EPHB1_HUMAN
ID EPHB1_HUMAN Reviewed; 984 AA.
AC P54762; A8K593; B3KTB2; B5A969; O43569; O95142; O95143; Q0VG87;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Ephrin type-B receptor 1;
DE EC=2.7.10.1;
DE AltName: Full=ELK;
DE AltName: Full=EPH tyrosine kinase 2;
DE AltName: Full=EPH-like kinase 6;
DE Short=EK6;
DE Short=hEK6;
DE AltName: Full=Neuronally-expressed EPH-related tyrosine kinase;
DE Short=NET;
DE AltName: Full=Tyrosine-protein kinase receptor EPH-2;
DE Flags: Precursor;
GN Name=EPHB1; Synonyms=ELK, EPHT2, HEK6, NET;
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).
RC TISSUE=Fetal brain;
RX PubMed=8666391; DOI=10.1006/geno.1995.9985;
RA Tang X.X., Biegel J.A., Nycum L.M., Yoshioka A., Brodeur G.M.,
RA Pleasure D.E., Ikegaki N.;
RT "cDNA cloning, molecular characterization, and chromosomal localization of
RT NET(EPHT2), a human EPH-related receptor protein-tyrosine kinase gene
RT preferentially expressed in brain.";
RL Genomics 29:426-437(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN CELL ADHESION, FUNCTION
RP IN JUN CASCADE ACTIVATION, INTERACTION WITH NCK1, MUTAGENESIS OF TYR-594
RP AND LYS-651, AND VARIANT TRP-973.
RC TISSUE=Kidney;
RX PubMed=9430661; DOI=10.1074/jbc.273.3.1303;
RA Stein E., Huynh-Do U., Lane A.A., Cerretti D.P., Daniel T.O.;
RT "Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation to
RT c-Jun kinase.";
RL J. Biol. Chem. 273:1303-1308(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), 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] (ISOFORMS 1 AND 2).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 PROTEIN SEQUENCE OF 18-32.
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 [8]
RP INTERACTION WITH GRB2 AND GRB10, MUTAGENESIS OF TYR-928, AND
RP PHOSPHORYLATION AT TYR-928.
RX PubMed=8798570; DOI=10.1074/jbc.271.38.23588;
RA Stein E., Cerretti D.P., Daniel T.O.;
RT "Ligand activation of ELK receptor tyrosine kinase promotes its association
RT with Grb10 and Grb2 in vascular endothelial cells.";
RL J. Biol. Chem. 271:23588-23593(1996).
RN [9]
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 [10]
RP FUNCTION IN ANGIOGENESIS, FUNCTION IN CELL ADHESION, INTERACTION WITH ACP1,
RP AND MUTAGENESIS OF TYR-928.
RX PubMed=9499402; DOI=10.1101/gad.12.5.667;
RA Stein E., Lane A.A., Cerretti D.P., Schoecklmann H.O., Schroff A.D.,
RA Van Etten R.L., Daniel T.O.;
RT "Eph receptors discriminate specific ligand oligomers to determine
RT alternative signaling complexes, attachment, and assembly responses.";
RL Genes Dev. 12:667-678(1998).
RN [11]
RP INTERACTION WITH EPHB6.
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 [12]
RP INTERACTION WITH GRB7, FUNCTION, PHOSPHORYLATION AT TYR-928, AND
RP MUTAGENESIS OF TYR-928.
RX PubMed=12223469; DOI=10.1074/jbc.m203165200;
RA Han D.C., Shen T.L., Miao H., Wang B., Guan J.L.;
RT "EphB1 associates with Grb7 and regulates cell migration.";
RL J. Biol. Chem. 277:45655-45661(2002).
RN [13]
RP FUNCTION IN CELL MIGRATION, FUNCTION IN ERK CASCADE ACTIVATION, INTERACTION
RP WITH GRB2; SHC1 AND SRC, AND MUTAGENESIS OF TYR-600 AND TYR-778.
