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Protein

Ephrin-A1

Gene

Efna1

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

Functioni

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.3 Publications

GO - Molecular functioni

  1. ephrin receptor binding Source: MGI

GO - Biological processi

  1. activation of MAPK activity Source: MGI
  2. angiogenesis Source: UniProtKB-KW
  3. aortic valve morphogenesis Source: BHF-UCL
  4. axon guidance Source: GO_Central
  5. cell migration Source: MGI
  6. endocardial cushion to mesenchymal transition involved in heart valve formation Source: BHF-UCL
  7. ephrin receptor signaling pathway Source: UniProtKB
  8. mitral valve morphogenesis Source: BHF-UCL
  9. negative regulation of dendritic spine morphogenesis Source: UniProtKB
  10. negative regulation of epithelial to mesenchymal transition Source: BHF-UCL
  11. negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  12. neuron differentiation Source: MGI
  13. notochord formation Source: MGI
  14. positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  15. regulation of angiogenesis Source: UniProtKB
  16. regulation of axonogenesis Source: MGI
  17. regulation of blood vessel endothelial cell migration Source: UniProtKB
  18. regulation of cell adhesion mediated by integrin Source: MGI
  19. regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
  20. substrate adhesion-dependent cell spreading Source: MGI
Complete GO annotation...

Keywords - Biological processi

Angiogenesis

Enzyme and pathway databases

ReactomeiREACT_280640. EPHA-mediated growth cone collapse.
REACT_292566. EPH-Ephrin signaling.
REACT_314615. EPH-ephrin mediated repulsion of cells.

Names & Taxonomyi

Protein namesi
Recommended 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:
Gene namesi
Name:Efna1
Synonyms:Epgl1, Epl1, Lerk1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:103236. Efna1.

Subcellular locationi

Cell membrane By similarity; Lipid-anchorGPI-anchor By similarity

GO - Cellular componenti

  1. anchored component of plasma membrane Source: UniProtKB
  2. extracellular vesicular exosome Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Sequence AnalysisAdd
BLAST
Chaini18 – 182165Ephrin-A1PRO_0000008355Add
BLAST
Chaini18 – ?Ephrin-A1, secreted formPRO_0000389631
Propeptidei183 – 20523Removed in mature formSequence AnalysisPRO_0000008356Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi26 – 261N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi51 ↔ 92PROSITE-ProRule annotation
Disulfide bondi80 ↔ 140PROSITE-ProRule annotation
Lipidationi182 – 1821GPI-anchor amidated serineSequence Analysis

Post-translational modificationi

Undergoes proteolysis by a metalloprotease to give rise to a soluble monomeric form.By similarity
N-Glycosylation is required for binding to EPHA2 receptor and inducing its internalization.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiP52793.
PRIDEiP52793.

PTM databases

PhosphoSiteiP52793.

Expressioni

Gene expression databases

BgeeiP52793.
CleanExiMM_EFNA1.
ExpressionAtlasiP52793. baseline and differential.
GenevestigatoriP52793.

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
EPHA7Q153752EBI-5241529,EBI-1383428From a different organism.

Protein-protein interaction databases

BioGridi199389. 3 interactions.
IntActiP52793. 1 interaction.
STRINGi10090.ENSMUSP00000029566.

Structurei

3D structure databases

ProteinModelPortaliP52793.
SMRiP52793. Positions 18-147.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini18 – 161144Ephrin RBDPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the ephrin family.PROSITE-ProRule annotation
Contains 1 ephrin RBD (ephrin receptor-binding) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG296825.
GeneTreeiENSGT00390000015107.
HOGENOMiHOG000234373.
HOVERGENiHBG051447.
InParanoidiP52793.
KOiK05462.
OMAiPIHHQED.
OrthoDBiEOG70W3FD.
PhylomeDBiP52793.

Family and domain databases

Gene3Di2.60.40.420. 1 hit.
InterProiIPR008972. Cupredoxin.
IPR001799. Ephrin.
IPR019765. Ephrin_CS.
[Graphical view]
PANTHERiPTHR11304. PTHR11304. 1 hit.
PfamiPF00812. Ephrin. 1 hit.
[Graphical view]
PRINTSiPR01347. EPHRIN.
ProDomiPD002533. Ephrin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF49503. SSF49503. 1 hit.
PROSITEiPS01299. EPHRIN_RBD_1. 1 hit.
PS51551. EPHRIN_RBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P52793-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEFLWAPLLG LCCSLAAADR HIVFWNSSNP KFREEDYTVH VQLNDYLDII
60 70 80 90 100
CPHYEDDSVA DAAMERYTLY MVEHQEYVAC QPQSKDQVRW NCNRPSAKHG
110 120 130 140 150
PEKLSEKFQR FTPFILGKEF KEGHSYYYIS KPIYHQESQC LKLKVTVNGK
160 170 180 190 200
ITHNPQAHVN PQEKRLQADD PEVQVLHSIG YSAAPRLFPL VWAVLLLPLL

