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Q07496 (EPHA4_CHICK) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Ephrin type-A receptor 4
EC=2.7.10.1
Alternative name(s):
EPH-like kinase 8
Short name=EK8
Short name=cEK8
Gene names
Name:EPHA4
Synonyms:CEK8
OrganismGallus gallus (Chicken)
Taxonomic identifier9031 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galliformes › Phasianidae › Phasianinae › Gallus

Protein attributes

Sequence length986 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 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, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections By similarity.

Catalytic activity

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

Subunit structure

Interacts with the src family kinase, p59-Fyn, through the major phosphorylation site at position Tyr-602 By similarity. Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases. Ref.3

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity. Early endosome By similarity. Note: Clustered upon activation and targeted to early endosome By similarity.

Tissue specificity

Expressed at high levels in brain, with expression also detected in the kidney, lung, muscle and thymus.

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
   Biological processCell adhesion
Neurogenesis
   Cellular componentCell membrane
Endosome
Membrane
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological processcell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of Rho guanyl-nucleotide exchange factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of Rac GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of Rap GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular componentearly endosome membrane

Inferred from sequence or structural similarity. Source: UniProtKB

integral to plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DH domain binding

Inferred from sequence or structural similarity. Source: UniProtKB

GPI-linked ephrin receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

transmembrane-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 – 1919 Potential
Chain20 – 986967Ephrin type-A receptor 4
PRO_0000016809

Regions

Topological domain20 – 547528Extracellular Potential
Transmembrane548 – 56922Helical; Potential
Topological domain570 – 986417Cytoplasmic Potential
Domain30 – 209180Eph LBD
Domain328 – 431104Fibronectin type-III 1
Domain441 – 53494Fibronectin type-III 2
Domain621 – 882262Protein kinase
Domain911 – 97565SAM
Nucleotide binding627 – 6359ATP By similarity
Motif984 – 9863PDZ-binding Potential
Compositional bias191 – 325135Cys-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 residue7791Phosphotyrosine; by autocatalysis Potential
Modified residue9281Phosphotyrosine; by autocatalysis Potential
Glycosylation2351N-linked (GlcNAc...) Potential
Glycosylation3401N-linked (GlcNAc...) Potential
Glycosylation4081N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict1381R → G in CAA79509. Ref.2
Sequence conflict4871S → T in CAA79509. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q07496 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: BD88C2A5BD840A0F

FASTA986109,483
        10         20         30         40         50         60 
MAGVPVGALL PLLVGVCGAV TGSRVYPANE VTLLDSRSVQ GELGWIASPL EGGWEEVSIM 

        70         80         90        100        110        120 
DEKNTPIRTY QVCNVMEPSQ NNWLRTDWIP REGAQRVYIE IKFTLRDCNS LPGVMGTCKE 

       130        140        150        160        170        180 
TFNLYYYESN NDKERFIRES QFAKIDTIAA DESFTQVDIG DRIMKLNTEV RDVGPLSKKG 

       190        200        210        220        230        240 
FYLAFQDVGA CIALVSVRVF YKKCPLTVRN LAQFPDTITG ADTSSLVEVR GSCVNNSEEK 

       250        260        270        280        290        300 
DVPKMYCGAD GEWLVPIGNC LCNAGYEERN GECQACKIGY YKALSTDVAC AKCPPHSYSI 

       310        320        330        340        350        360 
WEGSTSCTCD RGFFRAENDA ASMPCTRPPS APQNLISNVN ETSVNLEWSA PQNKGGRDDI 

       370        380        390        400        410        420 
SYNVVCKRCG AGEPSHCRSC GSGVHFSPQQ NGLKTTKVSI TDLLAHTNYT FEVWAVNGVS 

       430        440        450        460        470        480 
KHNPSQDQAV SVTVTTNQAA PSPIALIQAK EITRHSVALA WLEPDRPNGV ILEYEVKYYE 

       490        500        510        520        530        540 
KDQNERSYRI VKTASRNTDI KGLNPLTSYV FHVRARTAAG YGDFSGPFEF TTNTVPSPII 

