EPHB4_HUMAN
ID EPHB4_HUMAN Reviewed; 987 AA.
AC P54760; B5A970; B5A971; B5A972; Q7Z635; Q9BTA5; Q9BXP0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 18-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Ephrin type-B receptor 4;
DE EC=2.7.10.1;
DE AltName: Full=Hepatoma transmembrane kinase;
DE AltName: Full=Tyrosine-protein kinase TYRO11;
DE Flags: Precursor;
GN Name=EPHB4; Synonyms=HTK, MYK1, TYRO11;
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), SUBCELLULAR LOCATION,
RP AUTOPHOSPHORYLATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=8188704; DOI=10.1016/s0021-9258(17)36776-5;
RA Bennett B.D., Wang Z., Kuang W.J., Wang A., Groopman J.E., Goeddel D.V.,
RA Scadden D.T.;
RT "Cloning and characterization of HTK, a novel transmembrane tyrosine kinase
RT of the EPH subfamily.";
RL J. Biol. Chem. 269:14211-14218(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11239002; DOI=10.1093/nar/29.6.1352;
RA Wilson M.D., Riemer C., Martindale D.W., Schnupf P., Boright A.P.,
RA Cheung T.L., Hardy D.M., Schwartz S., Scherer S.W., Tsui L.-C., Miller W.,
RA Koop B.F.;
RT "Comparative analysis of the gene-dense ACHE/TFR2 region on human
RT chromosome 7q22 with the orthologous region on mouse chromosome 5.";
RL Nucleic Acids Res. 29:1352-1365(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-162.
RC TISSUE=Ovary, and 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 [5]
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 [6]
RP FUNCTION IN ANGIOGENESIS, FUNCTION IN CELL ADHESION, AND FUNCTION IN CELL
RP MIGRATION.
RX PubMed=12734395; DOI=10.1242/jcs.00426;
RA Fueller T., Korff T., Kilian A., Dandekar G., Augustin H.G.;
RT "Forward EphB4 signaling in endothelial cells controls cellular repulsion
RT and segregation from ephrinB2 positive cells.";
RL J. Cell Sci. 116:2461-2470(2003).
RN [7]
RP FUNCTION IN ANGIOGENESIS.
RX PubMed=16424904; DOI=10.1038/sj.emboj.7600949;
RA Erber R., Eichelsbacher U., Powajbo V., Korn T., Djonov V., Lin J.,
RA Hammes H.P., Grobholz R., Ullrich A., Vajkoczy P.;
RT "EphB4 controls blood vascular morphogenesis during postnatal
RT angiogenesis.";
RL EMBO J. 25:628-641(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-911 AND THR-976, 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-976, AND IDENTIFICATION BY
RP 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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-911; THR-976 AND TYR-987, AND
RP 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 [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-769; SER-770 AND THR-976, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-943, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 17-196 IN COMPLEX WITH EFNB2,
RP MUTAGENESIS OF LEU-95, AND DISULFIDE BOND.
RX PubMed=16867992; DOI=10.1074/jbc.m605766200;
RA Chrencik J.E., Brooun A., Kraus M.L., Recht M.I., Kolatkar A.R., Han G.W.,
RA Seifert J.M., Widmer H., Auer M., Kuhn P.;
RT "Structural and biophysical characterization of the EphB4*ephrinB2 protein-
RT protein interaction and receptor specificity.";
RL J. Biol. Chem. 281:28185-28192(2006).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 17-196 IN COMPLEX WITH
RP ANTAGONISTIC PEPTIDE, AND DISULFIDE BOND.
RX PubMed=16472751; DOI=10.1016/j.str.2005.11.011;
RA Chrencik J.E., Brooun A., Recht M.I., Kraus M.L., Koolpe M., Kolatkar A.R.,
RA Bruce R.H., Martiny-Baron G., Widmer H., Pasquale E.B., Kuhn P.;
RT "Structure and thermodynamic characterization of the EphB4/Ephrin-B2
RT antagonist peptide complex reveals the determinants for receptor
RT specificity.";
RL Structure 14:321-330(2006).
RN [17]
RP STRUCTURE BY NMR OF 434-529.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the second FN3 domain from human ephrin type-B
RT receptor 4.";
RL Submitted (JUL-2007) to the PDB data bank.
RN [18]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-67; ILE-113; LEU-346; VAL-371; GLU-576;
RP HIS-678; THR-882; TRP-889 AND ASP-890.
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 [19]
RP INVOLVEMENT IN LMPHM7, VARIANTS LMPHM7 GLN-739 AND SER-782,
RP CHARACTERIZATION OF VARIANTS LMPHM7 GLU-739 AND SER-782, AND FUNCTION.