LLQSQ
Length:205
Mass (Da):23,802
Last modified:September 30, 1996 - v1
Checksum:i5A8F3A6E2091E868
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti74 – 741H → Y in BAA07344 (PubMed:7675446).Curated
Sequence conflicti79 – 791A → T in BAA07344 (PubMed:7675446).Curated
Sequence conflicti81 – 811Q → E in BAA07344 (PubMed:7675446).Curated
Sequence conflicti91 – 911N → K in BAA07344 (PubMed:7675446).Curated
Sequence conflicti94 – 941R → Q in BAA07344 (PubMed:7675446).Curated
Sequence conflicti112 – 1121T → S in BAA07344 (PubMed:7675446).Curated
Sequence conflicti115 – 1151I → T in BAA07344 (PubMed:7675446).Curated
Sequence conflicti138 – 1381S → T in BAA07344 (PubMed:7675446).Curated
Sequence conflicti154 – 1541N → S in BAA07344 (PubMed:7675446).Curated
Sequence conflicti156 – 1561Q → H in BAA07344 (PubMed:7675446).Curated
Sequence conflicti159 – 1591V → A in BAA07344 (PubMed:7675446).Curated
Sequence conflicti181 – 1811Y → H in BAA07344 (PubMed:7675446).Curated
Sequence conflicti204 – 2041S → T in BAA07344 (PubMed:7675446).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D38146 mRNA. Translation: BAA07344.1.
U26188 mRNA. Translation: AAA67563.1.
U90662 mRNA. Translation: AAB50237.1.
BC002046 mRNA. Translation: AAH02046.1.
CCDSiCCDS17501.1.
RefSeqiNP_034237.3. NM_010107.4.
UniGeneiMm.15675.

Genome annotation databases

EnsembliENSMUST00000029566; ENSMUSP00000029566; ENSMUSG00000027954.
GeneIDi13636.
KEGGimmu:13636.
UCSCiuc008pyo.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D38146 mRNA. Translation: BAA07344.1.
U26188 mRNA. Translation: AAA67563.1.
U90662 mRNA. Translation: AAB50237.1.
BC002046 mRNA. Translation: AAH02046.1.
CCDSiCCDS17501.1.
RefSeqiNP_034237.3. NM_010107.4.
UniGeneiMm.15675.

3D structure databases

ProteinModelPortaliP52793.
SMRiP52793. Positions 18-147.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199389. 3 interactions.
IntActiP52793. 1 interaction.
STRINGi10090.ENSMUSP00000029566.

PTM databases

PhosphoSiteiP52793.

Proteomic databases

PaxDbiP52793.
PRIDEiP52793.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029566; ENSMUSP00000029566; ENSMUSG00000027954.
GeneIDi13636.
KEGGimmu:13636.
UCSCiuc008pyo.2. mouse.

Organism-specific databases

CTDi1942.
MGIiMGI:103236. Efna1.

Phylogenomic databases

eggNOGiNOG296825.
GeneTreeiENSGT00390000015107.
HOGENOMiHOG000234373.
HOVERGENiHBG051447.
InParanoidiP52793.
KOiK05462.
OMAiPIHHQED.
OrthoDBiEOG70W3FD.
PhylomeDBiP52793.

Enzyme and pathway databases

ReactomeiREACT_280640. EPHA-mediated growth cone collapse.
REACT_292566. EPH-Ephrin signaling.
REACT_314615. EPH-ephrin mediated repulsion of cells.

Miscellaneous databases

NextBioi284320.
PROiP52793.
SOURCEiSearch...

Gene expression databases

BgeeiP52793.
CleanExiMM_EFNA1.
ExpressionAtlasiP52793. baseline and differential.
GenevestigatoriP52793.

Family and domain databases

Gene3Di2.60.40.420. 1 hit.
InterProiIPR008972. Cupredoxin.
IPR001799. Ephrin.
IPR019765. Ephrin_CS.
[Graphical view]
PANTHERiPTHR11304. PTHR11304. 1 hit.
PfamiPF00812. Ephrin. 1 hit.
[Graphical view]
PRINTSiPR01347. EPHRIN.
ProDomiPD002533. Ephrin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF49503. SSF49503. 1 hit.
PROSITEiPS01299. EPHRIN_RBD_1. 1 hit.
PS51551. EPHRIN_RBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and expression of rat and mouse B61 gene: implications on organogenesis."
    Takahashi H., Ikeda T.
    Oncogene 11:879-883(1994) [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 (APR-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(1995) [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(2003) [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(2005) [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(2006) [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(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiEFNA1_MOUSE
AccessioniPrimary (citable) accession number: P52793
Secondary accession number(s): P97331
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 30, 1996
Last sequence update: September 30, 1996
Last modified: March 31, 2015
This is version 117 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. 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.