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Database: UniProt
Entry: P29319
LinkDB: P29319
Original site: P29319 
ID   EPHA3_MOUSE             Reviewed;         983 AA.
AC   P29319;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-1992, sequence version 1.
DT   19-MAR-2014, entry version 138.
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=mEK4;
DE   AltName: Full=Tyrosine-protein kinase TYRO4;
DE   AltName: Full=Tyrosine-protein kinase receptor ETK1;
DE   Flags: Precursor;
GN   Name=Epha3; Synonyms=Etk1, Mek4, Tyro4;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RC   STRAIN=ICR X Swiss Webster; TISSUE=Embryo;
RX   PubMed=1657122;
RA   Sajjadi F.G., Pasquale E.B., Subramani S.;
RT   "Identification of a new eph-related receptor tyrosine kinase gene
RT   from mouse and chicken that is developmentally regulated and encodes
RT   at least two forms of the receptor.";
RL   New Biol. 3:769-778(1991).
RN   [2]
RP   INTERACTION WITH CRK.
RX   PubMed=11870224;
RA   Lawrenson I.D., Wimmer-Kleikamp S.H., Lock P., Schoenwaelder S.M.,
RA   Down M., Boyd A.W., Alewood P.F., Lackmann M.;
RT   "Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-
RT   expressing 293T and melanoma cells by CrkII and Rho-mediated
RT   signalling.";
RL   J. Cell Sci. 115:1059-1072(2002).
RN   [3]
RP   DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX   PubMed=14585969; DOI=10.1128/MCB.23.22.8092-8098.2003;
RA   Vaidya A., Pniak A., Lemke G., Brown A.;
RT   "EphA3 null mutants do not demonstrate motor axon guidance defects.";
RL   Mol. Cell. Biol. 23:8092-8098(2003).
RN   [4]
RP   DISRUPTION PHENOTYPE, FUNCTION IN HEART DEVELOPMENT, AND DEVELOPMENTAL
RP   STAGE.
RX   PubMed=17046737; DOI=10.1016/j.ydbio.2006.08.058;
RA   Stephen L.J., Fawkes A.L., Verhoeve A., Lemke G., Brown A.;
RT   "A critical role for the EphA3 receptor tyrosine kinase in heart
RT   development.";
RL   Dev. Biol. 302:66-79(2007).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-937, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Mast cell;
RX   PubMed=17947660;
RA   Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA   Kawakami T., Salomon A.R.;
RT   "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT   signaling.";
RL   J. Immunol. 179:5864-5876(2007).
RN   [6]
RP   FUNCTION IN MOTOR AND SENSORY AXONS SEGREGATION.
RX   PubMed=18403711; DOI=10.1126/science.1153758;
RA   Gallarda B.W., Bonanomi D., Mueller D., Brown A., Alaynick W.A.,
RA   Andrews S.E., Lemke G., Pfaff S.L., Marquardt T.;
RT   "Segregation of axial motor and sensory pathways via heterotypic
RT   trans-axonal signaling.";
RL   Science 320:233-236(2008).
RN   [7]
RP   FUNCTION IN CELL MIGRATION, AND INTERACTION WITH NCK1.
RX   PubMed=19505147; DOI=10.1021/bi900831k;
RA   Hu T., Shi G., Larose L., Rivera G.M., Mayer B.J., Zhou R.;
RT   "Regulation of process retraction and cell migration by EphA3 is
RT   mediated by the adaptor protein Nck1.";
RL   Biochemistry 48:6369-6378(2009).
CC   -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously
CC       membrane-bound ephrin family ligands residing on adjacent cells,
CC       leading to contact-dependent bidirectional signaling into
CC       neighboring cells. The signaling pathway downstream of the
CC       receptor is referred to as forward signaling while the signaling
CC       pathway downstream of the ephrin ligand is referred to as reverse
CC       signaling. Highly promiscuous for ephrin-A ligands it binds
CC       preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell
CC       adhesion, cytoskeletal organization and cell migration. Plays a
CC       role in cardiac cells migration and differentiation and regulates
CC       the formation of the atrioventricular canal and septum during
CC       development probably through activation by EFNA1. Involved in the
CC       retinotectal mapping of neurons. May also control the segregation
CC       but not the guidance of motor and sensory axons during
CC       neuromuscular circuit development.
CC   -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
CC       [protein]-L-tyrosine phosphate.