RX PubMed=27400125; DOI=10.1172/jci85794;
RA Martin-Almedina S., Martinez-Corral I., Holdhus R., Vicente A., Fotiou E.,
RA Lin S., Petersen K., Simpson M.A., Hoischen A., Gilissen C., Jeffery H.,
RA Atton G., Karapouliou C., Brice G., Gordon K., Wiseman J.W., Wedin M.,
RA Rockson S.G., Jeffery S., Mortimer P.S., Snyder M.P., Berland S.,
RA Mansour S., Makinen T., Ostergaard P.;
RT "EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-
RT related hydrops fetalis.";
RL J. Clin. Invest. 126:3080-3088(2016).
RN [20]
RP VARIANTS CMAVM2 LYS-59; PRO-74; TYR-115 DEL; 130-TRP--TYR-987 DEL;
RP 161-VAL-LYS-162 DELINS LEU; PRO-187; 244-GLN--TYR-987 DEL; ARG-268;
RP 352-ARG--TYR-987 DEL; 375-GLY--TYR-987 DEL; 431-ARG--TYR-987 DEL; GLY-469;
RP ARG-516; 520-GLN--TYR-987 DEL; 596-TYR--TYR-987 DEL; TRP-656; LYS-664;
RP THR-725; 739-ARG--TYR-987 DEL; ASP-745; ARG-789; SER-789; 806-TYR--TYR-987
RP DEL; ARG-807; LEU-820; THR-820; TRP-838; ARG-845; TYR-856; TRP-864 AND
RP PRO-874, CHARACTERIZATION OF VARIANTS CMAVM2 LYS-664; TRP-838; ARG-845 AND
RP TRP-864, INVOLVEMENT IN CMAVM2, AND SUBCELLULAR LOCATION.
RX PubMed=28687708; DOI=10.1161/circulationaha.116.026886;
RA Amyere M., Revencu N., Helaers R., Pairet E., Baselga E., Cordisco M.,
RA Chung W., Dubois J., Lacour J.P., Martorell L., Mazereeuw-Hautier J.,
RA Pyeritz R.E., Amor D.J., Bisdorff A., Blei F., Bombei H., Dompmartin A.,
RA Brooks D., Dupont J., Gonzalez-Ensenat M.A., Frieden I., Gerard M.,
RA Kvarnung M., Hanson-Kahn A.K., Hudgins L., Leaute-Labreze C., McCuaig C.,
RA Metry D., Parent P., Paul C., Petit F., Phan A., Quere I., Salhi A.,
RA Turner A., Vabres P., Vicente A., Wargon O., Watanabe S., Weibel L.,
RA Wilson A., Willing M., Mulliken J.B., Boon L.M., Vikkula M.;
RT "Germline loss-of-function mutations in EPHB4 cause a second form of
RT capillary malformation-arteriovenous malformation (CM-AVM2) deregulating
RT RAS-MAPK signaling.";
RL Circulation 136:1037-1048(2017).
RN [21]
RP VARIANT CMAVM2 GLY-802, AND INVOLVEMENT IN CMAVM2.
RX PubMed=28730721; DOI=10.1111/pde.13208;
RA Yu J., Streicher J.L., Medne L., Krantz I.D., Yan A.C.;
RT "EPHB4 mutation implicated in capillary malformation-arteriovenous
RT malformation syndrome: A case report.";
RL Pediatr. Dermatol. 34:E227-E230(2017).
RN [22]
RP VARIANTS CMAVM2 ARG-107 AND GLU-870, AND INVOLVEMENT IN CMAVM2.
RX PubMed=29444212; DOI=10.1093/brain/awy020;
RA Vivanti A., Ozanne A., Grondin C., Saliou G., Quevarec L., Maurey H.,
RA Aubourg P., Benachi A., Gut M., Gut I., Martinovic J., Senat M.V., Tawk M.,
RA Melki J.;
RT "Loss of function mutations in EPHB4 are responsible for vein of Galen
RT aneurysmal malformation.";
RL Brain 141:979-988(2018).
RN [23]
RP VARIANT GLY-509, CHARACTERIZATION OF VARIANT GLY-509, VARIANTS CMAVM2
RP ASN-650 AND LEU-867, CHARACTERIZATION OF VARIANTS CMAVM2 ASN-650 AND
RP LEU-867, INVOLVEMENT IN CMAVM2, FUNCTION, AND INTERACTION WITH RASA1.
