EPHA3_CHICK
ID EPHA3_CHICK Reviewed; 983 AA.
AC P29318;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 167.
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=cEK4;
DE AltName: Full=Tyrosine-protein kinase receptor ETK1;
DE Flags: Precursor;
GN Name=EPHA3; Synonyms=CEK4, ETK1;
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].
RX PubMed=1657122;
RA Sajjadi F.G., Pasquale E.B., Subramani S.;
RT "Identification of a new eph-related receptor tyrosine kinase gene from
RT mouse and chicken that is developmentally regulated and encodes at least
RT two forms of the receptor.";
RL New Biol. 3:769-778(1991).
RN [2]
RP FUNCTION IN RETINOTECTAL MAPPING.
RX PubMed=15014130; DOI=10.1523/jneurosci.0239-03.2004;
RA Feldheim D.A., Nakamoto M., Osterfield M., Gale N.W., DeChiara T.M.,
RA Rohatgi R., Yancopoulos G.D., Flanagan J.G.;
RT "Loss-of-function analysis of EphA receptors in retinotectal mapping.";
RL J. Neurosci. 24:2542-2550(2004).
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. {ECO:0000269|PubMed:15014130}.
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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P29320};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the developing brain and
CC embryonic tissues. In adult, the greatest levels of expression occur in
CC the brain. It is expressed in a graded manner across the retina with
CC the highest expression at its temporal pole. Detectable in all other
CC adult tissues examined, except the liver.
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; M68514; AAA48666.1; -; mRNA.
DR PIR; B45583; B45583.
DR RefSeq; NP_990761.1; NM_205430.2.
DR AlphaFoldDB; P29318; -.
DR SMR; P29318; -.
DR IntAct; P29318; 1.
DR STRING; 9031.ENSGALP00000024798; -.
DR PaxDb; P29318; -.
DR GeneID; 396402; -.
DR KEGG; gga:396402; -.
DR CTD; 2042; -.
DR VEuPathDB; HostDB:geneid_396402; -.
DR eggNOG; KOG0196; Eukaryota.
DR InParanoid; P29318; -.
DR OrthoDB; 933071at2759; -.
DR PhylomeDB; P29318; -.
DR BRENDA; 2.7.10.1; 1306.
DR PRO; PR:P29318; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005003; F:ephrin receptor activity; ISS:AgBase.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
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: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 CDD; cd10481; EphR_LBD_A3; 1.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
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; 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; 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 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..19
FT /evidence="ECO:0000250"
FT CHAIN 20..983
FT /note="Ephrin type-A receptor 3"
FT /id="PRO_0000016805"
FT TOPO_DOM 20..540
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 541..564
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 565..983
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..206
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 324..434
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 435..530
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 981..983
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 628..633
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 BINDING 700..706
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 750..751
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 701
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 779
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT CARBOHYD 231
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 336
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 390
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 403
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 492
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 983 AA; 109910 MW; E8895F0BDF77651E CRC64;
MDRRRLPLLL LCAALGSAGR LSARPGNEVN LLDSKTIQGE LGWISYPSHG WEEISGVDEH
YTPIRTYQES NVMDHSQNNW LRTNWIPRNS AQKIYVELKF TLRDCNSIPL VLGTCKETFN
LYYMESDDDH LAKFREHQFT KIDTIAADES FTQMDLGDRI LKLNTEVREV GPVSKKGFYL
AFQDVGACVA LVSVRVYFKK CPFTVKNLAM FPDTVPMDSQ SLVEVRGSCV NHSKEEEPPK
MYCSTEGEWL VPIGKCLCNA GYEERGFACQ ACRPGFYKAS AGNVKCAKCP PHSSTYEDAS
LNCRCEKNYF RSEKDPPSMA CTRPPSAPRN VISNINETSV ILDWSWPLDT GGRKDVTFNI
ICKKCGGSSK ICEPCSDNVR FLPRQTGLTN TTVTVVDLLA HTNYTFEIDA VNGVSDLSTL
SRQFAAVSIT TNQAAPSPIT VIRKDRTSRN SVSLSWQEPE HPNGIILDYE VKYYEKQEQE
TSYTILRAKS TNVTISGLKP DTTYVFQIRA RTAARYGTSS RKFEFETSPD SFSISSENSQ
VVMIAISAAV AIILLTVVVY VLIGRFCGYK KSKHGTDEKR LHFGNGHLKL PGLRTYVDPH
TYEDPNQAVH EFAKELDASN ISIDKVVGAG EFGEVCSGRL KLPSKKEISV AIKTLKAGYT
EKQRRDFLGE ASIMGQFDHP NIIRLEGVVT KSKPVMIVTE YMENGSLDSF LRKHDAQFTV
IQLVGMLRGI ASGMKYLSDM GYVHRDLAAR NILINSNLVC KVSDFGLSRV LEDDPEAAYT
TRGGKIPIRW TSPEAIAYRK FTSASDAWSY GIVLWEVMSY GERPYWEMSF QDVIKAVDEG
YRLPPPMDCP AALYQLMLDC WQKDRNNRPK FEQIVSILDK LIRNPSSLKI ITNAAARPSN
LLLDQSNIDI SAFRTAGDWL NGFRTGQCKG IFTGVEYSSC DTIAKISTDD MKKVGVTVVG
PQKKIVSSIK TLETHTKNSP VPV
