EPHB1_RAT
ID EPHB1_RAT Reviewed; 984 AA.
AC P09759;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 2.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Ephrin type-B receptor 1;
DE EC=2.7.10.1;
DE AltName: Full=ELK;
DE AltName: Full=Tyrosine-protein kinase receptor EPH-2;
DE Flags: Precursor;
GN Name=Ephb1; Synonyms=Elk, Epth2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AUTOPHOSPHORYLATION, AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=2017163; DOI=10.1128/mcb.11.5.2496-2502.1991;
RA Lhotak V., Greer P., Letwin K., Pawson T.;
RT "Characterization of elk, a brain-specific receptor tyrosine kinase.";
RL Mol. Cell. Biol. 11:2496-2502(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 605-984.
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=2485255;
RA Letwin K., Yee S.P., Pawson T.;
RT "Novel protein-tyrosine kinase cDNAs related to fps/fes and eph cloned
RT using anti-phosphotyrosine antibody.";
RL Oncogene 3:621-627(1988).
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 (By similarity).
CC Involved in the maintenance of the pool of satellite cells (muscle stem
CC cells) by promoting their self-renewal and reducing their activation
CC and differentiation (By similarity). {ECO:0000250|UniProtKB:P54762,
CC ECO:0000250|UniProtKB:Q8CBF3}.
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. Interacts with EPHB6;
CC transphosphorylates EPHB6 to form an active signaling complex.
CC Interacts with PICK1. Interacts (through Tyr-594) with NCK1 (via SH2
CC domain); activates the JUN cascade to regulate cell adhesion. The
CC ligand-activated form interacts (through Tyr-928) with GRB7 and GRB10
CC (via SH2 domains). The ligand-activated form interacts (residues within
CC the catalytic domain) with GRB2 (via SH2 domain). Interacts with GRB2,
CC SHC1 and SRC; activates the MAPK/ERK cascade to regulate cell
CC migration. Interacts with CBL; regulates receptor degradation through
CC ubiquitination. Interacts with ACP1 (By similarity).
CC {ECO:0000250|UniProtKB:P54762, ECO:0000250|UniProtKB:Q8CBF3}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P54762};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P54762}.
CC Early endosome membrane {ECO:0000250|UniProtKB:P54762}. Cell
CC projection, dendrite {ECO:0000250|UniProtKB:Q8CBF3}.
CC -!- TISSUE SPECIFICITY: Restricted to brain and testes.
CC {ECO:0000269|PubMed:2017163}.
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 (By similarity). {ECO:0000250|UniProtKB:P54762}.
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:0000250|UniProtKB:P54762,
CC ECO:0000250|UniProtKB:Q8CBF3}.
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; M59814; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; X13411; CAA31777.1; -; mRNA.
DR PIR; A39753; A39753.
DR RefSeq; NP_001097998.1; NM_001104528.1.
DR RefSeq; XP_017450939.1; XM_017595450.1.
DR AlphaFoldDB; P09759; -.
DR SMR; P09759; -.
DR BioGRID; 246515; 2.
DR CORUM; P09759; -.
DR DIP; DIP-138N; -.
DR STRING; 10116.ENSRNOP00000010634; -.
DR BindingDB; P09759; -.
DR ChEMBL; CHEMBL4739675; -.
DR GuidetoPHARMACOLOGY; 1830; -.
DR GlyGen; P09759; 3 sites.
DR iPTMnet; P09759; -.
DR PhosphoSitePlus; P09759; -.
DR SwissPalm; P09759; -.
DR PaxDb; P09759; -.
DR PRIDE; P09759; -.
DR Ensembl; ENSRNOT00000010634; ENSRNOP00000010634; ENSRNOG00000007865.
DR GeneID; 24338; -.
DR KEGG; rno:24338; -.
DR UCSC; RGD:2556; rat.
DR CTD; 2047; -.
DR RGD; 2556; Ephb1.
DR eggNOG; KOG0196; Eukaryota.
DR GeneTree; ENSGT00940000155297; -.
DR HOGENOM; CLU_000288_141_4_1; -.
DR InParanoid; P09759; -.
DR OMA; MACKACP; -.
DR OrthoDB; 933071at2759; -.
DR PhylomeDB; P09759; -.
DR TreeFam; TF315608; -.
DR BRENDA; 2.7.10.1; 5301.
DR Reactome; R-RNO-2682334; EPH-Ephrin signaling.
DR Reactome; R-RNO-3928662; EPHB-mediated forward signaling.
DR Reactome; R-RNO-3928664; Ephrin signaling.
DR Reactome; R-RNO-3928665; EPH-ephrin mediated repulsion of cells.
DR PRO; PR:P09759; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000007865; Expressed in brain and 17 other tissues.
DR Genevisible; P09759; RN.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0032433; C:filopodium tip; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
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; ISO:RGD.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:RGD.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR GO; GO:0048593; P:camera-type eye morphogenesis; ISO:RGD.
DR GO; GO:0060326; P:cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0031589; P:cell-substrate adhesion; ISS:UniProtKB.
DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; ISS:UniProtKB.
DR GO; GO:0021545; P:cranial nerve development; ISO:RGD.
DR GO; GO:0060996; P:dendritic spine development; IGI:MGI.
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; ISS:UniProtKB.
DR GO; GO:0030010; P:establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:0021934; P:hindbrain tangential cell migration; IMP:RGD.
DR GO; GO:0001771; P:immunological synapse formation; IGI:MGI.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:RGD.
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; ISO:RGD.
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:RGD.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0046328; P:regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:1901214; P:regulation of neuron death; ISO:RGD.
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 ATP-binding; Cell adhesion; Cell membrane; Cell projection; 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:0000255"
FT CHAIN 18..984
FT /note="Ephrin type-B receptor 1"
FT /id="PRO_0000016825"
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:0000255|PROSITE-ProRule:PRU00159"
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"
SQ SEQUENCE 984 AA; 109883 MW; 521EAC240D8FB91A CRC64;
MALDCLLLFL LASAVAAMEE TLMDTRTATA ELGWTANPAS GWEEVSGYDE NLNTIRTYQV
CNVFEPNQNN WLLTTFINRR GAHRIYTEMR FTVRDCSSLP NVPGSCKETF NLYYYETDSV
IATKKSAFWS EAPYLKVDTI AADESFSQVD FGGRLMKVNT EVRSFGPLTR NGFYLAFQDY
GACMSLLSVR VFFKKCPSIV QNFAVFPETM TGAESTSLVI ARGTCIPNAE EVDVPIKLYC
NGDGEWMVPI GRCTCKAGYE PENSVACKAC PAGTFKASQE AEGCSHCPSN SRSPSEASPI
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 GMKYLSEMNY VHRDLAARNI LVNSNLVCKV SDFGLSRYLQ DDTSDPTYTS
SLGGKIPVRW TAPEAIAYRK FTSASDVWSY GIVMWEVMSF GERPYWDMSN QDVINAIEQD
YRLPPPMDCP AALHQLMLDC WQKDRNSRPR FAEIVNTLDK MIRNPASLKT VATITAVPSQ
PLLDRSIPDF TAFTTVDDWL SAIKMVQYRD SFLTAGFTSL QLVTQMTSED LLRIGVTLAG
HQKKILSSIH SMRVQMNQSP SVMA