RX PubMed=30578106; DOI=10.1016/j.neuron.2018.11.041;
RA Duran D., Zeng X., Jin S.C., Choi J., Nelson-Williams C., Yatsula B.,
RA Gaillard J., Furey C.G., Lu Q., Timberlake A.T., Dong W., Sorscher M.A.,
RA Loring E., Klein J., Allocco A., Hunt A., Conine S., Karimy J.K.,
RA Youngblood M.W., Zhang J., DiLuna M.L., Matouk C.C., Mane S.,
RA Tikhonova I.R., Castaldi C., Lopez-Giraldez F., Knight J., Haider S.,
RA Soban M., Alper S.L., Komiyama M., Ducruet A.F., Zabramski J.M., Dardik A.,
RA Walcott B.P., Stapleton C.J., Aagaard-Kienitz B., Rodesch G., Jackson E.,
RA Smith E.R., Orbach D.B., Berenstein A., Bilguvar K., Vikkula M., Gunel M.,
RA Lifton R.P., Kahle K.T.;
RT "Mutations in chromatin modifier and ephrin signaling genes in vein of
RT Galen malformation.";
RL Neuron 101:429-443(2019).
CC -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously
CC transmembrane ephrin-B family ligands residing on adjacent cells,
CC leading to contact-dependent bidirectional signaling into neighboring
CC cells. The signaling pathway downstream of the receptor is referred to
CC as forward signaling while the signaling pathway downstream of the
CC ephrin ligand is referred to as reverse signaling. Together with its
CC cognate ligand/functional ligand EFNB2 it is involved in the regulation
CC of cell adhesion and migration, and plays a central role in heart
CC morphogenesis, angiogenesis and blood vessel remodeling and
CC permeability. EPHB4-mediated forward signaling controls cellular
CC repulsion and segregation from EFNB2-expressing cells.
CC {ECO:0000269|PubMed:12734395, ECO:0000269|PubMed:16424904,
CC ECO:0000269|PubMed:27400125, ECO:0000269|PubMed:30578106}.
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 -!- SUBUNIT: Heterotetramer upon binding of the ligand. The heterotetramer
CC is composed of an ephrin dimer and a receptor dimer. Oligomerization is
CC probably required to induce biological responses (By similarity).
CC Interacts with RASA1; the interaction depends on EPHB4 tyrosine-
CC phosphorylation (PubMed:30578106). {ECO:0000250,
CC ECO:0000269|PubMed:30578106}.
CC -!- INTERACTION:
CC P54760; P52799: EFNB2; NbExp=3; IntAct=EBI-702121, EBI-7532268;
CC P54760; P01588: EPO; NbExp=6; IntAct=EBI-702121, EBI-1027362;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28687708,
CC ECO:0000269|PubMed:8188704}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:8188704}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P54760-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P54760-2; Sequence=VSP_056024, VSP_056025;
CC Name=3;
CC IsoId=P54760-3; Sequence=VSP_056020, VSP_056021;
CC Name=4;
CC IsoId=P54760-4; Sequence=VSP_056022, VSP_056023;
CC -!- TISSUE SPECIFICITY: Abundantly expressed in placenta but also detected
CC in kidney, liver, lung, pancreas, skeletal muscle and heart. Expressed
CC in primitive and myeloid, but not lymphoid, hematopoietic cells. Also
CC observed in cell lines derived from liver, breast, colon, lung,
CC melanocyte and cervix. {ECO:0000269|PubMed:8188704}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal heart, lung, liver and to a
CC lower extent in brain. Not expressed in adult brain.
CC {ECO:0000269|PubMed:8188704}.
CC -!- PTM: Phosphorylated; autophosphorylation is stimulated by EFNB2.
CC -!- DISEASE: Lymphatic malformation 7 (LMPHM7) [MIM:617300]: A form of
CC primary lymphedema, a disease characterized by swelling of body parts
CC due to developmental anomalies and functional defects of the lymphatic
CC system. Patients with lymphedema may suffer from recurrent local
CC infections. LMPHM7 is an autosomal dominant form with variable
CC expressivity. Some individuals present with severe non-immune hydrops
CC fetalis, which may cause perinatal demise or fully resolve after the
CC neonatal period. Others present with no edema and have milder clinical
CC features, such as atrial septal defect or varicose veins as adults.
CC {ECO:0000269|PubMed:27400125}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Capillary malformation-arteriovenous malformation 2 (CMAVM2)
CC [MIM:618196]: An autosomal dominant disorder characterized by multiple,
CC round to oval or more irregularly shaped macules that are pinkish red
CC in color and are randomly distributed across the body. These capillary
CC malformations are associated with either arteriovenous malformation,
CC arteriovenous fistula, or Parkes Weber syndrome.
CC {ECO:0000269|PubMed:28687708, ECO:0000269|PubMed:28730721,
CC ECO:0000269|PubMed:29444212, ECO:0000269|PubMed:30578106}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; U07695; AAA20598.1; -; mRNA.
DR EMBL; AF312032; AAK21010.1; -; Genomic_DNA.
DR EMBL; EU826608; ACF47644.1; -; mRNA.
DR EMBL; EU826609; ACF47645.1; -; mRNA.
DR EMBL; EU826610; ACF47646.1; -; mRNA.
DR EMBL; BC004264; AAH04264.1; -; mRNA.
