FT VARIANT 568
FT /note="R -> H (in dbSNP:rs56198600)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042123"
FT VARIANT 631
FT /note="M -> T (in dbSNP:rs34021505)"
FT /id="VAR_055990"
FT VARIANT 721
FT /note="R -> Q (in CTRCT6; retained in the cytoplasm and
FT constitutively active it alters EPHA2 signaling;
FT dbSNP:rs116506614)"
FT /evidence="ECO:0000269|PubMed:19649315"
FT /id="VAR_062532"
FT VARIANT 777
FT /note="G -> S (in a gastric adenocarcinoma sample; somatic
FT mutation; dbSNP:rs922655349)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042124"
FT VARIANT 876
FT /note="R -> H (in dbSNP:rs35903225)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042125"
FT VARIANT 940
FT /note="T -> I (in CTRCT6; reduced protein stability and
FT reduced ability to stimulate cell migration in absence of
FT its ephrin ligand; dbSNP:rs137853200)"
FT /evidence="ECO:0000269|PubMed:19306328,
FT ECO:0000269|PubMed:22570727"
FT /id="VAR_058907"
FT VARIANT 948
FT /note="G -> W (in CTRCT6; reduced protein stability and
FT reduced ability to stimulate cell migration in absence of
FT its ephrin ligand; dbSNP:rs137853199)"
FT /evidence="ECO:0000269|PubMed:19005574,
FT ECO:0000269|PubMed:22570727"
FT /id="VAR_058908"
FT MUTAGEN 103
FT /note="R->E: Significantly reduced response to EFNA1."
FT /evidence="ECO:0000269|PubMed:19525919"
FT MUTAGEN 646
FT /note="K->M: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:16236711"
FT MUTAGEN 739
FT /note="D->N: Increases serum-induced chemotaxis. Loss of
FT EFNA1-dependent regulation of cell migration."
FT /evidence="ECO:0000269|PubMed:19573808"
FT MUTAGEN 897
FT /note="S->A,D: Loss of serum-induced phosphorylation by
FT PKB. Loss of serum-induced chemotaxis."
FT /evidence="ECO:0000269|PubMed:19573808"
FT CONFLICT 94..99
FT /note="IFIELK -> NNFELN (in Ref. 1; AAA53375)"
FT /evidence="ECO:0000305"
FT STRAND 28..33
FT /evidence="ECO:0007829|PDB:6NK0"
FT HELIX 34..37
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:6NK0"
FT TURN 48..50
FT /evidence="ECO:0007829|PDB:6NK1"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 92..103
FT /evidence="ECO:0007829|PDB:6NK0"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:3HEI"
FT TURN 112..114
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 119..128
FT /evidence="ECO:0007829|PDB:6NK0"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:6RW2"
FT HELIX 153..157
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 175..199
FT /evidence="ECO:0007829|PDB:6NK0"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:3MBW"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:3MBW"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:3MBW"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 272..275
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:3MBW"
FT STRAND 295..298
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 335..338
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 343..348
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 361..369
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 384..387
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 389..392
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 394..400
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 407..415
FT /evidence="ECO:0007829|PDB:3FL7"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 427..433
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 441..446
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 453..457
FT /evidence="ECO:0007829|PDB:3FL7"
FT TURN 460..465
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 467..475
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 483..493
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 502..510
FT /evidence="ECO:0007829|PDB:3FL7"
FT STRAND 522..525
FT /evidence="ECO:0007829|PDB:3FL7"
FT HELIX 536..556
FT /evidence="ECO:0007829|PDB:2K9Y"
FT STRAND 557..561
FT /evidence="ECO:0007829|PDB:2K9Y"
FT HELIX 591..594
FT /evidence="ECO:0007829|PDB:5EK7"
FT HELIX 597..600
FT /evidence="ECO:0007829|PDB:4PDO"
FT TURN 601..604
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 610..612
FT /evidence="ECO:0007829|PDB:6Q7D"
FT STRAND 613..622
FT /evidence="ECO:0007829|PDB:6Q7D"
FT STRAND 625..632
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 635..637
FT /evidence="ECO:0007829|PDB:5NKH"
FT STRAND 641..648
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 654..669
FT /evidence="ECO:0007829|PDB:6Q7D"
FT STRAND 678..682
FT /evidence="ECO:0007829|PDB:6Q7D"
FT STRAND 684..693
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 700..706
FT /evidence="ECO:0007829|PDB:6Q7D"
FT TURN 707..709
FT /evidence="ECO:0007829|PDB:6Q7E"
FT HELIX 713..732
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 742..744
FT /evidence="ECO:0007829|PDB:6Q7D"
FT STRAND 745..747
FT /evidence="ECO:0007829|PDB:6Q7D"
FT STRAND 753..755
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 762..766
FT /evidence="ECO:0007829|PDB:5NKF"
FT STRAND 770..772
FT /evidence="ECO:0007829|PDB:5NKF"
FT STRAND 776..778
FT /evidence="ECO:0007829|PDB:5NKH"
FT HELIX 781..783
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 786..791
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 796..811
FT /evidence="ECO:0007829|PDB:6Q7D"
FT TURN 817..820
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 823..831
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 844..853
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 858..860
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 864..876
FT /evidence="ECO:0007829|PDB:6Q7D"
FT HELIX 878..881
FT /evidence="ECO:0007829|PDB:6Q7D"
FT STRAND 882..884
FT /evidence="ECO:0007829|PDB:6Q7D"
FT STRAND 892..894
FT /evidence="ECO:0007829|PDB:7KJB"
FT HELIX 909..915
FT /evidence="ECO:0007829|PDB:7KJA"
FT HELIX 919..921
FT /evidence="ECO:0007829|PDB:7KJA"
FT HELIX 922..927
FT /evidence="ECO:0007829|PDB:7KJA"
FT HELIX 933..936
FT /evidence="ECO:0007829|PDB:7KJA"
FT HELIX 941..946
FT /evidence="ECO:0007829|PDB:7KJA"
FT HELIX 952..969
FT /evidence="ECO:0007829|PDB:7KJA"
SQ SEQUENCE 976 AA; 108266 MW; 845D7E1BBCCAACCC CRC64;
MELQAARACF ALLWGCALAA AAAAQGKEVV LLDFAAAGGE LGWLTHPYGK GWDLMQNIMN
DMPIYMYSVC NVMSGDQDNW LRTNWVYRGE AERIFIELKF TVRDCNSFPG GASSCKETFN
LYYAESDLDY GTNFQKRLFT KIDTIAPDEI TVSSDFEARH VKLNVEERSV GPLTRKGFYL
AFQDIGACVA LLSVRVYYKK CPELLQGLAH FPETIAGSDA PSLATVAGTC VDHAVVPPGG
EEPRMHCAVD GEWLVPIGQC LCQAGYEKVE DACQACSPGF FKFEASESPC LECPEHTLPS
PEGATSCECE EGFFRAPQDP ASMPCTRPPS APHYLTAVGM GAKVELRWTP PQDSGGREDI
VYSVTCEQCW PESGECGPCE ASVRYSEPPH GLTRTSVTVS DLEPHMNYTF TVEARNGVSG
LVTSRSFRTA SVSINQTEPP KVRLEGRSTT SLSVSWSIPP PQQSRVWKYE VTYRKKGDSN
SYNVRRTEGF SVTLDDLAPD TTYLVQVQAL TQEGQGAGSK VHEFQTLSPE GSGNLAVIGG
VAVGVVLLLV LAGVGFFIHR RRKNQRARQS PEDVYFSKSE QLKPLKTYVD PHTYEDPNQA
VLKFTTEIHP SCVTRQKVIG AGEFGEVYKG MLKTSSGKKE VPVAIKTLKA GYTEKQRVDF
LGEAGIMGQF SHHNIIRLEG VISKYKPMMI ITEYMENGAL DKFLREKDGE FSVLQLVGML
RGIAAGMKYL ANMNYVHRDL AARNILVNSN LVCKVSDFGL SRVLEDDPEA TYTTSGGKIP
IRWTAPEAIS YRKFTSASDV WSFGIVMWEV MTYGERPYWE LSNHEVMKAI NDGFRLPTPM
DCPSAIYQLM MQCWQQERAR RPKFADIVSI LDKLIRAPDS LKTLADFDPR VSIRLPSTSG
SEGVPFRTVS EWLESIKMQQ YTEHFMAAGY TAIEKVVQMT NDDIKRIGVR LPGHQKRIAY
SLLGLKDQVN TVGIPI
