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P29319

- EPHA3_MOUSE

UniProt

P29319 - EPHA3_MOUSE

Protein

Ephrin type-A receptor 3

Gene

Epha3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 1 (01 Dec 1992)
      Previous versions | rss
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    Functioni

    Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development.3 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei653 – 6531ATPPROSITE-ProRule annotation
    Active sitei746 – 7461Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi628 – 6336ATPPROSITE-ProRule annotation
    Nucleotide bindingi700 – 7067ATPPROSITE-ProRule annotation
    Nucleotide bindingi750 – 7512ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. ephrin receptor activity Source: MGI
    3. GPI-linked ephrin receptor activity Source: UniProtKB

    GO - Biological processi

    1. cell migration Source: UniProtKB
    2. endocardial cushion development Source: UniProtKB
    3. ephrin receptor signaling pathway Source: UniProtKB
    4. fasciculation of motor neuron axon Source: UniProtKB
    5. fasciculation of sensory neuron axon Source: UniProtKB
    6. regulation of actin cytoskeleton organization Source: UniProtKB
    7. regulation of epithelial to mesenchymal transition Source: UniProtKB
    8. regulation of focal adhesion assembly Source: UniProtKB
    9. regulation of microtubule cytoskeleton organization Source: UniProtKB
    10. regulation of Rho GTPase activity Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ephrin type-A receptor 3 (EC:2.7.10.1)
    Alternative name(s):
    EPH-like kinase 4
    Short name:
    EK4
    Short name:
    mEK4
    Tyrosine-protein kinase TYRO4
    Tyrosine-protein kinase receptor ETK1
    Gene namesi
    Name:Epha3
    Synonyms:Etk1, Mek4, Tyro4
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:99612. Epha3.

    Subcellular locationi

    GO - Cellular componenti

    1. early endosome Source: UniProtKB
    2. extracellular region Source: UniProtKB-SubCell
    3. integral component of plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    Pathology & Biotechi

    Disruption phenotypei

    Mice die perinatally due to cardiac failure.2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2020By similarityAdd
    BLAST
    Chaini21 – 983963Ephrin type-A receptor 3PRO_0000016803Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi231 – 2311N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi336 – 3361N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi390 – 3901N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi403 – 4031N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi492 – 4921N-linked (GlcNAc...)Sequence Analysis
    Modified residuei596 – 5961Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei602 – 6021Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei701 – 7011Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei779 – 7791Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei937 – 9371Phosphotyrosine1 Publication

    Post-translational modificationi

    Autophosphorylates upon activation by EFNA5. Phosphorylation on Tyr-602 mediates interaction with NCK1. Dephosphorylated by PTPN1 By similarity.By similarity

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiP29319.
    PRIDEiP29319.

    PTM databases

    PhosphoSiteiP29319.

    Expressioni

    Tissue specificityi

    Greatest levels of expression occurring in the brain, also detected in testis.

    Developmental stagei

    Specifically expressed in heart during its development by mesenchymal cells of the endocardial cushions. Expressed in motor neurons at E11.5.2 Publications

    Gene expression databases

    CleanExiMM_EPHA3.
    GenevestigatoriP29319.

    Interactioni

    Subunit structurei

    Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function. Interacts (phosphorylated) with PTPN1; dephosphorylates EPHA3 and may regulate its trafficking and function By similarity. Interacts (phosphorylated) with CRK; mediates EFNA5-EPHA3 signaling through RHOA GTPase activation. Interacts with NCK1 (via SH2 domain); mediates EFNA5-EPHA3 signaling.By similarity2 Publications

    Structurei

    3D structure databases

    ProteinModelPortaliP29319.
    SMRiP29319. Positions 26-528, 569-906, 909-975.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini21 – 540520ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini565 – 983419CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei541 – 56424HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini29 – 206178Eph LBDPROSITE-ProRule annotationAdd
    BLAST
    Domaini324 – 434111Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini435 – 53096Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini621 – 882262Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini911 – 97565SAMPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi981 – 9833PDZ-bindingSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi188 – 321134Cys-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation
    Contains 1 Eph LBD (Eph ligand-binding) domain.PROSITE-ProRule annotation
    Contains 2 fibronectin type-III domains.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    HOVERGENiHBG062180.
    InParanoidiP29319.
    PhylomeDBiP29319.

