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P52793 (EFNA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ephrin-A1
Alternative name(s):
EPH-related receptor tyrosine kinase ligand 1
Short name=LERK-1
Immediate early response protein B61

Cleaved into the following chain:

  1. Ephrin-A1, secreted form
Gene names
Name:Efna1
Synonyms:Epgl1, Epl1, Lerk1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length205 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Plays an important role in angiogenesis and tumor neovascularization. The recruitment of VAV2, VAV3 and PI3-kinase p85 subunit by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly. Exerts anti-oncogenic effects in tumor cells through activation and down-regulation of EPHA2. Activates EPHA2 by inducing tyrosine phosphorylation which leads to its internalization and degradation. Acts as a negative regulator in the tumorigenesis of gliomas by down-regulating EPHA2 and FAK. Can evoke collapse of embryonic neuronal growth cone and regulates dendritic spine morphogenesis. Ref.5 Ref.6 Ref.7

Subunit structure

Monomer. Homodimer. Forms heterodimers with EPHA2. Binds to the receptor tyrosine kinases EPHA2, EPHA3, EPHA4, EPHA5, EPHA6 and EPHA7. Also binds with low affinity to EPHA1 By similarity.

Subcellular location

Cell membrane; Lipid-anchorGPI-anchor By similarity.

Ephrin-A1, secreted form: Secreted By similarity.

Post-translational modification

Undergoes proteolysis by a metalloprotease to give rise to a soluble monomeric form By similarity.

Sequence similarities

Belongs to the ephrin family.

Contains 1 ephrin RBD (ephrin receptor-binding) domain.

Ontologies

Keywords
   Biological processAngiogenesis
   Cellular componentCell membrane
Membrane
Secreted
   DiseaseTumor suppressor
   DomainSignal
   PTMDisulfide bond
Glycoprotein
GPI-anchor
Lipoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of MAPK activity

Inferred from direct assay PubMed 15145949. Source: MGI

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

aortic valve morphogenesis

Inferred from mutant phenotype PubMed 20960543. Source: BHF-UCL

axon guidance

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell migration

Inferred from electronic annotation. Source: Ensembl

endocardial cushion to mesenchymal transition involved in heart valve formation

Inferred from mutant phenotype PubMed 20960543. Source: BHF-UCL

ephrin receptor signaling pathway

Inferred from direct assay Ref.6. Source: UniProtKB

mitral valve morphogenesis

Inferred from mutant phenotype PubMed 20960543. Source: BHF-UCL

negative regulation of dendritic spine morphogenesis

Inferred from direct assay Ref.6. Source: UniProtKB

negative regulation of epithelial to mesenchymal transition

Inferred from mutant phenotype PubMed 20960543. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 20960543. Source: BHF-UCL

neuron differentiation

Inferred from direct assay PubMed 15145949. Source: MGI

notochord formation

Inferred from genetic interaction PubMed 11287184. Source: MGI

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of angiogenesis

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of axonogenesis

Inferred from direct assay PubMed 14988728. Source: MGI

regulation of blood vessel endothelial cell migration

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of cell adhesion mediated by integrin

Inferred from electronic annotation. Source: Ensembl

regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.6. Source: UniProtKB

substrate adhesion-dependent cell spreading

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentanchored component of plasma membrane

Inferred from direct assay PubMed 18794797. Source: UniProtKB

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionephrin receptor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein binding

Inferred from physical interaction PubMed 22036564. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

EPHA7Q153752EBI-5241529,EBI-1383428From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Chain18 – 182165Ephrin-A1
PRO_0000008355
Chain18 – ?Ephrin-A1, secreted formPRO_0000389631
Propeptide183 – 20523Removed in mature form Potential
PRO_0000008356

Regions

Domain18 – 161144Ephrin RBD

Amino acid modifications

Lipidation1821GPI-anchor amidated serine Potential
Glycosylation261N-linked (GlcNAc...) Potential
Disulfide bond51 ↔ 92 By similarity
Disulfide bond80 ↔ 140 By similarity

Experimental info

Sequence conflict741H → Y in BAA07344. Ref.1
Sequence conflict791A → T in BAA07344. Ref.1
Sequence conflict811Q → E in BAA07344. Ref.1
Sequence conflict911N → K in BAA07344. Ref.1
Sequence conflict941R → Q in BAA07344. Ref.1
Sequence conflict1121T → S in BAA07344. Ref.1
Sequence conflict1151I → T in BAA07344. Ref.1
Sequence conflict1381S → T in BAA07344. Ref.1
Sequence conflict1541N → S in BAA07344. Ref.1
Sequence conflict1561Q → H in BAA07344. Ref.1
Sequence conflict1591V → A in BAA07344. Ref.1
Sequence conflict1811Y → H in BAA07344. Ref.1
Sequence conflict2041S → T in BAA07344. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P52793 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 5A8F3A6E2091E868

FASTA20523,802
        10         20         30         40         50         60 
MEFLWAPLLG LCCSLAAADR HIVFWNSSNP KFREEDYTVH VQLNDYLDII CPHYEDDSVA 

        70         80         90        100        110        120 
DAAMERYTLY MVEHQEYVAC QPQSKDQVRW NCNRPSAKHG PEKLSEKFQR FTPFILGKEF 

       130        140        150        160        170        180 
KEGHSYYYIS KPIYHQESQC LKLKVTVNGK ITHNPQAHVN PQEKRLQADD PEVQVLHSIG 

       190        200 
YSAAPRLFPL VWAVLLLPLL LLQSQ 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and expression of rat and mouse B61 gene: implications on organogenesis."
Takahashi H., Ikeda T.
Oncogene 11:879-883(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: ICR.
[2]Morris J.C., Ciarletta A., Morris G.E., Giannotti J., Caruso A., Hammett D.J., Finnerty H., Turner K., Wood C.R.
Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
[3]"Distinct and overlapping expression patterns of ligands for Eph-related receptor tyrosine kinases during mouse embryogenesis."
Flenniken A.M., Gale N.W., Yancopoulos G.D., Wilkinson D.G.
Dev. Biol. 179:382-401(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Mammary gland.
[5]"Essential role of Vav family guanine nucleotide exchange factors in EphA receptor-mediated angiogenesis."
Hunter S.G., Zhuang G., Brantley-Sieders D.M., Swat W., Cowan C.W., Chen J.
Mol. Cell. Biol. 26:4830-4842(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism."
Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O., Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y.
Nat. Neurosci. 10:67-76(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DENDRITIC SPINE MORPHOGENESIS.
[7]"Identification and functional analysis of phosphorylated tyrosine residues within EphA2 receptor tyrosine kinase."
Fang W.B., Brantley-Sieders D.M., Hwang Y., Ham A.-J.L., Chen J.
J. Biol. Chem. 283:16017-16026(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D38146 mRNA. Translation: BAA07344.1.
U26188 mRNA. Translation: AAA67563.1.
U90662 mRNA. Translation: AAB50237.1.
BC002046 mRNA. Translation: AAH02046.1.
CCDSCCDS17501.1.
RefSeqNP_034237.3. NM_010107.4.
UniGeneMm.15675.

3D structure databases

ProteinModelPortalP52793.
SMRP52793. Positions 18-147.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199389. 3 interactions.
IntActP52793. 1 interaction.
STRING10090.ENSMUSP00000029566.

PTM databases

PhosphoSiteP52793.

Proteomic databases

PaxDbP52793.
PRIDEP52793.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000029566; ENSMUSP00000029566; ENSMUSG00000027954.
GeneID13636.
KEGGmmu:13636.
UCSCuc008pyo.2. mouse.

Organism-specific databases

CTD1942.
MGIMGI:103236. Efna1.

Phylogenomic databases

eggNOGNOG296825.
GeneTreeENSGT00390000015107.
HOGENOMHOG000234373.
HOVERGENHBG051447.
InParanoidP52793.
KOK05462.
OMAPIHHQED.
OrthoDBEOG70W3FD.
PhylomeDBP52793.

Gene expression databases

ArrayExpressP52793.
BgeeP52793.
CleanExMM_EFNA1.
GenevestigatorP52793.

Family and domain databases

Gene3D2.60.40.420. 1 hit.
InterProIPR008972. Cupredoxin.
IPR001799. Ephrin.
IPR019765. Ephrin_CS.
[Graphical view]
PANTHERPTHR11304. PTHR11304. 1 hit.
PfamPF00812. Ephrin. 1 hit.
[Graphical view]
PRINTSPR01347. EPHRIN.
ProDomPD002533. Ephrin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMSSF49503. SSF49503. 1 hit.
PROSITEPS01299. EPHRIN_RBD_1. 1 hit.
PS51551. EPHRIN_RBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio284320.
PROP52793.
SOURCESearch...

Entry information

Entry nameEFNA1_MOUSE
AccessionPrimary (citable) accession number: P52793
Secondary accession number(s): P97331
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 111 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

MGD cross-references

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