DR EMBL; BC052804; AAH52804.1; -; mRNA.
DR CCDS; CCDS5706.1; -. [P54760-1]
DR PIR; A54092; A54092.
DR RefSeq; NP_004435.3; NM_004444.4. [P54760-1]
DR PDB; 2BBA; X-ray; 1.65 A; A=17-196.
DR PDB; 2E7H; NMR; -; A=434-529.
DR PDB; 2HLE; X-ray; 2.05 A; A=17-196.
DR PDB; 2QKQ; X-ray; 2.10 A; A/B=896-977.
DR PDB; 2VWU; X-ray; 2.00 A; A=598-899.
DR PDB; 2VWV; X-ray; 1.90 A; A=598-899.
DR PDB; 2VWW; X-ray; 1.90 A; A=598-899.
DR PDB; 2VWX; X-ray; 1.65 A; A=598-899.
DR PDB; 2VWY; X-ray; 1.65 A; A=598-899.
DR PDB; 2VWZ; X-ray; 1.65 A; A=598-899.
DR PDB; 2VX0; X-ray; 2.10 A; A=598-899.
DR PDB; 2VX1; X-ray; 1.65 A; A=598-899.
DR PDB; 2X9F; X-ray; 1.75 A; A=598-899.
DR PDB; 2XVD; X-ray; 1.70 A; A=598-899.
DR PDB; 2YN8; X-ray; 2.11 A; A/B=598-892.
DR PDB; 3ZEW; X-ray; 2.50 A; A/B=598-892.
DR PDB; 4AW5; X-ray; 2.33 A; A=605-890.
DR PDB; 4BB4; X-ray; 1.65 A; A=598-899.
DR PDB; 6FNI; X-ray; 1.47 A; A=598-892.
DR PDB; 6FNJ; X-ray; 1.24 A; A/B=598-892.
DR PDB; 6FNK; X-ray; 1.05 A; A=598-892.
DR PDB; 6FNL; X-ray; 1.27 A; A=598-892.
DR PDB; 6FNM; X-ray; 1.16 A; A=598-892.
DR PDBsum; 2BBA; -.
DR PDBsum; 2E7H; -.
DR PDBsum; 2HLE; -.
DR PDBsum; 2QKQ; -.
DR PDBsum; 2VWU; -.
DR PDBsum; 2VWV; -.
DR PDBsum; 2VWW; -.
DR PDBsum; 2VWX; -.
DR PDBsum; 2VWY; -.
DR PDBsum; 2VWZ; -.
DR PDBsum; 2VX0; -.
DR PDBsum; 2VX1; -.
DR PDBsum; 2X9F; -.
DR PDBsum; 2XVD; -.
DR PDBsum; 2YN8; -.
DR PDBsum; 3ZEW; -.
DR PDBsum; 4AW5; -.
DR PDBsum; 4BB4; -.
DR PDBsum; 6FNI; -.
DR PDBsum; 6FNJ; -.
DR PDBsum; 6FNK; -.
DR PDBsum; 6FNL; -.
DR PDBsum; 6FNM; -.
DR AlphaFoldDB; P54760; -.
DR BMRB; P54760; -.
DR SMR; P54760; -.
DR BioGRID; 108364; 105.
DR IntAct; P54760; 33.
DR MINT; P54760; -.
DR STRING; 9606.ENSP00000350896; -.
DR BindingDB; P54760; -.
DR ChEMBL; CHEMBL5147; -.
DR DrugBank; DB07256; 3-({4-[(5-CHLORO-1,3-BENZODIOXOL-4-YL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZAMIDE.
DR DrugBank; DB07252; 3-({4-[(5-chloro-1,3-benzodioxol-4-yl)amino]pyrimidin-2-yl}amino)benzenesulfonamide.
DR DrugBank; DB01254; Dasatinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB07251; N'-(3-CHLORO-4-METHOXY-PHENYL)-N-(3,4,5-TRIMETHOXYPHENYL)-1,3,5-TRIAZINE-2,4-DIAMINE.
DR DrugBank; DB07250; N'-(5-CHLORO-1,3-BENZODIOXOL-4-YL)-N-(3,4,5- TRIMETHOXYPHENYL)PYRIMIDINE-2,4-DIAMINE.
DR DrugBank; DB07253; N'-(5-chloro-1,3-benzodioxol-4-yl)-N-(3-methylsulfonylphenyl)pyrimidine-2,4-diamine.
DR DrugBank; DB07255; N'-(5-CHLORO-1,3-BENZODIOXOL-4-YL)-N-(3-MORPHOLIN-4-YLPHENYL)PYRIMIDINE-2,4-DIAMINE.
DR DrugBank; DB07249; N-(5-chloro-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-amine.