    Family and domain databases

    Gene3Di1.10.150.50. 1 hit.
    2.60.120.260. 1 hit.
    2.60.40.10. 2 hits.
    InterProiIPR027936. Eph_TM.
    IPR001090. Ephrin_rcpt_lig-bd_dom.
    IPR003961. Fibronectin_type3.
    IPR008979. Galactose-bd-like.
    IPR009030. Growth_fac_rcpt_N_dom.
    IPR013783. Ig-like_fold.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001660. SAM.
    IPR013761. SAM/pointed.
    IPR011510. SAM_2.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR016257. Tyr_kinase_ephrin_rcpt.
    IPR001426. Tyr_kinase_rcpt_V_CS.
    [Graphical view]
    PfamiPF14575. EphA2_TM. 1 hit.
    PF01404. Ephrin_lbd. 1 hit.
    PF00041. fn3. 2 hits.
    PF07699. GCC2_GCC3. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF07647. SAM_2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00615. EPH_lbd. 1 hit.
    SM00060. FN3. 2 hits.
    SM00454. SAM. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF47769. SSF47769. 1 hit.
    SSF49265. SSF49265. 1 hit.
    SSF49785. SSF49785. 1 hit.
    SSF56112. SSF56112. 1 hit.
    SSF57184. SSF57184. 2 hits.
    PROSITEiPS01186. EGF_2. 1 hit.
    PS51550. EPH_LBD. 1 hit.
    PS50853. FN3. 2 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS00790. RECEPTOR_TYR_KIN_V_1. 1 hit.
    PS00791. RECEPTOR_TYR_KIN_V_2. 1 hit.
    PS50105. SAM_DOMAIN. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform Long (identifier: P29319-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MDCHLSILVL LGCCVLSCSG ELSPQPSNEV NLLDSKTIQG ELGWISYPSH    50
    GWEEISGVDE HYTPIRTYQV CNVMDHSQNN WLRTNWVPRN SAQKIYVELK 100
    FTLRDCNSIP LVLGTCKETF NLYYMESDDH GVKFREHQFT KIDTIAADES 150
    FTQMDLGDRI LKLNTEIREV GPVNKKGFYL AFQDVGACVA LVSVRVYFKK 200
    CPFTVKNLAM FPDTVPMDSQ SLVEVRGSCV NNSKEEDPPR MYCSTEGEWL 250
    VPIGKCTCNA GYEERGFICQ ACRPGFYKAS DGAAKCAKCP PHSSTQEDGS 300
    MNCRCENNYF RAEKDPPSMA CARPPSAPRN VISNINETSV ILDWSWPLDT 350
    GGRKDITFNI ICKKCGWNVR QCEPCSPNVR FLPRQLGLTN TTVTVTDLLA 400
    HTNYTFEIDA VNGVSELSSP PRQYAAVSIT TNQAAPSPVM TIKKDRTSRN 450
    SISLSWQEPE HPNGIILDYE VKYYQKQEQE TSYTILRARG TNVTISSLKP 500
    DTTYVFQIRA RTAAGYGTNS RKFEFETSPD SFSISGENSH VVMIAISAAV 550
    AIIVLTVVTY VLVGRFCGYH KSKHSAEEKR LHFGNGHLKL PGLRTYVDPH 600
    TYEDPTQAVH EFAKELDATN ISIDKVVGAG EFGEVCSGRL KLPSKKEISV 650
    AIKTLKVGYT EKQRRDFLGE ASIMGQFDHP NIIRLEGVVT KSKPEMIVTE 700
    YMENGSLDSF LRKHDAQFTV IQLVGMLRGI ASGMKYLSDM GYVHRDLAAR 750
    NILINSNLVC KVSDFGLSRV LEDDPEAAYT TRGGKIPIRW TSPEAMSYRK 800
    FTSASDVWSY GIVLWEVMSY GERPYSQMSN QDVIKAVDER YRLPPPMDCP 850
    AALYQLMLDC WQKDRNNRPK FEQIVSILDK LIRNPGSLKI ITSAAARPSN 900
    LLLDQSNVDI ATFHTTGDWL NGMRTAHCKE IFTGVEYSSC DTIAKISTDD 950
    MKKVGVTVVG PQKKIISTIK ALETQSKNGP VPV 983
    Length:983
    Mass (Da):109,955
    Last modified:December 1, 1992 - v1
    Checksum:iBE44A6655D8107A2
    GO
    Isoform Short (identifier: P29319-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         531-537: SFSISGE → CMYYFSF
         538-983: Missing.

    Show »
    Length:537
    Mass (Da):60,513
    Checksum:iD698CD2FF29426A5
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei531 – 5377SFSISGE → CMYYFSF in isoform Short. 1 PublicationVSP_041882
    Alternative sequencei538 – 983446Missing in isoform Short. 1 PublicationVSP_041883Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M68513 mRNA. Translation: AAA39521.1.
    M68515 mRNA. Translation: AAA39522.1.
    PIRiA45583.
    UniGeneiMm.1977.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M68513 mRNA. Translation: AAA39521.1 .
    M68515 mRNA. Translation: AAA39522.1 .
    PIRi A45583.
    UniGenei Mm.1977.

