Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ephrin type-A receptor 3

Gene

Epha3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

  • ATP binding Source: UniProtKB-KW
  • ephrin receptor activity Source: MGI
  • GPI-linked ephrin receptor activity Source: UniProtKB

GO - Biological processi

  • cell migration Source: UniProtKB
  • cellular response to retinoic acid Source: MGI
  • endocardial cushion development Source: UniProtKB
  • ephrin receptor signaling pathway Source: UniProtKB
  • fasciculation of motor neuron axon Source: UniProtKB
  • fasciculation of sensory neuron axon Source: UniProtKB
  • positive regulation of neuron projection development Source: MGI
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • regulation of epithelial to mesenchymal transition Source: UniProtKB
  • regulation of focal adhesion assembly Source: UniProtKB
  • regulation of GTPase activity Source: UniProtKB
  • regulation of microtubule cytoskeleton organization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.

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 Componenti: Unplaced

Organism-specific databases

MGIiMGI:99612. Epha3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 540520ExtracellularSequence AnalysisAdd
BLAST
Transmembranei541 – 56424HelicalSequence AnalysisAdd
BLAST
Topological domaini565 – 983419CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

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

MaxQBiP29319.
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.

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

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000066554.

Structurei

3D structure databases

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

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. FN3_dom.
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. AlignAdd to basket

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

        10         20         30         40         50
MDCHLSILVL LGCCVLSCSG ELSPQPSNEV NLLDSKTIQG ELGWISYPSH
60 70 80 90 100
GWEEISGVDE HYTPIRTYQV CNVMDHSQNN WLRTNWVPRN SAQKIYVELK
110 120 130 140 150
FTLRDCNSIP LVLGTCKETF NLYYMESDDH GVKFREHQFT KIDTIAADES
160 170 180 190 200
FTQMDLGDRI LKLNTEIREV GPVNKKGFYL AFQDVGACVA LVSVRVYFKK
210 220 230 240 250
CPFTVKNLAM FPDTVPMDSQ SLVEVRGSCV NNSKEEDPPR MYCSTEGEWL
260 270 280 290 300
VPIGKCTCNA GYEERGFICQ ACRPGFYKAS DGAAKCAKCP PHSSTQEDGS
310 320 330 340 350
MNCRCENNYF RAEKDPPSMA CARPPSAPRN VISNINETSV ILDWSWPLDT
360 370 380 390 400
GGRKDITFNI ICKKCGWNVR QCEPCSPNVR FLPRQLGLTN TTVTVTDLLA
410 420 430 440 450
HTNYTFEIDA VNGVSELSSP PRQYAAVSIT TNQAAPSPVM TIKKDRTSRN
460 470 480 490 500
SISLSWQEPE HPNGIILDYE VKYYQKQEQE TSYTILRARG TNVTISSLKP
510 520 530 540 550
DTTYVFQIRA RTAAGYGTNS RKFEFETSPD SFSISGENSH VVMIAISAAV
560 570 580 590 600
AIIVLTVVTY VLVGRFCGYH KSKHSAEEKR LHFGNGHLKL PGLRTYVDPH
610 620 630 640 650
TYEDPTQAVH EFAKELDATN ISIDKVVGAG EFGEVCSGRL KLPSKKEISV
660 670 680 690 700
AIKTLKVGYT EKQRRDFLGE ASIMGQFDHP NIIRLEGVVT KSKPEMIVTE
710 720 730 740 750
YMENGSLDSF LRKHDAQFTV IQLVGMLRGI ASGMKYLSDM GYVHRDLAAR
760 770 780 790 800
NILINSNLVC KVSDFGLSRV LEDDPEAAYT TRGGKIPIRW TSPEAMSYRK
810 820 830 840 850
FTSASDVWSY GIVLWEVMSY GERPYSQMSN QDVIKAVDER YRLPPPMDCP
860 870 880 890 900
AALYQLMLDC WQKDRNNRPK FEQIVSILDK LIRNPGSLKI ITSAAARPSN
910 920 930 940 950
LLLDQSNVDI ATFHTTGDWL NGMRTAHCKE IFTGVEYSSC DTIAKISTDD
960 970 980
MKKVGVTVVG PQKKIISTIK ALETQSKNGP VPV
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
M68513 mRNA. Translation: AAA39521.1.
M68515 mRNA. Translation: AAA39522.1.
PIRiA45583.
UniGeneiMm.1977.

3D structure databases

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

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000066554.

Chemistry

BindingDBiP29319.
ChEMBLiCHEMBL2034794.
GuidetoPHARMACOLOGYi1823.

PTM databases

PhosphoSiteiP29319.

Proteomic databases

MaxQBiP29319.
PaxDbiP29319.
PRIDEiP29319.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:99612. Epha3.

Phylogenomic databases

eggNOGiCOG0515.
HOVERGENiHBG062180.
InParanoidiP29319.
PhylomeDBiP29319.

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.

Miscellaneous databases

PROiP29319.
SOURCEiSearch...

Gene expression databases

CleanExiMM_EPHA3.

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. FN3_dom.
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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: June 24, 2015
This is version 148 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.