RX PubMed=12925710; DOI=10.1083/jcb.200302073;
RA Vindis C., Cerretti D.P., Daniel T.O., Huynh-Do U.;
RT "EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote
RT chemotaxis.";
RL J. Cell Biol. 162:661-671(2003).
RN [14]
RP FUNCTION IN ERK CASCADE ACTIVATION, UBIQUITINATION BY CBL, INTERACTION WITH
RP CBL, MUTAGENESIS OF LYS-651, AUTOPHOSPHORYLATION, IDENTIFICATION OF EFNB1
RP AS LIGAND, AND SUBCELLULAR LOCATION.
RX PubMed=18034775; DOI=10.1111/j.1600-0854.2007.00679.x;
RA Fasen K., Cerretti D.P., Huynh-Do U.;
RT "Ligand binding induces Cbl-dependent EphB1 receptor degradation through
RT the lysosomal pathway.";
RL Traffic 9:251-266(2008).
RN [15]
RP STRUCTURE BY NMR OF 899-984.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the C-terminal SAM-domain of mouse ephrin type-B
RT receptor 1 precursor (EC 2.7.1.112).";
RL Submitted (JUL-2007) to the PDB data bank.
RN [16]
RP STRUCTURE BY NMR OF 434-528.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structures of the FN3 domain of human ephrin type-B receptor 1.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [17]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-18; MET-387; THR-707; VAL-719; GLN-743;
RP THR-912 AND MET-981.
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: 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. Cognate/functional
CC ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During
CC nervous system development, regulates retinal axon guidance redirecting
CC ipsilaterally ventrotemporal retinal ganglion cells axons at the optic
CC chiasm midline. This probably requires repulsive interaction with
CC EFNB2. In the adult nervous system together with EFNB3, regulates
CC chemotaxis, proliferation and polarity of the hippocampus neural
CC progenitors. In addition to its role in axon guidance also plays an
CC important redundant role with other ephrin-B receptors in development
CC and maturation of dendritic spines and synapse formation. May also
CC regulate angiogenesis. More generally, may play a role in targeted cell
CC migration and adhesion. Upon activation by EFNB1 and probably other
CC ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades
CC to regulate cell migration and adhesion respectively. Involved in the
CC maintenance of the pool of satellite cells (muscle stem cells) by
CC promoting their self-renewal and reducing their activation and
CC differentiation (By similarity). {ECO:0000250|UniProtKB:Q8CBF3,
CC ECO:0000269|PubMed:12223469, ECO:0000269|PubMed:12925710,
CC ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:9430661,
CC ECO:0000269|PubMed:9499402}.
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 EPHB6; transphosphorylates EPHB6 to form an active
CC signaling complex. Interacts with PICK1 (By similarity). Interacts
CC (through Tyr-594) with NCK1 (via SH2 domain); activates the JUN cascade
CC to regulate cell adhesion (By similarity). The ligand-activated form
CC interacts (through Tyr-928) with GRB7 and GRB10 (via SH2 domains). The
CC ligand-activated form interacts (residues within the catalytic domain)
CC with GRB2 (via SH2 domain). Interacts with GRB2, SHC1 and SRC;
CC activates the MAPK/ERK cascade to regulate cell migration. Interacts
CC with CBL; regulates receptor degradation through ubiquitination.
CC Interacts with ACP1. {ECO:0000250|UniProtKB:Q8CBF3,
CC ECO:0000269|PubMed:11713248, ECO:0000269|PubMed:12223469,
CC ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:18034775,
CC ECO:0000269|PubMed:8798570, ECO:0000269|PubMed:9430661,
CC ECO:0000269|PubMed:9499402}.