    3D structure databases

    ProteinModelPortali P29319.
    SMRi P29319. Positions 26-528, 569-906, 909-975.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    ChEMBLi CHEMBL2034794.

    PTM databases

    PhosphoSitei P29319.

    Proteomic databases

    PaxDbi P29319.
    PRIDEi P29319.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    MGIi MGI:99612. Epha3.

    Phylogenomic databases

    eggNOGi COG0515.
    HOVERGENi HBG062180.
    InParanoidi P29319.
    PhylomeDBi P29319.

    Miscellaneous databases

    PROi P29319.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_EPHA3.
    Genevestigatori P29319.

    Family and domain databases

    Gene3Di 1.10.150.50. 1 hit.
    2.60.120.260. 1 hit.
    2.60.40.10. 2 hits.
    InterProi IPR027936. Eph_TM.
    IPR001090. Ephrin_rcpt_lig-bd_dom.
    IPR003961. Fibronectin_type3.
    IPR008979. Galactose-bd-like.
    IPR009030. Growth_fac_rcpt_N_dom.
    IPR013783. Ig-like_fold.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001660. SAM.
    IPR013761. SAM/pointed.
    IPR011510. SAM_2.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR016257. Tyr_kinase_ephrin_rcpt.
    IPR001426. Tyr_kinase_rcpt_V_CS.
    [Graphical view ]
    Pfami PF14575. EphA2_TM. 1 hit.
    PF01404. Ephrin_lbd. 1 hit.
    PF00041. fn3. 2 hits.
    PF07699. GCC2_GCC3. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF07647. SAM_2. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000666. TyrPK_ephrin_receptor. 1 hit.
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00615. EPH_lbd. 1 hit.
    SM00060. FN3. 2 hits.
    SM00454. SAM. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47769. SSF47769. 1 hit.
    SSF49265. SSF49265. 1 hit.
    SSF49785. SSF49785. 1 hit.
    SSF56112. SSF56112. 1 hit.
    SSF57184. SSF57184. 2 hits.
    PROSITEi PS01186. EGF_2. 1 hit.
    PS51550. EPH_LBD. 1 hit.
    PS50853. FN3. 2 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS00790. RECEPTOR_TYR_KIN_V_1. 1 hit.
    PS00791. RECEPTOR_TYR_KIN_V_2. 1 hit.
    PS50105. SAM_DOMAIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Identification of a new eph-related receptor tyrosine kinase gene from mouse and chicken that is developmentally regulated and encodes at least two forms of the receptor."
      Sajjadi F.G., Pasquale E.B., Subramani S.
      New Biol. 3:769-778(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
      Strain: ICR X Swiss Webster.
      Tissue: Embryo.
    2. "Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling."
      Lawrenson I.D., Wimmer-Kleikamp S.H., Lock P., Schoenwaelder S.M., Down M., Boyd A.W., Alewood P.F., Lackmann M.
      J. Cell Sci. 115:1059-1072(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CRK.
    3. "EphA3 null mutants do not demonstrate motor axon guidance defects."
      Vaidya A., Pniak A., Lemke G., Brown A.
      Mol. Cell. Biol. 23:8092-8098(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
    4. "A critical role for the EphA3 receptor tyrosine kinase in heart development."
      Stephen L.J., Fawkes A.L., Verhoeve A., Lemke G., Brown A.
      Dev. Biol. 302:66-79(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION IN HEART DEVELOPMENT, DEVELOPMENTAL STAGE.
    5. "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
      Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
      J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-937, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Mast cell.
    6. "Segregation of axial motor and sensory pathways via heterotypic trans-axonal signaling."
      Gallarda B.W., Bonanomi D., Mueller D., Brown A., Alaynick W.A., Andrews S.E., Lemke G., Pfaff S.L., Marquardt T.
      Science 320:233-236(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN MOTOR AND SENSORY AXONS SEGREGATION.
    7. "Regulation of process retraction and cell migration by EphA3 is mediated by the adaptor protein Nck1."
      Hu T., Shi G., Larose L., Rivera G.M., Mayer B.J., Zhou R.
      Biochemistry 48:6369-6378(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CELL MIGRATION, INTERACTION WITH NCK1.

    Entry informationi

    Entry nameiEPHA3_MOUSE
    AccessioniPrimary (citable) accession number: P29319
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 1992
    Last sequence update: December 1, 1992
    Last modified: October 1, 2014
    This is version 141 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3