       550        560        570        580        590        600 
GDGTNPTVLL VSVAGSVVLV VILIAAFVIS RRRSKYSKAK QEADEEKHLN QGVRTYVDPF 

       610        620        630        640        650        660 
TYEDPNQAVR EFAKEIDASC IKIEKVIGVG EFGEVCSGRL KVPGKREICV AIKTLKAGYT 

       670        680        690        700        710        720 
DKQRRDFLSE ASIMGQFDHP NIIHLEGVVT KCKPVMIITE YMENGSLDAF LRKNDGRFTV 

       730        740        750        760        770        780 
IQLVGMLRGI GSGMKYLSDM SYVHRDLAAR NILVNSNLVC KVSDFGMSRV LEDDPEAAYT 

       790        800        810        820        830        840 
TRGGKIPIRW TAPEAIAYRK FTSASDVWSY GIVMWEVMSY GERPYWDMSN QDVIKAIEEG 

       850        860        870        880        890        900 
YRLPPPMDCP IALHQLMLDC WQKERSDRPK FGQIVNMLDK LIRNPNSLKR TGSESSRPST 

       910        920        930        940        950        960 
ALLDPSSPEF SAVVSVSDWL QAIKMERYKD NFTAAGYTTL EAVVHMNQDD LARIGITAIT 

       970        980 
HQNKILSSVQ AMRSQMQQMH GRMVPV

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References

[1]"The receptor tyrosine kinase, Cek8, is transiently expressed on subtypes of motoneurons in the spinal cord during development."
Ohta K., Nakamura M., Hirokawa K., Tanaka S., Iwama A., Suda T., Ando M., Tanaka H.
Mech. Dev. 54:59-69(1996) [PubMed: 8808406] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Spinal cord.
[2]"Five novel avian Eph-related tyrosine kinases are differentially expressed."
Sajjadi F.G., Pasquale E.B.
Oncogene 8:1807-1813(1993) [PubMed: 8510926] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 138-986.
Tissue: Embryo.
[3]"The EphA4 receptor regulates neuronal morphology through SPAR-mediated inactivation of Rap GTPases."
Richter M., Murai K.K., Bourgin C., Pak D.T., Pasquale E.B.
J. Neurosci. 27:14205-14215(2007) [PubMed: 18094260] [Abstract]
Cited for: INTERACTION WITH SIPA1L1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		D38174 mRNA. Translation: BAA07373.1.
Z19059 mRNA. Translation: CAA79509.1.
IPIIPI00600669.
PIRI50617.
RefSeqNP_990112.1. NM_204781.1.
UniGeneGga.304.

3D structure databases

ProteinModelPortalQ07496.
SMRQ07496. Positions 30-205, 595-904, 910-981.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ07496.

Proteomic databases

PRIDEQ07496.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSGALT00000008440; ENSGALP00000008426; ENSGALG00000005256.
GeneID395559.
KEGGgga:395559.

Organism-specific databases

CTD2043.

Phylogenomic databases

eggNOGveNOG10190.
HOGENOMHBG755340.
HOVERGENHBG062180.
InParanoidQ07496.
OMAITAVTHQ.
OrthoDBEOG48SGS9.

Enzyme and pathway databases

BRENDA2.7.10.1. 1306.

Family and domain databases

InterProIPR001090. Ephrin_rcpt_lig-bd.
IPR003961. Fibronectin_type3.
IPR008979. Galactose-bd-like.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
IPR001245. Ser-Thr/Tyr_kinase.
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]
Gene3DG3DSA:2.60.40.10. Ig-like_fold. 2 hits.
G3DSA:1.10.150.50. SAM_type. 1 hit.
KOK05105.
PfamPF01404. 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]
SUPFAMSSF49265. FN_III-like. 2 hits.
SSF49785. Gal_bind_like. 1 hit.
SSF56112. Kinase_like. 1 hit.
SSF47769. SAM_homology. 1 hit.
PROSITEPS01186. EGF_2. 1 hit. Uncertain.
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...

Entry information

Entry nameEPHA4_CHICK
AccessionPrimary (citable) accession number: Q07496
Secondary accession number(s): Q90772
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: December 14, 2011
This is version 111 of the entry and version 2 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

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents