EPA4A_DANRE
ID EPA4A_DANRE Reviewed; 292 AA.
AC O13148;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Ephrin type-A receptor 4a;
DE EC=2.7.10.1;
DE AltName: Full=EPH-like kinase 2;
DE AltName: Full=Tyrosine-protein kinase receptor ZEK2;
DE Flags: Fragment;
GN Name=epha4a; Synonyms=ek2, zek2;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9186052;
RX DOI=10.1002/(sici)1097-0177(199706)209:2<166::aid-aja3>3.0.co;2-g;
RA Bovenkamp D.E., Greer P.;
RT "Novel Eph-family receptor tyrosine kinase is widely expressed in the
RT developing zebrafish nervous system.";
RL Dev. Dyn. 209:166-181(1997).
CC -!- FUNCTION: Receptor tyrosine kinase which binds membrane-bound ephrin
CC family ligands residing on adjacent cells, leading to contact-dependent
CC bidirectional signaling into neighboring cells. The signaling pathway
CC downstream of the receptor is referred to as forward signaling while
CC the signaling pathway downstream of the ephrin ligand is referred to as
CC reverse signaling. Highly promiscuous, it has the unique property among
CC Eph receptors to bind and to be physiologically activated by both GPI-
CC anchored ephrin-A and transmembrane ephrin-B ligands including efna1
CC and efnb3. Upon activation by ephrin ligands, modulates cell morphology
CC and integrin-dependent cell adhesion through regulation of the Rac, Rap
CC and Rho GTPases activity. Plays an important role in the development of
CC the nervous system controlling different steps of axonal guidance
CC including the establishment of the corticospinal projections (By
CC similarity). {ECO:0000250}.
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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Early endosome {ECO:0000250}.
CC Note=Clustered upon activation and targeted to early endosome.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed in the developing nervous system.
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; U89380; AAC60222.1; -; mRNA.
DR AlphaFoldDB; O13148; -.
DR SMR; O13148; -.
DR STRING; 7955.ENSDARP00000123962; -.
DR PaxDb; O13148; -.
DR PeptideAtlas; O13148; -.
DR ZFIN; ZDB-GENE-001207-7; epha4a.
DR eggNOG; KOG0196; Eukaryota.
DR InParanoid; O13148; -.
DR Reactome; R-DRE-2682334; EPH-Ephrin signaling.
DR Reactome; R-DRE-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-DRE-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-DRE-9013149; RAC1 GTPase cycle.
DR Reactome; R-DRE-9013404; RAC2 GTPase cycle.
DR Reactome; R-DRE-9013408; RHOG GTPase cycle.
DR Reactome; R-DRE-9013420; RHOU GTPase cycle.
DR Reactome; R-DRE-9013423; RAC3 GTPase cycle.
DR Reactome; R-DRE-9013424; RHOV GTPase cycle.
DR Reactome; R-DRE-9696264; RND3 GTPase cycle.
DR Reactome; R-DRE-9696270; RND2 GTPase cycle.
DR Reactome; R-DRE-9696273; RND1 GTPase cycle.
DR SignaLink; O13148; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
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:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0009952; P:anterior/posterior pattern specification; IMP:ZFIN.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0009988; P:cell-cell recognition; IMP:ZFIN.
DR GO; GO:0030900; P:forebrain development; IMP:ZFIN.
DR GO; GO:0030517; P:negative regulation of axon extension; IGI:ZFIN.
DR GO; GO:0048685; P:negative regulation of collateral sprouting of intact axon in response to injury; IGI:ZFIN.
DR GO; GO:0003404; P:optic vesicle morphogenesis; IGI:ZFIN.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0031641; P:regulation of myelination; IMP:ZFIN.
DR GO; GO:0021654; P:rhombomere boundary formation; IMP:ZFIN.
DR GO; GO:0061053; P:somite development; IGI:ZFIN.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Endosome; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN <1..>292
FT /note="Ephrin type-A receptor 4a"
FT /id="PRO_0000160272"
FT DOMAIN <1..265
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 120
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 1..9
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 27
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 153
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT NON_TER 1
FT NON_TER 292
SQ SEQUENCE 292 AA; 33045 MW; 923879877EF13879 CRC64;
IGIGEFGEVC SGRLKMPGKR EICVAIKTLK AGYTDKQRRD FLSEASIMGQ FDHPNIIRLE
GVVTKCKPVM IITEYMENGS LDAFLRKNDG RFTVIQLVGI LRGIASGMKY LSDMSYVHRD
LAARNILVNS NLVCKVSDFG MSRVLEEDPD AAYTTREITG TYQSQGGKIP IRWTAPEAIT
YRKFTSASDV WSYGIVMWEV MSYGERPYWD MSNQDVIKAI EEGYRLPPPM DCPVSLHQLM
LDCWQKERAE RPKFSQIVNM LDKLIRNPNS LKRTGGEIAR PNTTLLEPSS PE