CC   -!- SUBUNIT: Heterotetramer upon binding of the ligand. The
CC       heterotetramer is composed of an ephrin dimer and a receptor
CC       dimer. Oligomerization is probably required to induce biological
CC       responses. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating
CC       EFNA5 extracellular domain shedding by ADAM10 which regulates the
CC       EFNA5-EPHA3 complex internalization and function. Interacts
CC       (phosphorylated) with PTPN1; dephosphorylates EPHA3 and may
CC       regulate its trafficking and function (By similarity). Interacts
CC       (phosphorylated) with CRK; mediates EFNA5-EPHA3 signaling through
CC       RHOA GTPase activation. Interacts with NCK1 (via SH2 domain);
CC       mediates EFNA5-EPHA3 signaling.
CC   -!- SUBCELLULAR LOCATION: Isoform Long: Cell membrane; Single-pass
CC       type I membrane protein.
CC   -!- SUBCELLULAR LOCATION: Isoform Short: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Long;
CC         IsoId=P29319-1; Sequence=Displayed;
CC       Name=Short;
CC         IsoId=P29319-3; Sequence=VSP_041882, VSP_041883;
CC   -!- TISSUE SPECIFICITY: Greatest levels of expression occurring in the
CC       brain, also detected in testis.
CC   -!- DEVELOPMENTAL STAGE: Specifically expressed in heart during its
CC       development by mesenchymal cells of the endocardial cushions.
CC       Expressed in motor neurons at E11.5.
CC   -!- PTM: Autophosphorylates upon activation by EFNA5. Phosphorylation
CC       on Tyr-602 mediates interaction with NCK1. Dephosphorylated by
CC       PTPN1 (By similarity).
CC   -!- DISRUPTION PHENOTYPE: Mice die perinatally due to cardiac failure.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. Ephrin receptor subfamily.
CC   -!- SIMILARITY: Contains 1 Eph LBD (Eph ligand-binding) domain.
CC   -!- SIMILARITY: Contains 2 fibronectin type-III domains.
CC   -!- SIMILARITY: Contains 1 protein kinase domain.
CC   -!- SIMILARITY: Contains 1 SAM (sterile alpha motif) domain.
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DR   EMBL; M68513; AAA39521.1; -; mRNA.
DR   EMBL; M68515; AAA39522.1; -; mRNA.
DR   PIR; A45583; A45583.
DR   UniGene; Mm.1977; -.
DR   ProteinModelPortal; P29319; -.
DR   SMR; P29319; 26-528, 569-906, 909-975.
DR   ChEMBL; CHEMBL2034794; -.
DR   PhosphoSite; P29319; -.
DR   PaxDb; P29319; -.
DR   PRIDE; P29319; -.
DR   MGI; MGI:99612; Epha3.
DR   eggNOG; COG0515; -.
DR   HOVERGEN; HBG062180; -.
DR   InParanoid; P29319; -.
DR   PRO; PR:P29319; -.
DR   CleanEx; MM_EPHA3; -.
DR   Genevestigator; P29319; -.
DR   GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
DR   GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR   GO; GO:0003197; P:endocardial cushion development; IMP:UniProtKB.
DR   GO; GO:0097156; P:fasciculation of motor neuron axon; IMP:UniProtKB.
DR   GO; GO:0097155; P:fasciculation of sensory neuron axon; IMP:UniProtKB.
DR   GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR   GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; IMP:UniProtKB.
DR   GO; GO:0051893; P:regulation of focal adhesion assembly; ISS:UniProtKB.
DR   GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISS:UniProtKB.
DR   GO; GO:0032319; P:regulation of Rho GTPase activity; ISS:UniProtKB.
DR   Gene3D; 1.10.150.50; -; 1.
DR   Gene3D; 2.60.120.260; -; 1.
DR   Gene3D; 2.60.40.10; -; 2.
DR   InterPro; IPR027936; Eph_TM.
DR   InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom.
DR   InterPro; IPR003961; Fibronectin_type3.
DR   InterPro; IPR008979; Galactose-bd-like.
DR   InterPro; IPR009030; Growth_fac_rcpt_N_dom.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR011009; Kinase-like_dom.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR001660; SAM.
DR   InterPro; IPR013761; SAM/pointed.
DR   InterPro; IPR011510; SAM_2.
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; PF00041; fn3; 2.
DR   Pfam; PF07699; GCC2_GCC3; 1.
DR   Pfam; PF07714; Pkinase_Tyr; 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; 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; 2.
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   Alternative splicing; ATP-binding; Cell membrane; Complete proteome;
KW   Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein;
KW   Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase;
KW   Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT   SIGNAL        1     20       By similarity.