CC -!- INTERACTION:
CC P54762; Q13322: GRB10; NbExp=2; IntAct=EBI-80252, EBI-80275;
CC P54762; P62993: GRB2; NbExp=2; IntAct=EBI-80252, EBI-401755;
CC P54762; Q14451: GRB7; NbExp=4; IntAct=EBI-80252, EBI-970191;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18034775};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:18034775}.
CC Early endosome membrane {ECO:0000269|PubMed:18034775}. Cell projection,
CC dendrite {ECO:0000250|UniProtKB:Q8CBF3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P54762-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P54762-5; Sequence=VSP_056017;
CC Name=3;
CC IsoId=P54762-6; Sequence=VSP_056018, VSP_056019;
CC -!- TISSUE SPECIFICITY: Preferentially expressed in brain.
CC -!- PTM: Phosphorylated. Autophosphorylation is stimulated by the ligand
CC EFNB1. Required for interaction with SH2 domain-containing interactors,
CC for activation of the MAPK/ERK and JUN signaling cascades and for
CC ubiquitination by CBL. {ECO:0000269|PubMed:12223469,
CC ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:8798570}.
CC -!- PTM: Ubiquitinated; (EFNB1)ligand-induced poly- and/or multi-
CC ubiquitination by CBL is regulated by SRC and leads to lysosomal
CC degradation. {ECO:0000269|PubMed:18034775}.
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=AAB94627.1; Type=Miscellaneous discrepancy; Note=wrong intron-exon boundaries.; Evidence={ECO:0000305};
CC Sequence=AAB94628.1; Type=Miscellaneous discrepancy; Note=wrong intron-exon boundaries.; Evidence={ECO:0000305};
CC Sequence=AAD02031.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305};
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DR EMBL; L40636; AAB08520.1; -; mRNA.
DR EMBL; AF037331; AAD02030.1; -; mRNA.
DR EMBL; AF037332; AAD02031.1; ALT_SEQ; mRNA.
DR EMBL; AF037333; AAB94627.1; ALT_SEQ; mRNA.
DR EMBL; AF037334; AAB94628.1; ALT_SEQ; mRNA.
DR EMBL; EU826607; ACF47643.1; -; mRNA.
DR EMBL; AK095305; BAG53024.1; -; mRNA.
DR EMBL; AK291208; BAF83897.1; -; mRNA.
DR EMBL; AC016931; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC016951; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC063918; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073244; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092969; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC111744; AAI11745.1; -; mRNA.
DR CCDS; CCDS46921.1; -. [P54762-1]
DR RefSeq; NP_004432.1; NM_004441.4. [P54762-1]
DR PDB; 2DJS; NMR; -; A=434-528.
DR PDB; 2EAO; NMR; -; A=899-984.
DR PDB; 3ZFX; X-ray; 2.50 A; A/B/C/D/E/F/G/H/I=602-896.
DR PDB; 5MJA; X-ray; 2.14 A; A/B=602-896.
DR PDB; 5MJB; X-ray; 2.23 A; A/B=602-896.
DR PDB; 6UMW; X-ray; 1.98 A; A=602-896.
DR PDB; 7KPL; X-ray; 2.71 A; A=611-889.
DR PDB; 7KPM; X-ray; 1.61 A; A=611-889.
DR PDBsum; 2DJS; -.
DR PDBsum; 2EAO; -.
DR PDBsum; 3ZFX; -.
DR PDBsum; 5MJA; -.
DR PDBsum; 5MJB; -.
DR PDBsum; 6UMW; -.
DR PDBsum; 7KPL; -.
DR PDBsum; 7KPM; -.
DR AlphaFoldDB; P54762; -.
DR SMR; P54762; -.
DR BioGRID; 108361; 19.
DR IntAct; P54762; 25.
DR MINT; P54762; -.
DR STRING; 9606.ENSP00000381097; -.
DR BindingDB; P54762; -.
DR ChEMBL; CHEMBL5072; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P54762; -.
DR GuidetoPHARMACOLOGY; 1830; -.
DR GlyGen; P54762; 4 sites.
