EPHB6_HUMAN
ID EPHB6_HUMAN Reviewed; 1021 AA.
AC O15197; A4D2I7; A8CDT5; D3DXD3; Q2TB23; Q2TB24;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 4.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Ephrin type-B receptor 6;
DE AltName: Full=HEP;
DE AltName: Full=Tyrosine-protein kinase-defective receptor EPH-6;
DE Flags: Precursor;
GN Name=EPHB6;
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), AND TISSUE SPECIFICITY.
RX PubMed=9207182; DOI=10.1006/bbrc.1997.6812;
RA Matsuoka H., Iwata N., Ito M., Shimoyama M., Nagata A., Chihara K.,
RA Takai S., Matsui T.;
RT "Expression of a kinase-defective Eph-like receptor in the normal human
RT brain.";
RL Biochem. Biophys. Res. Commun. 235:487-492(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-122; ARG-282; ALA-324
RP AND GLN-499.
RG SeattleSNPs variation discovery resource;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-1021 (ISOFORM 3).
RX PubMed=18425388;
RA Jin M., Komohara Y., Shichijo S., Harada M., Yamanaka R., Miyamoto S.,
RA Nikawa J., Itoh K., Yamada A.;
RT "Identification of EphB6 variant-derived epitope peptides recognized by
RT cytotoxic T-lymphocytes from HLA-A24+ malignant glioma patients.";
RL Oncol. Rep. 19:1277-1283(2008).
RN [8]
RP PROTEIN SEQUENCE OF 32-46.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [9]
RP INTERACTION WITH CBL AND EPHB1, AND PHOSPHORYLATION.
RX PubMed=11713248; DOI=10.1074/jbc.m108011200;
RA Freywald A., Sharfe N., Roifman C.M.;
RT "The kinase-null EphB6 receptor undergoes transphosphorylation in a complex
RT with EphB1.";
RL J. Biol. Chem. 277:3823-3828(2002).
RN [10]
RP FUNCTION.
RX PubMed=12517763; DOI=10.1074/jbc.m208179200;
RA Freywald A., Sharfe N., Rashotte C., Grunberger T., Roifman C.M.;
RT "The EphB6 receptor inhibits JNK activation in T lymphocytes and modulates
RT T cell receptor-mediated responses.";
RL J. Biol. Chem. 278:10150-10156(2003).
RN [11]
RP FUNCTION, INTERACTION WITH FYN, AND PHOSPHORYLATION.
RX PubMed=15955811; DOI=10.1074/jbc.m500010200;
RA Matsuoka H., Obama H., Kelly M.L., Matsui T., Nakamoto M.;
RT "Biphasic functions of the kinase-defective Ephb6 receptor in cell adhesion
RT and migration.";
RL J. Biol. Chem. 280:29355-29363(2005).
RN [12]
RP TISSUE SPECIFICITY.
RX PubMed=18754880; DOI=10.1111/j.1349-7006.2008.00866.x;
RA Jin M., Komohara Y., Shichijo S., Yamanaka R., Nikawa J., Itoh K.,
RA Yamada A.;
RT "Erythropoietin-producing hepatocyte B6 variant-derived peptides with the
RT ability to induce glioma-reactive cytotoxic T lymphocytes in human
RT leukocyte antigen-A2+ glioma patients.";
RL Cancer Sci. 99:1656-1662(2008).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=19234485; DOI=10.1038/onc.2009.18;
RA Fox B.P., Kandpal R.P.;
RT "EphB6 receptor significantly alters invasiveness and other phenotypic
RT characteristics of human breast carcinoma cells.";
RL Oncogene 28:1706-1713(2009).
RN [14]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-360; PRO-603; GLN-719 AND GLY-930.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [15]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-122; THR-170; VAL-221; HIS-282;
RP GLN-309; ALA-324; LEU-332; VAL-662; SER-743; HIS-813; LYS-875 AND VAL-993.
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).
CC -!- FUNCTION: Kinase-defective receptor for members of the ephrin-B family.
CC Binds to ephrin-B1 and ephrin-B2. Modulates cell adhesion and migration
CC by exerting both positive and negative effects upon stimulation with
CC ephrin-B2. Inhibits JNK activation, T-cell receptor-induced IL-2
CC secretion and CD25 expression upon stimulation with ephrin-B2.
CC {ECO:0000269|PubMed:12517763, ECO:0000269|PubMed:15955811}.
CC -!- SUBUNIT: Interacts with CBL and EPHB1. Interacts with FYN; this
CC interaction takes place in a ligand-independent manner.