DR DrugBank; DB07254; N-[3-[[4-[(5-CHLORO-1,3-BENZODIOXOL-4-YL)AMINO]PYRIMIDIN-2-YL]AMINO]PHENYL]METHANESULFONAMIDE.
DR DrugBank; DB11973; Tesevatinib.
DR DrugCentral; P54760; -.
DR GuidetoPHARMACOLOGY; 1833; -.
DR TCDB; 8.A.23.1.15; the basigin (basigin) family.
DR GlyConnect; 1214; 3 N-Linked glycans (1 site).
DR GlyGen; P54760; 3 sites, 3 N-linked glycans (1 site).
DR iPTMnet; P54760; -.
DR PhosphoSitePlus; P54760; -.
DR SwissPalm; P54760; -.
DR BioMuta; EPHB4; -.
DR DMDM; 19860819; -.
DR DOSAC-COBS-2DPAGE; P54760; -.
DR CPTAC; CPTAC-2788; -.
DR EPD; P54760; -.
DR jPOST; P54760; -.
DR MassIVE; P54760; -.
DR MaxQB; P54760; -.
DR PaxDb; P54760; -.
DR PeptideAtlas; P54760; -.
DR PRIDE; P54760; -.
DR ProteomicsDB; 56715; -. [P54760-1]
DR Antibodypedia; 4623; 701 antibodies from 41 providers.
DR CPTC; P54760; 2 antibodies.
DR DNASU; 2050; -.
DR Ensembl; ENST00000358173.8; ENSP00000350896.3; ENSG00000196411.10. [P54760-1]
DR Ensembl; ENST00000616502.4; ENSP00000482702.1; ENSG00000196411.10. [P54760-3]
DR GeneID; 2050; -.
DR KEGG; hsa:2050; -.
DR MANE-Select; ENST00000358173.8; ENSP00000350896.3; NM_004444.5; NP_004435.3.
DR UCSC; uc011kkg.2; human. [P54760-1]
DR CTD; 2050; -.
DR DisGeNET; 2050; -.
DR GeneCards; EPHB4; -.
DR GeneReviews; EPHB4; -.
DR HGNC; HGNC:3395; EPHB4.
DR HPA; ENSG00000196411; Low tissue specificity.
DR MalaCards; EPHB4; -.
DR MIM; 600011; gene.
DR MIM; 617300; phenotype.
DR MIM; 618196; phenotype.
DR neXtProt; NX_P54760; -.
DR NIAGADS; ENSG00000196411; -.
DR OpenTargets; ENSG00000196411; -.
DR Orphanet; 137667; Capillary malformation-arteriovenous malformation.
DR Orphanet; 90186; Meige disease.
DR Orphanet; 1053; Vein of Galen aneurysmal malformation.
DR PharmGKB; PA27827; -.
DR VEuPathDB; HostDB:ENSG00000196411; -.
DR eggNOG; KOG0196; Eukaryota.
DR GeneTree; ENSGT00940000160057; -.
DR HOGENOM; CLU_000288_141_3_1; -.
DR InParanoid; P54760; -.
DR OMA; TAHWLRT; -.
DR OrthoDB; 933071at2759; -.
DR PhylomeDB; P54760; -.
DR TreeFam; TF315608; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P54760; -.
DR Reactome; R-HSA-2682334; EPH-Ephrin signaling.
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-HSA-3928664; Ephrin signaling.
DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells.
DR SignaLink; P54760; -.
DR SIGNOR; P54760; -.
DR BioGRID-ORCS; 2050; 13 hits in 1109 CRISPR screens.
DR ChiTaRS; EPHB4; human.
DR EvolutionaryTrace; P54760; -.
DR GeneWiki; EPH_receptor_B4; -.
DR GenomeRNAi; 2050; -.
DR Pharos; P54760; Tchem.
DR PRO; PR:P54760; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P54760; protein.
DR Bgee; ENSG00000196411; Expressed in olfactory bulb and 207 other tissues.
DR ExpressionAtlas; P54760; baseline and differential.
DR Genevisible; P54760; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005003; F:ephrin receptor activity; IDA:UniProtKB.
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:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IDA:UniProtKB.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; IDA:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0003007; P:heart morphogenesis; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10474; EphR_LBD_B4; 1.
DR CDD; cd00063; FN3; 2.
DR CDD; cd09554; SAM_EPH-B4; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR037636; EPH-B4_SAM.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR034290; EphB4_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; IPR011641; Tyr-kin_ephrin_A/B_rcpt-like.