DR iPTMnet; P54762; -.
DR PhosphoSitePlus; P54762; -.
DR BioMuta; EPHB1; -.
DR DMDM; 1706663; -.
DR EPD; P54762; -.
DR jPOST; P54762; -.
DR MassIVE; P54762; -.
DR MaxQB; P54762; -.
DR PaxDb; P54762; -.
DR PeptideAtlas; P54762; -.
DR PRIDE; P54762; -.
DR ProteomicsDB; 3673; -.
DR ProteomicsDB; 56716; -. [P54762-1]
DR Antibodypedia; 33398; 589 antibodies from 40 providers.
DR DNASU; 2047; -.
DR Ensembl; ENST00000398015.8; ENSP00000381097.3; ENSG00000154928.19. [P54762-1]
DR Ensembl; ENST00000493838.1; ENSP00000419574.1; ENSG00000154928.19. [P54762-5]
DR GeneID; 2047; -.
DR KEGG; hsa:2047; -.
DR MANE-Select; ENST00000398015.8; ENSP00000381097.3; NM_004441.5; NP_004432.1.
DR UCSC; uc003eqt.4; human. [P54762-1]
DR CTD; 2047; -.
DR DisGeNET; 2047; -.
DR GeneCards; EPHB1; -.
DR HGNC; HGNC:3392; EPHB1.
DR HPA; ENSG00000154928; Tissue enhanced (brain).
DR MalaCards; EPHB1; -.
DR MIM; 600600; gene.
DR neXtProt; NX_P54762; -.
DR OpenTargets; ENSG00000154928; -.
DR PharmGKB; PA27824; -.
DR VEuPathDB; HostDB:ENSG00000154928; -.
DR eggNOG; KOG0196; Eukaryota.
DR GeneTree; ENSGT00940000155297; -.
DR HOGENOM; CLU_000288_141_0_1; -.
DR InParanoid; P54762; -.
DR OMA; MACKACP; -.
DR PhylomeDB; P54762; -.
DR TreeFam; TF315608; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P54762; -.
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; P54762; -.
DR SIGNOR; P54762; -.
DR BioGRID-ORCS; 2047; 6 hits in 1105 CRISPR screens.
DR ChiTaRS; EPHB1; human.
DR EvolutionaryTrace; P54762; -.
DR GeneWiki; EPH_receptor_B1; -.
DR GenomeRNAi; 2047; -.
DR Pharos; P54762; Tchem.
DR PRO; PR:P54762; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P54762; protein.
DR Bgee; ENSG00000154928; Expressed in cortical plate and 137 other tissues.
DR ExpressionAtlas; P54762; baseline and differential.
DR Genevisible; P54762; HS.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0032433; C:filopodium tip; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008046; F:axon guidance receptor activity; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR GO; GO:0048593; P:camera-type eye morphogenesis; IEA:Ensembl.
DR GO; GO:0060326; P:cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0031589; P:cell-substrate adhesion; IDA:UniProtKB.
DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; ISS:UniProtKB.
DR GO; GO:0060996; P:dendritic spine development; ISS:UniProtKB.
DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:UniProtKB.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; ISS:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0030010; P:establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:0021934; P:hindbrain tangential cell migration; IEA:Ensembl.
DR GO; GO:0001771; P:immunological synapse formation; IEA:Ensembl.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:1902725; P:negative regulation of satellite cell differentiation; ISS:UniProtKB.
DR GO; GO:1902723; P:negative regulation of skeletal muscle satellite cell proliferation; ISS:UniProtKB.
DR GO; GO:0061351; P:neural precursor cell proliferation; ISS:UniProtKB.
DR GO; GO:0022008; P:neurogenesis; ISS:UniProtKB.
DR GO; GO:0021631; P:optic nerve morphogenesis; IEA:Ensembl.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:1901214; P:regulation of neuron death; IMP:UniProtKB.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; ISS:UniProtKB.