CC {ECO:0000269|PubMed:11713248, ECO:0000269|PubMed:15955811}.
CC -!- INTERACTION:
CC O15197-2; O95994: AGR2; NbExp=3; IntAct=EBI-10182490, EBI-712648;
CC O15197-2; Q8WXK4-2: ASB12; NbExp=3; IntAct=EBI-10182490, EBI-18394052;
CC O15197-2; Q9H2G9: BLZF1; NbExp=3; IntAct=EBI-10182490, EBI-2548012;
CC O15197-2; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-10182490, EBI-742054;
CC O15197-2; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-10182490, EBI-747204;
CC O15197-2; Q0VD86: INCA1; NbExp=8; IntAct=EBI-10182490, EBI-6509505;
CC O15197-2; P35548: MSX2; NbExp=3; IntAct=EBI-10182490, EBI-6447480;
CC O15197-2; Q5VT66: MTARC1; NbExp=3; IntAct=EBI-10182490, EBI-11903927;
CC O15197-2; Q9GZT8: NIF3L1; NbExp=3; IntAct=EBI-10182490, EBI-740897;
CC O15197-2; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-10182490, EBI-945833;
CC O15197-2; P78424: POU6F2; NbExp=3; IntAct=EBI-10182490, EBI-12029004;
CC O15197-2; O14744: PRMT5; NbExp=3; IntAct=EBI-10182490, EBI-351098;
CC O15197-2; Q04864: REL; NbExp=3; IntAct=EBI-10182490, EBI-307352;
CC O15197-2; Q04864-2: REL; NbExp=3; IntAct=EBI-10182490, EBI-10829018;
CC O15197-2; Q99081-3: TCF12; NbExp=3; IntAct=EBI-10182490, EBI-11952764;
CC O15197-2; P15884: TCF4; NbExp=3; IntAct=EBI-10182490, EBI-533224;
CC O15197-2; P15884-3: TCF4; NbExp=3; IntAct=EBI-10182490, EBI-13636688;
CC O15197-2; Q96M29: TEKT5; NbExp=3; IntAct=EBI-10182490, EBI-10239812;
CC O15197-2; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-10182490, EBI-492476;
CC O15197-2; Q9HCM9: TRIM39; NbExp=3; IntAct=EBI-10182490, EBI-739510;
CC O15197-2; Q9HCM9-2: TRIM39; NbExp=5; IntAct=EBI-10182490, EBI-11523450;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O15197-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O15197-2; Sequence=VSP_037496;
CC Name=3; Synonyms=EphB6v;
CC IsoId=O15197-3; Sequence=VSP_037497, VSP_037498;
CC -!- TISSUE SPECIFICITY: Expressed in brain. Expressed in non invasive
CC breast carcinoma cell lines (at protein level). Strong expression in
CC brain and pancreas, and weak expression in other tissues, such as
CC heart, placenta, lung, liver, skeletal muscle and kidney. Expressed in
CC breast non invasive tumors but not in metastatic lesions. Isoform 3 is
CC expressed in cell lines of glioblastomas, anaplastic astrocytomas,
CC gliosarcomas and astrocytomas. Isoform 3 is not detected in normal
CC tissues. {ECO:0000269|PubMed:18754880, ECO:0000269|PubMed:19234485,
CC ECO:0000269|PubMed:9207182}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive. Its extracellular domain is capable of promoting cell
CC adhesion and migration in response to low concentrations of ephrin-B2,
CC but its cytoplasmic domain is essential for cell repulsion and
CC inhibition of migration induced by high concentrations of ephrin-B2.
CC -!- PTM: Ligand-binding increases phosphorylation on tyrosine residues.
CC Phosphorylation on tyrosine residues is mediated by
CC transphosphorylation by the catalytically active EPHB1 in a ligand-
CC independent manner. Tyrosine phosphorylation of the receptor may act as
CC a switch on the functional transition from cell adhesion/attraction to
CC de-adhesion/repulsion. {ECO:0000269|PubMed:11713248,
CC ECO:0000269|PubMed:15955811}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD03058.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI10608.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAP20939.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA21560.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAL23775.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=EAW51902.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/ephb6/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/EPHB6ID40471ch7q34.html";
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DR EMBL; D83492; BAA21560.1; ALT_INIT; mRNA.
DR EMBL; AY280502; AAP20939.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF107256; AAD03058.1; ALT_INIT; Genomic_DNA.
