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O08680 (EPHA3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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=rEK4
Tyrosine-protein kinase TYRO4
Gene names
Name:Epha3
Synonyms:Rek4, Tyro4
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length984 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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 By similarity.

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. Interacts (phosphorylated) with CRK; mediates EFNA5-EPHA3 signaling through RHOA GTPase activation. Interacts with NCK1 (via SH2 domain); mediates EFNA5-EPHA3 signaling By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity.

Tissue specificity

Most abundant in the heart, brain and lung.

Induction

Down-regulated by IL1-beta in neonatal cardiac myocytes.

Post-translational modification

Autophosphorylates upon activation by EFNA5. Phosphorylation on Tyr-603 mediates interaction with NCK1. Dephosphorylated by PTPN1 By similarity.

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
   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 sequence or structural similarity. Source: UniProtKB

ephrin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

fasciculation of motor neuron axon

Inferred from sequence or structural similarity. Source: UniProtKB

fasciculation of sensory neuron axon

Inferred from sequence or structural similarity. Source: UniProtKB

fever generation

Inferred from expression pattern PubMed 15671251. Source: RGD

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 sequence or structural similarity. 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

response to cytokine

Inferred from expression pattern Ref.1. Source: RGD

response to lipopolysaccharide

Inferred from expression pattern PubMed 15671251. Source: RGD

   Cellular_componentearly endosome

Inferred from sequence or structural similarity. Source: UniProtKB

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

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 By similarity
Chain21 – 984964Ephrin type-A receptor 3
PRO_0000016804

Regions

Topological domain21 – 541521Extracellular Potential
Transmembrane542 – 56524Helical; Potential
Topological domain566 – 984419Cytoplasmic Potential
Domain29 – 207179Eph LBD
Domain325 – 435111Fibronectin type-III 1
Domain436 – 53297Fibronectin type-III 2
Domain622 – 883262Protein kinase
Domain912 – 97665SAM
Nucleotide binding629 – 6346ATP By similarity
Nucleotide binding701 – 7077ATP By similarity
Nucleotide binding751 – 7522ATP By similarity
Motif982 – 9843PDZ-binding Potential
Compositional bias189 – 322134Cys-rich

Sites

Active site7471Proton acceptor By similarity
Binding site6541ATP By similarity

Amino acid modifications

Modified residue5971Phosphotyrosine; by autocatalysis By similarity
Modified residue6031Phosphotyrosine; by autocatalysis By similarity
Modified residue7021Phosphotyrosine; by autocatalysis By similarity
Modified residue7801Phosphotyrosine; by autocatalysis By similarity
Modified residue9381Phosphotyrosine By similarity
Glycosylation2321N-linked (GlcNAc...) Potential
Glycosylation3371N-linked (GlcNAc...) Potential
Glycosylation3911N-linked (GlcNAc...) Potential
Glycosylation4041N-linked (GlcNAc...) Potential
Glycosylation4931N-linked (GlcNAc...) Potential

Sequences

Sequence LengthMass (Da)Tools
O08680 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: F170C49312F7A0AB

FASTA984110,228
        10         20         30         40         50         60 
MDCHLSILIL FGCCVLSCSR ELSPQPSNEV NLLDSKTIQG ELGWISYPSH GWEEISGVDE 

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

       130        140        150        160        170        180 
NLYYMESDDD HGVKFLEHQF TKIDTIAADE SFTQMDLGDR ILKLNTEIRE VGPVNKKGFY 

       190        200        210        220        230        240 
LAFQDVGACV ALVSVRVYFK KCPFTVKNLA MFPDTVPMDS QSLVEVRGSC VNNSKEEDPP 

       250        260        270        280        290        300 
RMYCSTEGEW LVPIGKCTCN AGYEERGFIC QACRPGFYKA LDGVAKCTKC PPHSSTQEDG 

       310        320        330        340        350        360 
SMNCRCENNY FRAEKDPPSM ACTRPPSAPR NVISNINETS VILDWSWPLD TGGRKDITFN 

       370        380        390        400        410        420 
IICKKCGWNV RQCEPCSPNV RFLPRQLGLT NTTVTVTDLL AHTNYTFEID AINGVSELSS 

       430        440        450        460        470        480 
PPRQFAAVSI TTNQAAPSPV MTIKKDRTSR NSISLSWQEP EHPNGIILDY EVKYYEKQEQ 

       490        500        510        520        530        540 
ETSYTILRAR GTNVTISSLK PDTTYVFQIR ARTAAGYGTN SRKFEFENSP DSFSISGENS 

       550        560        570        580        590        600 
HVVMIAISAA VAIIVLTVVT YVLVGRFCGY HKSKHSSDEK RLHFGNGHLR LPGLRTYVDP 

       610        620        630        640        650        660 
HTYEDPTQAV HEFAKELDAT NIAIDKVVGA GEFGEVCSGR LKLPSKKEIS VAIKTLKVGY 

       670        680        690        700        710        720 
TEKQRRDFLG EASIMGQFDH PNIIRLEGVV TKSKPVMIVT EYMENGSLDS FLRKHDAQFT 

       730        740        750        760        770        780 
VIQLVGMLRG IASGMKYLSD MGYVHRDLAA RNILINSNLV CKVSDFGLSR VLEDDPEAAY 

       790        800        810        820        830        840 
TTRGGKIPVR WTSPEATAYR KFTSASDVWS YGIVLWEVMS YGERPYWEMS NQDVIKAVDE 

       850        860        870        880        890        900 
GYRLPLPMDC PAALYQLMLD CWQKDRNNRP KFEQIVSILD KLIRNPGSLK IITSAAARPS 

       910        920        930        940        950        960 
NLLLDQSNVD IATFHTTGDW LNGMRTAHCK EIFTGVEYSS CDTIAKISTD DMKKVGVTVV 

       970        980 
GPQKKIISSI KALETQSKNG PVPV 

« Hide

References

[1]"IL-1 beta alters the expression of the receptor tyrosine kinase gene r-EphA3 in neonatal rat cardiomyocytes."
Li Y.Y., McTiernan C.F., Feldman A.M.
Am. J. Physiol. 274:H331-H341(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U69278 mRNA. Translation: AAC06273.1.
PIRPT0186.
RefSeqNP_113752.1. NM_031564.1.
UniGeneRn.10713.

3D structure databases

ProteinModelPortalO08680.
SMRO08680. Positions 29-203, 614-907.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000043263.

PTM databases

PhosphoSiteO08680.

Proteomic databases

PaxDbO08680.
PRIDEO08680.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID29210.
KEGGrno:29210.
UCSCRGD:68389. rat.

Organism-specific databases

CTD2042.
RGD68389. Epha3.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233856.
HOVERGENHBG062180.
InParanoidO08680.
KOK05104.
PhylomeDBO08680.

Enzyme and pathway databases

BRENDA2.7.10.1. 5301.

Gene expression databases

GenevestigatorO08680.

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

NextBio608380.
PROO08680.

Entry information

Entry nameEPHA3_RAT
AccessionPrimary (citable) accession number: O08680
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 132 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