DR GO; GO:0014719; P:skeletal muscle satellite cell activation; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10476; EphR_LBD_B1; 1.
DR CDD; cd00063; FN3; 2.
DR CDD; cd09551; SAM_EPH-B1; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR034231; EphB1_rcpt_lig-bd.
DR InterPro; IPR042819; EphB1_SAM.
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; 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; ATP-binding; Cell adhesion;
KW Cell membrane; Cell projection; Direct protein sequencing; Endosome;
KW Glycoprotein; Kinase; Membrane; Neurogenesis; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 18..984
FT /note="Ephrin type-B receptor 1"
FT /id="PRO_0000016824"
FT TOPO_DOM 18..540
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 541..563
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 564..984
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 19..201
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 322..432
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 433..528
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 619..882
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 911..975
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT MOTIF 982..984
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 744
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 625..633
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 651
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 600
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P54753"
FT MOD_RES 928
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 426
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..439
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056017"
FT VAR_SEQ 158..242
FT /note="VNTEVRSFGPLTRNGFYLAFQDYGACMSLLSVRVFFKKCPSIVQNFAVFPET
FT MTGAESTSLVIARGTCIPNAEEVDVPIKLYCNG -> LALQGHSRPARKLKAAPTAPPT
FT AAPLQRRLPSAPVGPVITERTLTLQKWHALASHQVPAMLSPSSMRRPSFWSGTLQGRQV
FT GGMM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_056018"
FT VAR_SEQ 243..984
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_056019"
FT VARIANT 18
FT /note="M -> V (in dbSNP:rs55650774)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042165"
FT VARIANT 87
FT /note="T -> S (in dbSNP:rs1042794)"
FT /id="VAR_011801"
FT VARIANT 152
FT /note="G -> R (in dbSNP:rs1042793)"
FT /id="VAR_011802"
FT VARIANT 367
FT /note="R -> G (in dbSNP:rs1042789)"
FT /id="VAR_011803"
FT VARIANT 387
FT /note="T -> M (in dbSNP:rs56396912)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042166"
FT VARIANT 485
FT /note="R -> S (in dbSNP:rs1042788)"
FT /id="VAR_011804"
FT VARIANT 707
FT /note="S -> T (in an ovarian undifferentiated carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042167"
FT VARIANT 719
FT /note="I -> V (in a gastric adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042168"
FT VARIANT 743
FT /note="R -> Q (in a gastric adenocarcinoma sample; somatic
FT mutation; dbSNP:rs1338928289)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042169"
FT VARIANT 847
FT /note="M -> T (in dbSNP:rs1042785)"
FT /id="VAR_011805"
FT VARIANT 912
FT /note="A -> T (in dbSNP:rs56345346)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042170"
FT VARIANT 973
FT /note="R -> W (in dbSNP:rs1042784)"
FT /evidence="ECO:0000269|PubMed:9430661"
FT /id="VAR_058479"
FT VARIANT 981
FT /note="T -> M (in dbSNP:rs56186270)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042171"
FT MUTAGEN 594
FT /note="Y->F: Loss of interaction with NCK1."
FT /evidence="ECO:0000269|PubMed:9430661"
FT MUTAGEN 600
FT /note="Y->F: Loss of interaction with SHC1 and SRC."
FT /evidence="ECO:0000269|PubMed:12925710"
FT MUTAGEN 651
FT /note="K->R: Kinase-dead mutant. Unable to
FT autophosphorylate, to interact with SH2 domain-containing
FT interactors, to activate the MAPK/ERK and JUN signaling
FT cascades. Not ubiquitinated by CBL."
FT /evidence="ECO:0000269|PubMed:18034775,
FT ECO:0000269|PubMed:9430661"
FT MUTAGEN 778
FT /note="Y->F: Loss of interaction with SHC1."