DR EMBL; AC104597; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236959; EAL23775.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471198; EAW51900.1; -; Genomic_DNA.
DR EMBL; CH471198; EAW51901.1; -; Genomic_DNA.
DR EMBL; CH471198; EAW51902.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471198; EAW51903.1; -; Genomic_DNA.
DR EMBL; BC051028; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC110606; AAI10607.1; -; mRNA.
DR EMBL; BC110607; AAI10608.2; ALT_INIT; mRNA.
DR EMBL; EU054308; ABV55388.1; -; mRNA.
DR PIR; JC5526; JC5526.
DR RefSeq; NP_001267724.2; NM_001280795.2.
DR RefSeq; NP_004436.4; NM_004445.5.
DR PDB; 7K7J; X-ray; 3.00 A; A=33-578.
DR PDBsum; 7K7J; -.
DR AlphaFoldDB; O15197; -.
DR SMR; O15197; -.
DR BioGRID; 108365; 43.
DR IntAct; O15197; 28.
DR MINT; O15197; -.
DR STRING; 9606.ENSP00000481994; -.
DR BindingDB; O15197; -.
DR ChEMBL; CHEMBL5836; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; O15197; -.
DR GlyGen; O15197; 1 site.
DR iPTMnet; O15197; -.
DR PhosphoSitePlus; O15197; -.
DR BioMuta; EPHB6; -.
DR jPOST; O15197; -.
DR MassIVE; O15197; -.
DR PaxDb; O15197; -.
DR PeptideAtlas; O15197; -.
DR PRIDE; O15197; -.
DR ProteomicsDB; 48502; -. [O15197-1]
DR ProteomicsDB; 48503; -. [O15197-2]
DR ProteomicsDB; 48504; -. [O15197-3]
DR ABCD; O15197; 7 sequenced antibodies.
DR DNASU; 2051; -.
DR GeneID; 2051; -.
DR KEGG; hsa:2051; -.
DR CTD; 2051; -.
DR DisGeNET; 2051; -.
DR GeneCards; EPHB6; -.
DR HGNC; HGNC:3396; EPHB6.
DR MIM; 602757; gene.
DR neXtProt; NX_O15197; -.
DR PharmGKB; PA27828; -.
DR eggNOG; KOG0196; Eukaryota.
DR InParanoid; O15197; -.
DR OrthoDB; 933071at2759; -.
DR PhylomeDB; O15197; -.
DR TreeFam; TF314013; -.
DR PathwayCommons; O15197; -.
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; O15197; -.
DR BioGRID-ORCS; 2051; 7 hits in 1011 CRISPR screens.
DR ChiTaRS; EPHB6; human.
DR GeneWiki; EPHB6; -.
DR GenomeRNAi; 2051; -.
DR Pharos; O15197; Tchem.
DR PRO; PR:O15197; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; O15197; protein.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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; TAS:ProtInc.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; IBA:GO_Central.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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; 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; 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; 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; PF07647; SAM_2; 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 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; PS50011; PROTEIN_KINASE_DOM; 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; ATP-binding; Direct protein sequencing;
KW Glycoprotein; Membrane; Nucleotide-binding; Receptor; Reference proteome;
KW Repeat; Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 32..1021
FT /note="Ephrin type-B receptor 6"
FT /id="PRO_0000016837"
FT TOPO_DOM 32..594
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 595..615
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 616..1021
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 33..237
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 369..486
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 487..582
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 670..919
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 948..1012
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 163..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1019..1021
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 163..179
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 676..684
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 16..292
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037496"
FT VAR_SEQ 487..540
FT /note="VPSAVPVVHQVSRASNSITVSWPQPDQTNGNILDYQLRYYDQAEDESHSFTL
FT TS -> GELFSLAFRIPCLRSFEPPSLLLISSLVHPCRPPLKADPAPRDSYPHNNFPFA
FT L (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18425388"
FT /id="VSP_037497"
FT VAR_SEQ 541..1021
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18425388"
FT /id="VSP_037498"
FT VARIANT 122
FT /note="G -> S (in dbSNP:rs8177173)"
FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.2"
FT /id="VAR_019139"
FT VARIANT 170
FT /note="S -> T"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042190"
FT VARIANT 221
