ID EPHA3_RAT Reviewed; 984 AA.
AC O08680;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 08-NOV-2023, entry version 177.
DE RecName: Full=Ephrin type-A receptor 3;
DE EC=2.7.10.1;
DE AltName: Full=EPH-like kinase 4;
DE Short=EK4;
DE Short=rEK4;
DE AltName: Full=Tyrosine-protein kinase TYRO4;
DE Flags: Precursor;
GN Name=Epha3; Synonyms=Rek4, Tyro4;
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].
RC STRAIN=Sprague-Dawley;
RX PubMed=9458884; DOI=10.1152/ajpheart.1998.274.1.h331;
RA Li Y.Y., McTiernan C.F., Feldman A.M.;
RT "IL-1 beta alters the expression of the receptor tyrosine kinase gene r-
RT EphA3 in neonatal rat cardiomyocytes.";
RL Am. J. Physiol. 274:H331-H341(1998).
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 and regulates the formation of the atrioventricular canal and septum
CC during development probably through activation by EFNA1. Involved in
CC the retinotectal mapping of neurons. May also control the segregation
CC but not the guidance of motor and sensory axons during neuromuscular
CC circuit 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. Forms a ternary
CC EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain
CC shedding by ADAM10 which regulates the EFNA5-EPHA3 complex
CC internalization and function. Interacts (phosphorylated) with PTPN1;
CC dephosphorylates EPHA3 and may regulate its trafficking and function.
CC Interacts (phosphorylated) with CRK; mediates EFNA5-EPHA3 signaling
CC through RHOA GTPase activation. Interacts with NCK1 (via SH2 domain);
CC mediates EFNA5-EPHA3 signaling (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P29320};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Most abundant in the heart, brain and lung.
CC -!- INDUCTION: Down-regulated by IL1-beta in neonatal cardiac myocytes.
CC -!- PTM: Autophosphorylates upon activation by EFNA5. Phosphorylation on
CC Tyr-603 mediates interaction with NCK1. Dephosphorylated by PTPN1 (By
CC similarity). {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; U69278; AAC06273.1; -; mRNA.
DR PIR; PT0186; PT0186.
DR RefSeq; NP_113752.1; NM_031564.1.
DR AlphaFoldDB; O08680; -.
DR SMR; O08680; -.
DR STRING; 10116.ENSRNOP00000043263; -.
DR GlyCosmos; O08680; 5 sites, No reported glycans.
DR GlyGen; O08680; 5 sites.
DR iPTMnet; O08680; -.
DR PhosphoSitePlus; O08680; -.
DR SwissPalm; O08680; -.
DR PaxDb; 10116-ENSRNOP00000043263; -.
DR GeneID; 29210; -.
DR KEGG; rno:29210; -.
DR UCSC; RGD:68389; rat.
DR AGR; RGD:68389; -.
DR CTD; 2042; -.
DR RGD; 68389; Epha3.
DR eggNOG; KOG0196; Eukaryota.
DR InParanoid; O08680; -.
DR OrthoDB; 1614410at2759; -.
DR PhylomeDB; O08680; -.
DR BRENDA; 2.7.10.1; 5301.
DR Reactome; R-RNO-2682334; EPH-Ephrin signaling.
DR Reactome; R-RNO-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-RNO-3928665; EPH-ephrin mediated repulsion of cells.
DR PRO; PR:O08680; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0098793; C:presynapse; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005003; F:ephrin receptor activity; ISO:RGD.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
DR GO; GO:0019838; F:growth factor binding; ISO:RGD.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; ISO:RGD.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISO:RGD.
DR GO; GO:0003197; P:endocardial cushion development; ISO:RGD.
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:0001660; P:fever generation; IEP:RGD.
DR GO; GO:0045806; P:negative regulation of endocytosis; ISO:RGD.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISO:RGD.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:RGD.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; ISO:RGD.
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:0034097; P:response to cytokine; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0099560; P:synaptic membrane adhesion; ISO:RGD.
DR CDD; cd10481; EphR_LBD_A3; 1.
DR CDD; cd00063; FN3; 2.
DR CDD; cd05066; PTKc_EphR_A; 1.
DR CDD; cd09544; SAM_EPH-A3; 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; IPR034266; EphA3_rcpt_lig-bd.
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 PANTHER; PTHR46877; EPH RECEPTOR A5; 1.
DR PANTHER; PTHR46877:SF12; EPHRIN TYPE-A RECEPTOR 3; 1.
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; 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 2: Evidence at transcript 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..984
FT /note="Ephrin type-A receptor 3"
FT /id="PRO_0000016804"
FT TOPO_DOM 21..541
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 542..565
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 566..984
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 29..207
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 325..435
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 436..532
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 622..883
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 912..976
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 747
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 629..634
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 654
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 701..707
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 751..752
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 597
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P29320"
FT MOD_RES 603
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P29320"
FT MOD_RES 702
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P29320"
FT MOD_RES 780
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P29320"
FT MOD_RES 938
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29319"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 391
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 404
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 493
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 984 AA; 110228 MW; F170C49312F7A0AB CRC64;
MDCHLSILIL FGCCVLSCSR ELSPQPSNEV NLLDSKTIQG ELGWISYPSH GWEEISGVDE
HYTPIRTYQV CNVMDHSQNN WLRTNWVPRN SAQKIYVELK FTLRDCNSIP LVLGTCKETF
NLYYMESDDD HGVKFLEHQF TKIDTIAADE SFTQMDLGDR ILKLNTEIRE VGPVNKKGFY
LAFQDVGACV ALVSVRVYFK KCPFTVKNLA MFPDTVPMDS QSLVEVRGSC VNNSKEEDPP
RMYCSTEGEW LVPIGKCTCN AGYEERGFIC QACRPGFYKA LDGVAKCTKC PPHSSTQEDG
SMNCRCENNY FRAEKDPPSM ACTRPPSAPR NVISNINETS VILDWSWPLD TGGRKDITFN
IICKKCGWNV RQCEPCSPNV RFLPRQLGLT NTTVTVTDLL AHTNYTFEID AINGVSELSS
PPRQFAAVSI TTNQAAPSPV MTIKKDRTSR NSISLSWQEP EHPNGIILDY EVKYYEKQEQ
ETSYTILRAR GTNVTISSLK PDTTYVFQIR ARTAAGYGTN SRKFEFENSP DSFSISGENS
HVVMIAISAA VAIIVLTVVT YVLVGRFCGY HKSKHSSDEK RLHFGNGHLR LPGLRTYVDP
HTYEDPTQAV HEFAKELDAT NIAIDKVVGA GEFGEVCSGR LKLPSKKEIS VAIKTLKVGY
TEKQRRDFLG EASIMGQFDH PNIIRLEGVV TKSKPVMIVT EYMENGSLDS FLRKHDAQFT
VIQLVGMLRG IASGMKYLSD MGYVHRDLAA RNILINSNLV CKVSDFGLSR VLEDDPEAAY
TTRGGKIPVR WTSPEATAYR KFTSASDVWS YGIVLWEVMS YGERPYWEMS NQDVIKAVDE
GYRLPLPMDC PAALYQLMLD CWQKDRNNRP KFEQIVSILD KLIRNPGSLK IITSAAARPS
NLLLDQSNVD IATFHTTGDW LNGMRTAHCK EIFTGVEYSS CDTIAKISTD DMKKVGVTVV
GPQKKIISSI KALETQSKNG PVPV
//