FT /evidence="ECO:0000269|PubMed:12925710"
FT MUTAGEN 928
FT /note="Y->F: Disrupts binding with the GRB10 SH2 domain,
FT providing evidence for phosphorylation. Disrupts
FT interaction with GRB7 and ACP1."
FT /evidence="ECO:0000269|PubMed:12223469,
FT ECO:0000269|PubMed:8798570, ECO:0000269|PubMed:9499402"
FT CONFLICT 12
FT /note="A -> E (in Ref. 2; AAD02030/AAB94627/AAB94628)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="S -> I (in Ref. 2; AAD02030/AAD02031/AAB94627/
FT AAB94628)"
FT /evidence="ECO:0000305"
FT CONFLICT 274
FT /note="T -> R (in Ref. 2; AAD02030/AAD02031/AAB94627/
FT AAB94628)"
FT /evidence="ECO:0000305"
FT CONFLICT 336
FT /note="T -> S (in Ref. 2; AAD02030/AAD02031/AAB94627/
FT AAB94628)"
FT /evidence="ECO:0000305"
FT CONFLICT 752
FT /note="V -> L (in Ref. 6; AAI11745)"
FT /evidence="ECO:0000305"
FT CONFLICT 813
FT /note="V -> H (in Ref. 2; AAD02030/AAB94627)"
FT /evidence="ECO:0000305"
FT CONFLICT 819
FT /note="S -> Y (in Ref. 2; AAD02030/AAB94627)"
FT /evidence="ECO:0000305"
FT CONFLICT 881
FT /note="M -> I (in Ref. 4; BAF83897)"
FT /evidence="ECO:0000305"
FT CONFLICT 903
FT /note="L -> H (in Ref. 4; BAF83897)"
FT /evidence="ECO:0000305"
FT STRAND 441..445
FT /evidence="ECO:0007829|PDB:2DJS"
FT STRAND 447..453
FT /evidence="ECO:0007829|PDB:2DJS"
FT STRAND 464..473
FT /evidence="ECO:0007829|PDB:2DJS"
FT STRAND 482..495
FT /evidence="ECO:0007829|PDB:2DJS"
FT STRAND 501..512
FT /evidence="ECO:0007829|PDB:2DJS"
FT STRAND 514..517
FT /evidence="ECO:0007829|PDB:2DJS"
FT STRAND 521..524
FT /evidence="ECO:0007829|PDB:2DJS"
FT HELIX 616..618
FT /evidence="ECO:0007829|PDB:7KPM"
FT STRAND 619..627
FT /evidence="ECO:0007829|PDB:7KPM"
FT STRAND 632..638
FT /evidence="ECO:0007829|PDB:7KPM"
FT STRAND 646..652
FT /evidence="ECO:0007829|PDB:7KPM"
FT HELIX 659..673
FT /evidence="ECO:0007829|PDB:7KPM"
FT STRAND 683..687
FT /evidence="ECO:0007829|PDB:7KPM"
FT STRAND 689..692
FT /evidence="ECO:0007829|PDB:7KPM"
FT STRAND 694..698
FT /evidence="ECO:0007829|PDB:7KPM"
FT HELIX 705..710
FT /evidence="ECO:0007829|PDB:7KPM"
FT TURN 711..714
FT /evidence="ECO:0007829|PDB:7KPM"
FT HELIX 718..737
FT /evidence="ECO:0007829|PDB:7KPM"
FT HELIX 747..749
FT /evidence="ECO:0007829|PDB:7KPM"