FT /note="A -> V"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042191"
FT VARIANT 282
FT /note="P -> H"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042192"
FT VARIANT 282
FT /note="P -> R (in dbSNP:rs8177143)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019140"
FT VARIANT 309
FT /note="R -> Q (in dbSNP:rs55728646)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042193"
FT VARIANT 324
FT /note="S -> A (in dbSNP:rs8177146)"
FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.2"
FT /id="VAR_019141"
FT VARIANT 332
FT /note="S -> L (in dbSNP:rs35189999)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042194"
FT VARIANT 360
FT /note="D -> N (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036091"
FT VARIANT 499
FT /note="R -> Q (in dbSNP:rs8177175)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019142"
FT VARIANT 603
FT /note="A -> P (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036092"
FT VARIANT 662
FT /note="A -> V (in dbSNP:rs35984674)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042195"
FT VARIANT 719
FT /note="R -> Q (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036093"
FT VARIANT 743
FT /note="P -> S (in an ovarian mucinous carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042196"
FT VARIANT 813
FT /note="R -> H"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042197"
FT VARIANT 875
FT /note="E -> K (in a glioblastoma multiforme sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042198"
FT VARIANT 930
FT /note="D -> G (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036094"
FT VARIANT 993
FT /note="I -> V"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042199"
FT STRAND 34..42
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:7K7J"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 101..112
FT /evidence="ECO:0007829|PDB:7K7J"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:7K7J"
FT TURN 121..123
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 126..139
FT /evidence="ECO:0007829|PDB:7K7J"
FT TURN 141..144
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 195..202
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 206..217
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 219..229
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 283..286
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 292..296
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 305..308
FT /evidence="ECO:0007829|PDB:7K7J"
FT TURN 309..312
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 313..316
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 325..328
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 374..380
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 382..390
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 402..409
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 414..416
FT /evidence="ECO:0007829|PDB:7K7J"
FT TURN 418..420
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 437..447
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 456..463
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 465..469
FT /evidence="ECO:0007829|PDB:7K7J"
FT STRAND 476..481
FT /evidence="ECO:0007829|PDB:7K7J"
SQ SEQUENCE 1021 AA; 110700 MW; BF1D4D9BE34358A5 CRC64;
MATEGAAQLG NRVAGMVCSL WVLLLVSSVL ALEEVLLDTT GETSEIGWLT YPPGGWDEVS
VLDDQRRLTR TFEACHVAGA PPGTGQDNWL QTHFVERRGA QRAHIRLHFS VRACSSLGVS
GGTCRETFTL YYRQAEEPDS PDSVSSWHLK RWTKVDTIAA DESFPSSSSS SSSSSSAAWA
VGPHGAGQRA GLQLNVKERS FGPLTQRGFY VAFQDTGACL ALVAVRLFSY TCPAVLRSFA
SFPETQASGA GGASLVAAVG TCVAHAEPEE DGVGGQAGGS PPRLHCNGEG KWMVAVGGCR
CQPGYQPARG DKACQACPRG LYKSSAGNAP CSPCPARSHA PNPAAPVCPC LEGFYRASSD
PPEAPCTGPP SAPQELWFEV QGSALMLHWR LPRELGGRGD LLFNVVCKEC EGRQEPASGG
GGTCHRCRDE VHFDPRQRGL TESRVLVGGL RAHVPYILEV QAVNGVSELS PDPPQAAAIN
VSTSHEVPSA VPVVHQVSRA SNSITVSWPQ PDQTNGNILD YQLRYYDQAE DESHSFTLTS
ETNTATVTQL SPGHIYGFQV RARTAAGHGP YGGKVYFQTL PQGELSSQLP ERLSLVIGSI
LGALAFLLLA AITVLAVVFQ RKRRGTGYTE QLQQYSSPGL GVKYYIDPST YEDPCQAIRE
LAREVDPAYI KIEEVIGTGS FGEVRQGRLQ PRGRREQTVA IQALWAGGAE SLQMTFLGRA
AVLGQFQHPN ILRLEGVVTK SRPLMVLTEF MELGPLDSFL RQREGQFSSL QLVAMQRGVA
AAMQYLSSFA FVHRSLSAHS VLVNSHLVCK VARLGHSPQG PSCLLRWAAP EVIAHGKHTT
SSDVWSFGIL MWEVMSYGER PYWDMSEQEV LNAIEQEFRL PPPPGCPPGL HLLMLDTWQK
DRARRPHFDQ LVAAFDKMIR KPDTLQAGGD PGERPSQALL TPVALDFPCL DSPQAWLSAI
GLECYQDNFS KFGLCTFSDV AQLSLEDLPA LGITLAGHQK KLLHHIQLLQ QHLRQQGSVE
V