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; PF07699; Ephrin_rec_like; 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; PS01186; EGF_2; 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; ATP-binding;
KW Cell membrane; Developmental protein; Disease variant; Disulfide bond;
KW Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT CHAIN 16..987
FT /note="Ephrin type-B receptor 4"
FT /id="PRO_0000016834"
FT TOPO_DOM 16..539
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 540..560
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 561..987
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 17..202
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 323..432
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 436..529
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 615..899
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 907..971
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 965..987
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 985..987
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 740
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 621..629
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 647
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 769
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 770
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 911
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 943
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 976
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 987
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT CARBOHYD 203
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 426
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 61..184
FT DISULFID 97..107
FT VAR_SEQ 270..306
FT /note="ACAQGTFKPLSGEGSCQPCPANSHSNTIGSAVCQCRV -> GRRGSQQRAVP
FT EDVRKPGRAAGAEAGSQLPGAGTGAL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_056020"
FT VAR_SEQ 307..987
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_056021"
FT VAR_SEQ 406..414
FT /note="VTALNGVSS -> YLLQCLTSG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_056022"
FT VAR_SEQ 415..987
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_056023"
FT VAR_SEQ 507..516
FT /note="VRARSEAGYG -> RARAGGSSWP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_056024"
FT VAR_SEQ 517..987
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_056025"
FT VARIANT 59
FT /note="E -> K (in CMAVM2; unknown pathological
FT significance; dbSNP:rs1584667224)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081689"
FT VARIANT 67
FT /note="P -> L (in dbSNP:rs34653459)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042181"
FT VARIANT 74
FT /note="R -> P (in CMAVM2; unknown pathological
FT significance; dbSNP:rs61735971)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081690"
FT VARIANT 107
FT /note="C -> R (in CMAVM2; unknown pathological
FT significance; dbSNP:rs1562974383)"
FT /evidence="ECO:0000269|PubMed:29444212"
FT /id="VAR_081691"
FT VARIANT 113
FT /note="V -> I (in dbSNP:rs55866373)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042182"
FT VARIANT 115
FT /note="Missing (in CMAVM2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081692"
FT VARIANT 130..987
FT /note="Missing (in CMAVM2)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081693"
FT VARIANT 161..162
FT /note="VK -> L (in CMAVM2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081694"
FT VARIANT 162
FT /note="K -> R (in dbSNP:rs17854760)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_071163"
FT VARIANT 187
FT /note="L -> P (in CMAVM2; unknown pathological
FT significance; dbSNP:rs1584666053)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081695"
FT VARIANT 244..987
FT /note="Missing (in CMAVM2)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081696"
FT VARIANT 268
FT /note="C -> R (in CMAVM2; unknown pathological
FT significance; dbSNP:rs201816920)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081697"
FT VARIANT 346
FT /note="P -> L (in a metastatic melanoma sample; somatic
FT mutation; dbSNP:rs267601191)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042183"
FT VARIANT 352..987
FT /note="Missing (in CMAVM2)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081698"
FT VARIANT 371
FT /note="A -> V (in dbSNP:rs55720981)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042184"
FT VARIANT 375..987
FT /note="Missing (in CMAVM2)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081699"
FT VARIANT 431..987
FT /note="Missing (in CMAVM2)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081700"
FT VARIANT 469
FT /note="V -> G (in CMAVM2; unknown pathological
FT significance; dbSNP:rs1584662591)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081701"
FT VARIANT 509
FT /note="A -> G (does not affect tyrosine phosphorylation;