FT STRAND 750..752
FT /evidence="ECO:0007829|PDB:7KPM"
FT STRAND 758..760
FT /evidence="ECO:0007829|PDB:7KPM"
FT STRAND 783..786
FT /evidence="ECO:0007829|PDB:5MJB"
FT HELIX 788..790
FT /evidence="ECO:0007829|PDB:7KPM"
FT HELIX 793..798
FT /evidence="ECO:0007829|PDB:7KPM"
FT HELIX 803..818
FT /evidence="ECO:0007829|PDB:7KPM"
FT TURN 824..827
FT /evidence="ECO:0007829|PDB:7KPM"
FT HELIX 830..838
FT /evidence="ECO:0007829|PDB:7KPM"
FT HELIX 851..860
FT /evidence="ECO:0007829|PDB:7KPM"
FT HELIX 865..867
FT /evidence="ECO:0007829|PDB:7KPM"
FT HELIX 871..883
FT /evidence="ECO:0007829|PDB:7KPM"
FT HELIX 885..887
FT /evidence="ECO:0007829|PDB:7KPM"
FT STRAND 889..891
FT /evidence="ECO:0007829|PDB:3ZFX"
FT HELIX 916..921
FT /evidence="ECO:0007829|PDB:2EAO"
FT TURN 922..924
FT /evidence="ECO:0007829|PDB:2EAO"
FT HELIX 926..928
FT /evidence="ECO:0007829|PDB:2EAO"
FT HELIX 929..935
FT /evidence="ECO:0007829|PDB:2EAO"
FT HELIX 940..943
FT /evidence="ECO:0007829|PDB:2EAO"
FT HELIX 948..954
FT /evidence="ECO:0007829|PDB:2EAO"
FT HELIX 959..975
FT /evidence="ECO:0007829|PDB:2EAO"
SQ SEQUENCE 984 AA; 109885 MW; 8044160E24E93A92 CRC64;
MALDYLLLLL LASAVAAMEE TLMDTRTATA ELGWTANPAS GWEEVSGYDE NLNTIRTYQV
CNVFEPNQNN WLLTTFINRR GAHRIYTEMR FTVRDCSSLP NVPGSCKETF NLYYYETDSV
IATKKSAFWS EAPYLKVDTI AADESFSQVD FGGRLMKVNT EVRSFGPLTR NGFYLAFQDY
GACMSLLSVR VFFKKCPSIV QNFAVFPETM TGAESTSLVI ARGTCIPNAE EVDVPIKLYC
NGDGEWMVPI GRCTCKPGYE PENSVACKAC PAGTFKASQE AEGCSHCPSN SRSPAEASPI
CTCRTGYYRA DFDPPEVACT SVPSGPRNVI SIVNETSIIL EWHPPRETGG RDDVTYNIIC
KKCRADRRSC SRCDDNVEFV PRQLGLTECR VSISSLWAHT PYTFDIQAIN GVSSKSPFPP
QHVSVNITTN QAAPSTVPIM HQVSATMRSI TLSWPQPEQP NGIILDYEIR YYEKEHNEFN
SSMARSQTNT ARIDGLRPGM VYVVQVRART VAGYGKFSGK MCFQTLTDDD YKSELREQLP
LIAGSAAAGV VFVVSLVAIS IVCSRKRAYS KEAVYSDKLQ HYSTGRGSPG MKIYIDPFTY
EDPNEAVREF AKEIDVSFVK IEEVIGAGEF GEVYKGRLKL PGKREIYVAI KTLKAGYSEK
QRRDFLSEAS IMGQFDHPNI IRLEGVVTKS RPVMIITEFM ENGALDSFLR QNDGQFTVIQ
LVGMLRGIAA GMKYLAEMNY VHRDLAARNI LVNSNLVCKV SDFGLSRYLQ DDTSDPTYTS
SLGGKIPVRW TAPEAIAYRK FTSASDVWSY GIVMWEVMSF GERPYWDMSN QDVINAIEQD
YRLPPPMDCP AALHQLMLDC WQKDRNSRPR FAEIVNTLDK MIRNPASLKT VATITAVPSQ
PLLDRSIPDF TAFTTVDDWL SAIKMVQYRD SFLTAGFTSL QLVTQMTSED LLRIGITLAG
HQKKILNSIH SMRVQISQSP TAMA
