ID EPHA3_DANRE Reviewed; 981 AA.
AC O13146;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 27-MAR-2024, entry version 176.
DE RecName: Full=Ephrin type-A receptor 3;
DE EC=2.7.10.1;
DE AltName: Full=EPH-like kinase 1;
DE AltName: Full=Tyrosine-protein kinase receptor ZEK1;
DE Flags: Precursor;
GN Name=epha3; Synonyms=ek1, zek1;
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 promiscuously membrane-
CC bound ephrin family ligands residing on adjacent cells, leading to
CC contact-dependent bidirectional signaling into neighboring cells. The
CC signaling pathway downstream of the receptor is referred to as forward
CC signaling while the signaling pathway downstream of the ephrin ligand
CC is referred to as reverse signaling. Highly promiscuous for ephrin-A
CC ligands it binds preferentially efna5. Upon activation by efna5
CC regulates cell-cell adhesion, cytoskeletal organization and cell
CC migration. Plays a role in cardiac cells migration and differentiation
CC probably through activation by efna1. Involved in the retinotectal
CC mapping of neurons. May also control the segregation but not the
CC guidance of motor and sensory axons during neuromuscular circuit
CC development (By 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: 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 {ECO:0000250}.
CC -!- INTERACTION:
CC O13146; Q90YC5: D160; NbExp=2; IntAct=EBI-42473062, EBI-42473207;
CC O13146; P79727: efna2; NbExp=2; IntAct=EBI-42473062, EBI-42473106;
CC O13146; P79728: efna5b; NbExp=2; IntAct=EBI-42473062, EBI-42473236;
CC O13146; O73874: efnb2a; NbExp=2; IntAct=EBI-42473062, EBI-42473274;
CC O13146; Q90Z31: efnb3; NbExp=2; IntAct=EBI-42473062, EBI-42477337;
CC O13146; A0A8M1NF77: zgc:158671; NbExp=2; IntAct=EBI-42473062, EBI-42477359;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P29320};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Widely expressed in the developing zebrafish
CC nervous system.
CC -!- PTM: Autophosphorylates upon activation by efna5. {ECO:0000250}.
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; U89295; AAC60220.1; -; mRNA.
DR RefSeq; NP_571170.1; NM_131095.1.
DR AlphaFoldDB; O13146; -.
DR SMR; O13146; -.
DR IntAct; O13146; 6.
DR STRING; 7955.ENSDARP00000096552; -.
DR GlyCosmos; O13146; 4 sites, No reported glycans.
DR PaxDb; 7955-ENSDARP00000096552; -.
DR GeneID; 30311; -.
DR KEGG; dre:30311; -.
DR AGR; ZFIN:ZDB-GENE-990415-58; -.
DR CTD; 30311; -.
DR ZFIN; ZDB-GENE-990415-58; ek1.
DR eggNOG; KOG0196; Eukaryota.
DR InParanoid; O13146; -.
DR OrthoDB; 1614410at2759; -.
DR PhylomeDB; O13146; -.
DR BRENDA; 2.7.10.1; 928.
DR PRO; PR:O13146; -.
DR Proteomes; UP000000437; Alternate scaffold 24.
DR Proteomes; UP000000437; Chromosome 24.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0097156; P:fasciculation of motor neuron axon; ISS:UniProtKB.
DR GO; GO:0097155; P:fasciculation of sensory neuron axon; ISS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10473; EphR_LBD_A; 1.
DR CDD; cd00063; FN3; 2.
DR CDD; cd05066; PTKc_EphR_A; 1.
DR CDD; cd09488; SAM_EPH-R; 1.
DR Gene3D; 2.60.40.1770; ephrin a2 ectodomain; 1.
DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR Gene3D; 2.10.50.10; Tumor Necrosis Factor Receptor, subunit A, domain 2; 1.
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; 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 PANTHER; PTHR46877; EPH RECEPTOR A5; 1.
DR PANTHER; PTHR46877:SF8; RECEPTOR PROTEIN-TYROSINE KINASE; 1.
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; PR00014; FNTYPEIII.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00615; EPH_lbd; 1.
DR SMART; SM01411; Ephrin_rec_like; 1.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49265; Fibronectin type III; 1.
DR SUPFAM; SSF49785; Galactose-binding domain-like; 1.
DR SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR SUPFAM; SSF47769; SAM/Pointed domain; 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 membrane; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..20
FT /evidence="ECO:0000250"
FT CHAIN 21..981
FT /note="Ephrin type-A receptor 3"
FT /id="PRO_0000016806"
FT TOPO_DOM 21..545
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 546..566
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 567..981
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 29..210
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 328..441
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 442..533
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 626..887
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 910..974
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT MOTIF 979..981
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 751
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 633..638
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 658
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 705..711
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 755..756
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 601
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 607
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 706
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 784
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 927
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 485
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 141
FT /note="S -> N"
SQ SEQUENCE 981 AA; 109655 MW; F0B3F5218965E2C6 CRC64;
MALFRIYSFL APFHILVLCQ ALRNYPDNEV TLLDSMSAPG DLGWEAYPSE GWEEISVMDE
RNIPMRTYQV CNVMEANQNN WLRTGLIQRE GAQRVYVEIK FTLRDCNSLP GVPGTCKETF
NVYYHESNNA VAAPLRHIRE SQYIKIDTIA ADESFTQTDV GDRVMKLNTE VRDISGLSKR
GLYLAFQDLG ACIALVSVRV FYKRCPLAVL NLARFPDTVT GGDSALVEVR GTCVEDAEEL
EGPRMFCSAD GGWLVPIGRC VCRPGFEEVD GHCQPCRSGF YKASAMDAYC VKCPPHSYSH
QDKASECVCE RGFYRAESDP RSMACTRPPS APGNPISMVN ETAVTLEWSP PRDSGGRGDV
SYSVHCRKCS GETGASERCV PCGSGAHFNP RQFGLTHPRV LVTELQPHTN YTFSVEALNG
VSDLSPSPRQ LVSVNVTTSQ TVSVILKERK GTDSVTLAWQ GPEPVDGTVV EYEVTYYEKN
QQDQNYTVLK TKSNSMTVDG LKPGTTYIFR VRARTDGGYG NYKGEIELET SHEDMLAVGD
PNQQTILAIS VAGGAVLLVL LVACFIVSGR RCGYIKAKQD PEEEKMQFQH GRVKLPETRT
YIHPHTYEDP NQAVRDFAKE IEVSNIRIER VIGAGEFGEV CSGRLRLPSK REIQVAIKSL
KAGYSEHQRR DFLSEASIMG QFDHPNIIRL EGVVTRCKPV MIVTEYMENG SLDTFLKKHD
GQFTVIQLLG MLRGIAAGMQ YLSEMNYVHR DLAARNILVN RNLVCKVSDF GLSRVLEDDP
EAAYTTRGGK IPIRWTAPEA ITYRKFTSAS DVWSYGIVMW EVISYGERPY WEMSNQDVIK
AVDEGYRLPA PMDCPVVLHQ LMLDCWEKNR SDRPKFGQIV NTLDRLIRNP SSLKQLANSA
VWEDPVTPEA AVNTVEDWLD LIKMGQYKEH FSSAGYVTLD SVLYVSSSEL DKMGVELAGH
QKKILSSIQC LQAHHGTQVQ V
//