FT does not affect interaction with RASA1; dbSNP:rs146937374)"
FT /evidence="ECO:0000269|PubMed:30578106"
FT /id="VAR_081702"
FT VARIANT 516
FT /note="G -> R (in CMAVM2; unknown pathological
FT significance; dbSNP:rs776305185)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081703"
FT VARIANT 520..987
FT /note="Missing (in CMAVM2)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081704"
FT VARIANT 576
FT /note="D -> E (in dbSNP:rs36050247)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042185"
FT VARIANT 596..987
FT /note="Missing (in CMAVM2)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081705"
FT VARIANT 650
FT /note="K -> N (in CMAVM2; highly decreased tyrosine
FT phosphorylation; highly decreased interaction with RASA1;
FT dbSNP:rs1584658113)"
FT /evidence="ECO:0000269|PubMed:30578106"
FT /id="VAR_081706"
FT VARIANT 656
FT /note="R -> W (in CMAVM2; unknown pathological
FT significance; dbSNP:rs745584371)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081707"
FT VARIANT 664
FT /note="E -> K (in CMAVM2; the mutant protein is not
FT detected by Western blot; loss of localization to cell
FT membrane; dbSNP:rs1562969219)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081708"
FT VARIANT 678
FT /note="R -> H (in dbSNP:rs55692440)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042186"
FT VARIANT 725
FT /note="A -> T (in CMAVM2; unknown pathological
FT significance; dbSNP:rs1159930961)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081709"
FT VARIANT 739..987
FT /note="Missing (in CMAVM2)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081710"
FT VARIANT 739
FT /note="R -> Q (in LMPHM7; loss of kinase activity;
FT dbSNP:rs1057519263)"
FT /evidence="ECO:0000269|PubMed:27400125"
FT /id="VAR_078063"
FT VARIANT 745
FT /note="N -> D (in CMAVM2; dbSNP:rs1584654433)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081711"
FT VARIANT 782
FT /note="I -> S (in LMPHM7; loss of kinase activity;
FT dbSNP:rs1057519264)"
FT /evidence="ECO:0000269|PubMed:27400125"
FT /id="VAR_078064"
FT VARIANT 789
FT /note="P -> R (in CMAVM2; unknown pathological
FT significance; dbSNP:rs753075600)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081712"
FT VARIANT 789
FT /note="P -> S (in CMAVM2; unknown pathological
FT significance; dbSNP:rs1417508111)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081713"
FT VARIANT 802
FT /note="D -> G (in CMAVM2; dbSNP:rs776410552)"
FT /evidence="ECO:0000269|PubMed:28730721"
FT /id="VAR_081714"
FT VARIANT 806..987
FT /note="Missing (in CMAVM2)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081715"
FT VARIANT 807
FT /note="G -> R (in CMAVM2; unknown pathological
FT significance; dbSNP:rs1330628156)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081716"
FT VARIANT 820
FT /note="P -> L (in CMAVM2; unknown pathological
FT significance; dbSNP:rs1584653650)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081717"
FT VARIANT 820
FT /note="P -> T (in CMAVM2; unknown pathological
FT significance; dbSNP:rs1584653653)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081718"
FT VARIANT 838
FT /note="R -> W (in CMAVM2; the mutant protein is not
FT detected by Western blot; loss of localization to cell
FT membrane; dbSNP:rs764827256)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081719"
FT VARIANT 845
FT /note="C -> R (in CMAVM2; the mutant protein is not
FT detected by Western blot; loss of localization to cell
FT membrane; dbSNP:rs1584653054)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081720"
FT VARIANT 856
FT /note="C -> Y (in CMAVM2; dbSNP:rs1584653005)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081721"
FT VARIANT 864
FT /note="R -> W (in CMAVM2; the mutant protein is not
FT detected by Western blot; loss of localization to cell
FT membrane; dbSNP:rs769965440)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081722"
FT VARIANT 867
FT /note="F -> L (in CMAVM2; loss of tyrosine phosphorylation;
FT loss of interaction with RASA1; dbSNP:rs1584652949)"
FT /evidence="ECO:0000269|PubMed:30578106"
FT /id="VAR_081723"
FT VARIANT 870
FT /note="V -> E (in CMAVM2; unknown pathological
FT significance; dbSNP:rs1584652920)"
FT /evidence="ECO:0000269|PubMed:29444212"
FT /id="VAR_081724"
FT VARIANT 874
FT /note="L -> P (in CMAVM2; unknown pathological
FT significance; dbSNP:rs1584652900)"
FT /evidence="ECO:0000269|PubMed:28687708"
FT /id="VAR_081725"
FT VARIANT 882
FT /note="A -> T (in dbSNP:rs34918225)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042187"
FT VARIANT 889
FT /note="R -> W (in a gastric adenocarcinoma sample; somatic
FT mutation; dbSNP:rs762016655)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042188"
FT VARIANT 890
FT /note="E -> D (in dbSNP:rs35638378)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042189"
FT MUTAGEN 95
FT /note="L->R: Reduces binding affinity for EFNB2."
