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P29319 (EPHA3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Epha3
Synonyms:Etk1, Mek4, Tyro4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length983 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.6 Ref.7

Catalytic activity

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

Subunit structure

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. Ref.2 Ref.7

Subcellular location

Isoform Long: Cell membrane; Single-pass type I membrane protein.

Isoform Short: Secreted.

Tissue specificity

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

Developmental stage

Specifically expressed in heart during its development by mesenchymal cells of the endocardial cushions. Expressed in motor neurons at E11.5. Ref.3 Ref.4

Post-translational modification

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

Disruption phenotype

Mice die perinatally due to cardiac failure. Ref.3 Ref.4

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.

Contains 1 Eph LBD (Eph ligand-binding) domain.

Contains 2 fibronectin type-III domains.

Contains 1 protein kinase domain.

Contains 1 SAM (sterile alpha motif) domain.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell migration

Inferred from mutant phenotype Ref.4. Source: UniProtKB

endocardial cushion development

Inferred from mutant phenotype Ref.4. Source: UniProtKB

ephrin receptor signaling pathway

Inferred from direct assay PubMed 21135139. Source: UniProtKB

fasciculation of motor neuron axon

Inferred from mutant phenotype Ref.6. Source: UniProtKB

fasciculation of sensory neuron axon

Inferred from mutant phenotype PubMed 21791286. Source: UniProtKB

regulation of Rho GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of actin cytoskeleton organization

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of epithelial to mesenchymal transition

Inferred from mutant phenotype Ref.4. Source: UniProtKB

regulation of focal adhesion assembly

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of microtubule cytoskeleton organization

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentearly endosome

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

GPI-linked ephrin receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

ephrin receptor activity

Inferred from direct assay PubMed 15145949. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P29319-1)

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.
Isoform Short (identifier: P29319-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 By similarity
Chain21 – 983963Ephrin type-A receptor 3
PRO_0000016803

Regions

Topological domain21 – 540520Extracellular Potential
Transmembrane541 – 56424Helical; Potential
Topological domain565 – 983419Cytoplasmic Potential
Domain29 – 206178Eph LBD
Domain324 – 434111Fibronectin type-III 1
Domain435 – 53096Fibronectin type-III 2
Domain621 – 882262Protein kinase
Domain911 – 97565SAM
Nucleotide binding628 – 6336ATP By similarity
Nucleotide binding700 – 7067ATP By similarity
Nucleotide binding750 – 7512ATP By similarity
Motif981 – 9833PDZ-binding Potential
Compositional bias188 – 321134Cys-rich

Sites

Active site7461Proton acceptor By similarity
Binding site6531ATP By similarity

Amino acid modifications

Modified residue5961Phosphotyrosine; by autocatalysis By similarity
Modified residue6021Phosphotyrosine; by autocatalysis By similarity
Modified residue7011Phosphotyrosine; by autocatalysis By similarity
Modified residue7791Phosphotyrosine; by autocatalysis By similarity
Modified residue9371Phosphotyrosine Ref.5
Glycosylation2311N-linked (GlcNAc...) Potential
Glycosylation3361N-linked (GlcNAc...) Potential
Glycosylation3901N-linked (GlcNAc...) Potential
Glycosylation4031N-linked (GlcNAc...) Potential
Glycosylation4921N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence531 – 5377SFSISGE → CMYYFSF in isoform Short.
VSP_041882
Alternative sequence538 – 983446Missing in isoform Short.
VSP_041883

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified December 1, 1992. Version 1.
Checksum: BE44A6655D8107A2

FASTA983109,955
        10         20         30         40         50         60 
MDCHLSILVL LGCCVLSCSG ELSPQPSNEV NLLDSKTIQG ELGWISYPSH GWEEISGVDE 

        70         80         90        100        110        120 
HYTPIRTYQV CNVMDHSQNN WLRTNWVPRN SAQKIYVELK FTLRDCNSIP LVLGTCKETF 

       130        140        150        160        170        180 
NLYYMESDDH GVKFREHQFT KIDTIAADES FTQMDLGDRI LKLNTEIREV GPVNKKGFYL 

       190        200        210        220        230        240 
AFQDVGACVA LVSVRVYFKK CPFTVKNLAM FPDTVPMDSQ SLVEVRGSCV NNSKEEDPPR 

       250        260        270        280        290        300 
MYCSTEGEWL VPIGKCTCNA GYEERGFICQ ACRPGFYKAS DGAAKCAKCP PHSSTQEDGS 

       310        320        330        340        350        360 
MNCRCENNYF RAEKDPPSMA CARPPSAPRN VISNINETSV ILDWSWPLDT GGRKDITFNI 

       370        380        390        400        410        420 
ICKKCGWNVR QCEPCSPNVR FLPRQLGLTN TTVTVTDLLA HTNYTFEIDA VNGVSELSSP 

       430        440        450        460        470        480 
PRQYAAVSIT TNQAAPSPVM TIKKDRTSRN SISLSWQEPE HPNGIILDYE VKYYQKQEQE 

       490        500        510        520        530        540 
TSYTILRARG TNVTISSLKP DTTYVFQIRA RTAAGYGTNS RKFEFETSPD SFSISGENSH 

       550        560        570        580        590        600 
VVMIAISAAV AIIVLTVVTY VLVGRFCGYH KSKHSAEEKR LHFGNGHLKL PGLRTYVDPH 

       610        620        630        640        650        660 
TYEDPTQAVH EFAKELDATN ISIDKVVGAG EFGEVCSGRL KLPSKKEISV AIKTLKVGYT 

       670        680        690        700        710        720 
EKQRRDFLGE ASIMGQFDHP NIIRLEGVVT KSKPEMIVTE YMENGSLDSF LRKHDAQFTV 

       730        740        750        760        770        780 
IQLVGMLRGI ASGMKYLSDM GYVHRDLAAR NILINSNLVC KVSDFGLSRV LEDDPEAAYT 

       790        800        810        820        830        840 
TRGGKIPIRW TSPEAMSYRK FTSASDVWSY GIVLWEVMSY GERPYSQMSN QDVIKAVDER 

       850        860        870        880        890        900 
YRLPPPMDCP AALYQLMLDC WQKDRNNRPK FEQIVSILDK LIRNPGSLKI ITSAAARPSN 

       910        920        930        940        950        960 
LLLDQSNVDI ATFHTTGDWL NGMRTAHCKE IFTGVEYSSC DTIAKISTDD MKKVGVTVVG 

       970        980 
PQKKIISTIK ALETQSKNGP VPV 

« Hide

Isoform Short [UniParc].

Checksum: D698CD2FF29426A5
Show »

FASTA53760,513

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M68513 mRNA. Translation: AAA39521.1.
M68515 mRNA. Translation: AAA39522.1.
PIRA45583.
UniGeneMm.1977.

3D structure databases

ProteinModelPortalP29319.
SMRP29319. Positions 26-528, 569-906, 909-975.
ModBaseSearch...
MobiDBSearch...

Chemistry

ChEMBLCHEMBL2034794.

PTM databases

PhosphoSiteP29319.

Proteomic databases

PaxDbP29319.
PRIDEP29319.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:99612. Epha3.

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG062180.
InParanoidP29319.
PhylomeDBP29319.

Gene expression databases

CleanExMM_EPHA3.
GenevestigatorP29319.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProIPR027936. 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]
PfamPF14575. 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]
PIRSFPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEPS01186. 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]
ProtoNetSearch...

Other

PROP29319.
SOURCESearch...

Entry information

Entry nameEPHA3_MOUSE
AccessionPrimary (citable) accession number: P29319
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: April 16, 2014
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot