EPHA4_CHICK
ID EPHA4_CHICK Reviewed; 986 AA.
AC Q07496; Q90772;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Ephrin type-A receptor 4;
DE EC=2.7.10.1;
DE AltName: Full=EPH-like kinase 8;
DE Short=EK8;
DE Short=cEK8;
DE Flags: Precursor;
GN Name=EPHA4; Synonyms=CEK8;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spinal cord;
RX PubMed=8808406; DOI=10.1016/0925-4773(95)00461-0;
RA Ohta K., Nakamura M., Hirokawa K., Tanaka S., Iwama A., Suda T., Ando M.,
RA Tanaka H.;
RT "The receptor tyrosine kinase, Cek8, is transiently expressed on subtypes
RT of motoneurons in the spinal cord during development.";
RL Mech. Dev. 54:59-69(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 138-986.
RC TISSUE=Embryo;
RX PubMed=8510926;
RA Sajjadi F.G., Pasquale E.B.;
RT "Five novel avian Eph-related tyrosine kinases are differentially
RT expressed.";
RL Oncogene 8:1807-1813(1993).
RN [3]
RP INTERACTION WITH SIPA1L1.
RX PubMed=18094260; DOI=10.1523/jneurosci.2746-07.2007;
RA Richter M., Murai K.K., Bourgin C., Pak D.T., Pasquale E.B.;
RT "The EphA4 receptor regulates neuronal morphology through SPAR-mediated
RT inactivation of Rap GTPases.";
RL J. Neurosci. 27:14205-14215(2007).
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 -!- SUBUNIT: Interacts with the src family kinase, p59-Fyn, through the
CC major phosphorylation site at position Tyr-602 (By similarity).
CC Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls
CC neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and
CC RAP2 (RAP2A, RAP2B or RAP2C) GTPases. {ECO:0000250,
CC ECO:0000269|PubMed:18094260}.
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: Expressed at high levels in brain, with expression
CC also detected in the kidney, lung, muscle and thymus.
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; D38174; BAA07373.1; -; mRNA.
DR EMBL; Z19059; CAA79509.1; -; mRNA.
DR PIR; I50617; I50617.
DR RefSeq; NP_990112.1; NM_204781.1.
DR AlphaFoldDB; Q07496; -.
DR SMR; Q07496; -.
DR BioGRID; 675840; 1.
DR STRING; 9031.ENSGALP00000008426; -.
DR PaxDb; Q07496; -.
DR Ensembl; ENSGALT00000008440; ENSGALP00000008426; ENSGALG00000005256.
DR GeneID; 395559; -.
DR KEGG; gga:395559; -.
DR CTD; 2043; -.
DR VEuPathDB; HostDB:geneid_395559; -.
DR eggNOG; KOG0196; Eukaryota.
DR GeneTree; ENSGT00940000156948; -.
DR HOGENOM; CLU_000288_141_1_1; -.
DR InParanoid; Q07496; -.
DR OMA; TENSRPN; -.
DR PhylomeDB; Q07496; -.
DR TreeFam; TF315608; -.
DR BRENDA; 2.7.10.1; 1306.
DR PRO; PR:Q07496; -.
DR Proteomes; UP000000539; Chromosome 9.
DR Bgee; ENSGALG00000005256; Expressed in testis and 14 other tissues.
DR ExpressionAtlas; Q07496; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS: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:0097161; F:DH domain binding; ISS:UniProtKB.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
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:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0097155; P:fasciculation of sensory neuron axon; ISS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:2001108; P:positive regulation of Rho guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0035282; P:segmentation; NAS:AgBase.
DR GO; GO:0001756; P:somitogenesis; NAS:AgBase.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10482; EphR_LBD_A4; 1.
DR CDD; cd00063; FN3; 2.
DR CDD; cd09545; SAM_EPH-A4; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR034270; EphA4_rcpt_lig-bd.
DR InterPro; IPR030602; EphA4_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; 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; 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; SM00220; S_TKc; 1.
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; Developmental protein; Endosome;
KW Glycoprotein; Kinase; Membrane; Neurogenesis; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..986
FT /note="Ephrin type-A receptor 4"
FT /id="PRO_0000016809"
FT TOPO_DOM 20..547
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 548..569
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 570..986
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..209
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 328..439
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 440..537
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 621..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 984..986
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 746
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 627..635
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 653
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 596
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 602
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 779
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 928
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 138
FT /note="R -> G (in Ref. 2; CAA79509)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="S -> T (in Ref. 2; CAA79509)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 986 AA; 109483 MW; BD88C2A5BD840A0F CRC64;
MAGVPVGALL PLLVGVCGAV TGSRVYPANE VTLLDSRSVQ GELGWIASPL EGGWEEVSIM
DEKNTPIRTY QVCNVMEPSQ NNWLRTDWIP REGAQRVYIE IKFTLRDCNS LPGVMGTCKE
TFNLYYYESN NDKERFIRES QFAKIDTIAA DESFTQVDIG DRIMKLNTEV RDVGPLSKKG
FYLAFQDVGA CIALVSVRVF YKKCPLTVRN LAQFPDTITG ADTSSLVEVR GSCVNNSEEK
DVPKMYCGAD GEWLVPIGNC LCNAGYEERN GECQACKIGY YKALSTDVAC AKCPPHSYSI
WEGSTSCTCD RGFFRAENDA ASMPCTRPPS APQNLISNVN ETSVNLEWSA PQNKGGRDDI
SYNVVCKRCG AGEPSHCRSC GSGVHFSPQQ NGLKTTKVSI TDLLAHTNYT FEVWAVNGVS
KHNPSQDQAV SVTVTTNQAA PSPIALIQAK EITRHSVALA WLEPDRPNGV ILEYEVKYYE
KDQNERSYRI VKTASRNTDI KGLNPLTSYV FHVRARTAAG YGDFSGPFEF TTNTVPSPII
GDGTNPTVLL VSVAGSVVLV VILIAAFVIS RRRSKYSKAK QEADEEKHLN QGVRTYVDPF
TYEDPNQAVR EFAKEIDASC IKIEKVIGVG EFGEVCSGRL KVPGKREICV AIKTLKAGYT
DKQRRDFLSE ASIMGQFDHP NIIHLEGVVT KCKPVMIITE YMENGSLDAF LRKNDGRFTV
IQLVGMLRGI GSGMKYLSDM SYVHRDLAAR NILVNSNLVC KVSDFGMSRV LEDDPEAAYT
TRGGKIPIRW TAPEAIAYRK FTSASDVWSY GIVMWEVMSY GERPYWDMSN QDVIKAIEEG
YRLPPPMDCP IALHQLMLDC WQKERSDRPK FGQIVNMLDK LIRNPNSLKR TGSESSRPST
ALLDPSSPEF SAVVSVSDWL QAIKMERYKD NFTAAGYTTL EAVVHMNQDD LARIGITAIT
HQNKILSSVQ AMRSQMQQMH GRMVPV