FT /evidence="ECO:0000269|PubMed:16867992"
FT CONFLICT 62
FT /note="D -> E (in Ref. 1; AAA20598)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="Y -> D (in Ref. 1; AAA20598)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="V -> W (in Ref. 1; AAA20598)"
FT /evidence="ECO:0000305"
FT CONFLICT 926..927
FT /note="ES -> AR (in Ref. 1; AAA20598)"
FT /evidence="ECO:0000305"
FT STRAND 17..22
FT /evidence="ECO:0007829|PDB:2BBA"
FT HELIX 23..25
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 33..36
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 54..61
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 70..74
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 84..95
FT /evidence="ECO:0007829|PDB:2BBA"
FT HELIX 97..99
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 109..121
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 135..142
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:2HLE"
FT TURN 151..153
FT /evidence="ECO:0007829|PDB:2HLE"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:2HLE"
FT STRAND 160..166
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 171..182
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 184..196
FT /evidence="ECO:0007829|PDB:2BBA"
FT STRAND 441..446
FT /evidence="ECO:0007829|PDB:2E7H"
FT STRAND 449..453
FT /evidence="ECO:0007829|PDB:2E7H"
FT STRAND 460..462
FT /evidence="ECO:0007829|PDB:2E7H"
FT STRAND 466..473
FT /evidence="ECO:0007829|PDB:2E7H"
FT TURN 479..481
FT /evidence="ECO:0007829|PDB:2E7H"
FT STRAND 482..496
FT /evidence="ECO:0007829|PDB:2E7H"
FT STRAND 503..510
FT /evidence="ECO:0007829|PDB:2E7H"
FT HELIX 612..614
FT /evidence="ECO:0007829|PDB:6FNK"
FT STRAND 615..623
FT /evidence="ECO:0007829|PDB:6FNK"
FT STRAND 625..634
FT /evidence="ECO:0007829|PDB:6FNK"
FT STRAND 637..639
FT /evidence="ECO:0007829|PDB:6FNJ"
FT STRAND 642..649
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 655..668
FT /evidence="ECO:0007829|PDB:6FNK"
FT STRAND 679..683
FT /evidence="ECO:0007829|PDB:6FNK"
FT STRAND 685..694
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 701..707
FT /evidence="ECO:0007829|PDB:6FNK"
FT TURN 708..710
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 714..733
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 743..745
FT /evidence="ECO:0007829|PDB:6FNK"
FT STRAND 746..748
FT /evidence="ECO:0007829|PDB:6FNK"
FT STRAND 754..756
FT /evidence="ECO:0007829|PDB:6FNK"
FT STRAND 761..763
FT /evidence="ECO:0007829|PDB:6FNI"
FT HELIX 765..767
FT /evidence="ECO:0007829|PDB:2VWX"
FT HELIX 784..786
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 789..794
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 799..814
FT /evidence="ECO:0007829|PDB:6FNK"
FT TURN 815..817
FT /evidence="ECO:0007829|PDB:6FNI"
FT TURN 820..823
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 826..834
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 847..856
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 861..863
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 867..879
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 881..884
FT /evidence="ECO:0007829|PDB:6FNK"
FT HELIX 912..918
FT /evidence="ECO:0007829|PDB:2QKQ"
FT HELIX 922..924
FT /evidence="ECO:0007829|PDB:2QKQ"
FT HELIX 925..930
FT /evidence="ECO:0007829|PDB:2QKQ"
FT HELIX 936..939
FT /evidence="ECO:0007829|PDB:2QKQ"
FT HELIX 944..950
FT /evidence="ECO:0007829|PDB:2QKQ"
FT HELIX 955..965
FT /evidence="ECO:0007829|PDB:2QKQ"
SQ SEQUENCE 987 AA; 108270 MW; 11A004622F194706 CRC64;
MELRVLLCWA SLAAALEETL LNTKLETADL KWVTFPQVDG QWEELSGLDE EQHSVRTYEV
CDVQRAPGQA HWLRTGWVPR RGAVHVYATL RFTMLECLSL PRAGRSCKET FTVFYYESDA
DTATALTPAW MENPYIKVDT VAAEHLTRKR PGAEATGKVN VKTLRLGPLS KAGFYLAFQD
QGACMALLSL HLFYKKCAQL TVNLTRFPET VPRELVVPVA GSCVVDAVPA PGPSPSLYCR
EDGQWAEQPV TGCSCAPGFE AAEGNTKCRA CAQGTFKPLS GEGSCQPCPA NSHSNTIGSA
VCQCRVGYFR ARTDPRGAPC TTPPSAPRSV VSRLNGSSLH LEWSAPLESG GREDLTYALR
CRECRPGGSC APCGGDLTFD PGPRDLVEPW VVVRGLRPDF TYTFEVTALN GVSSLATGPV
PFEPVNVTTD REVPPAVSDI RVTRSSPSSL SLAWAVPRAP SGAVLDYEVK YHEKGAEGPS
SVRFLKTSEN RAELRGLKRG ASYLVQVRAR SEAGYGPFGQ EHHSQTQLDE SEGWREQLAL
IAGTAVVGVV LVLVVIVVAV LCLRKQSNGR EAEYSDKHGQ YLIGHGTKVY IDPFTYEDPN
EAVREFAKEI DVSYVKIEEV IGAGEFGEVC RGRLKAPGKK ESCVAIKTLK GGYTERQRRE
FLSEASIMGQ FEHPNIIRLE GVVTNSMPVM ILTEFMENGA LDSFLRLNDG QFTVIQLVGM
LRGIASGMRY LAEMSYVHRD LAARNILVNS NLVCKVSDFG LSRFLEENSS DPTYTSSLGG
KIPIRWTAPE AIAFRKFTSA SDAWSYGIVM WEVMSFGERP YWDMSNQDVI NAIEQDYRLP
PPPDCPTSLH QLMLDCWQKD RNARPRFPQV VSALDKMIRN PASLKIVARE NGGASHPLLD
QRQPHYSAFG SVGEWLRAIK MGRYEESFAA AGFGSFELVS QISAEDLLRI GVTLAGHQKK
ILASVQHMKS QAKPGTPGGT GGPAPQY