FT   CHAIN        21    983       Ephrin type-A receptor 3.
FT                                /FTId=PRO_0000016803.
FT   TOPO_DOM     21    540       Extracellular (Potential).
FT   TRANSMEM    541    564       Helical; (Potential).
FT   TOPO_DOM    565    983       Cytoplasmic (Potential).
FT   DOMAIN       29    206       Eph LBD.
FT   DOMAIN      324    434       Fibronectin type-III 1.
FT   DOMAIN      435    530       Fibronectin type-III 2.
FT   DOMAIN      621    882       Protein kinase.
FT   DOMAIN      911    975       SAM.
FT   NP_BIND     628    633       ATP (By similarity).
FT   NP_BIND     700    706       ATP (By similarity).
FT   NP_BIND     750    751       ATP (By similarity).
FT   MOTIF       981    983       PDZ-binding (Potential).
FT   COMPBIAS    188    321       Cys-rich.
FT   ACT_SITE    746    746       Proton acceptor (By similarity).
FT   BINDING     653    653       ATP (By similarity).
FT   MOD_RES     596    596       Phosphotyrosine; by autocatalysis (By
FT                                similarity).
FT   MOD_RES     602    602       Phosphotyrosine; by autocatalysis (By
FT                                similarity).
FT   MOD_RES     701    701       Phosphotyrosine; by autocatalysis (By
FT                                similarity).
FT   MOD_RES     779    779       Phosphotyrosine; by autocatalysis (By
FT                                similarity).
FT   MOD_RES     937    937       Phosphotyrosine.
FT   CARBOHYD    231    231       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    336    336       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    390    390       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    403    403       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    492    492       N-linked (GlcNAc...) (Potential).
FT   VAR_SEQ     531    537       SFSISGE -> CMYYFSF (in isoform Short).
FT                                /FTId=VSP_041882.
FT   VAR_SEQ     538    983       Missing (in isoform Short).
FT                                /FTId=VSP_041883.
SQ   SEQUENCE   983 AA;  109955 MW;  BE44A6655D8107A2 CRC64;
     MDCHLSILVL LGCCVLSCSG ELSPQPSNEV NLLDSKTIQG ELGWISYPSH GWEEISGVDE
     HYTPIRTYQV CNVMDHSQNN WLRTNWVPRN SAQKIYVELK FTLRDCNSIP LVLGTCKETF
     NLYYMESDDH GVKFREHQFT KIDTIAADES FTQMDLGDRI LKLNTEIREV GPVNKKGFYL
     AFQDVGACVA LVSVRVYFKK CPFTVKNLAM FPDTVPMDSQ SLVEVRGSCV NNSKEEDPPR
     MYCSTEGEWL VPIGKCTCNA GYEERGFICQ ACRPGFYKAS DGAAKCAKCP PHSSTQEDGS
     MNCRCENNYF RAEKDPPSMA CARPPSAPRN VISNINETSV ILDWSWPLDT GGRKDITFNI
     ICKKCGWNVR QCEPCSPNVR FLPRQLGLTN TTVTVTDLLA HTNYTFEIDA VNGVSELSSP
     PRQYAAVSIT TNQAAPSPVM TIKKDRTSRN SISLSWQEPE HPNGIILDYE VKYYQKQEQE
     TSYTILRARG TNVTISSLKP DTTYVFQIRA RTAAGYGTNS RKFEFETSPD SFSISGENSH
     VVMIAISAAV AIIVLTVVTY VLVGRFCGYH KSKHSAEEKR LHFGNGHLKL PGLRTYVDPH
     TYEDPTQAVH EFAKELDATN ISIDKVVGAG EFGEVCSGRL KLPSKKEISV AIKTLKVGYT
     EKQRRDFLGE ASIMGQFDHP NIIRLEGVVT KSKPEMIVTE YMENGSLDSF LRKHDAQFTV
     IQLVGMLRGI ASGMKYLSDM GYVHRDLAAR NILINSNLVC KVSDFGLSRV LEDDPEAAYT
     TRGGKIPIRW TSPEAMSYRK FTSASDVWSY GIVLWEVMSY GERPYSQMSN QDVIKAVDER
     YRLPPPMDCP AALYQLMLDC WQKDRNNRPK FEQIVSILDK LIRNPGSLKI ITSAAARPSN
     LLLDQSNVDI ATFHTTGDWL NGMRTAHCKE IFTGVEYSSC DTIAKISTDD MKKVGVTVVG
     PQKKIISTIK ALETQSKNGP VPV
//
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