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P20827 (EFNA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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
Tumor necrosis factor alpha-induced protein 4
Short name=TNF alpha-induced protein 4

Cleaved into the following chain:

  1. Ephrin-A1, secreted form
Gene names
Name:EFNA1
Synonyms:EPLG1, LERK1, TNFAIP4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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.8 Ref.9

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. Ref.9 Ref.10

Subcellular location

Cell membrane; Lipid-anchorGPI-anchor Ref.7 Ref.9.

Ephrin-A1, secreted form: Secreted Ref.9.

Tissue specificity

Brain. Down-regulated in primary glioma tissues compared to the normal tissues. The soluble monomeric form is expressed in the glioblastoma multiforme (GBM) and breast cancer cells (at protein level). Ref.8

Induction

By TNF and IL1B/interleukin-1 beta.

Post-translational modification

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

Sequence similarities

Belongs to the ephrin family.

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

Ontologies

Keywords
   Biological processAngiogenesis
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseTumor suppressor
   DomainSignal
   PTMDisulfide bond
Glycoprotein
GPI-anchor
Lipoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of MAPK activity

Inferred from electronic annotation. Source: Ensembl

angiogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

aortic valve morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

axon guidance

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell migration

Inferred from direct assay PubMed 10655584. Source: UniProtKB

cell-cell signaling

Traceable author statement PubMed 8660976. Source: ProtInc

endocardial cushion to mesenchymal transition involved in heart valve formation

Inferred from sequence or structural similarity. Source: BHF-UCL

ephrin receptor signaling pathway

Inferred from direct assay PubMed 10655584. Source: UniProtKB

mitral valve morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of dendritic spine morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of epithelial to mesenchymal transition

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

notochord formation

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 10655584. Source: UniProtKB

regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

regulation of axonogenesis

Inferred from electronic annotation. Source: Ensembl

regulation of blood vessel endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

regulation of cell adhesion mediated by integrin

Inferred from direct assay PubMed 10655584. Source: UniProtKB

regulation of peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

substrate adhesion-dependent cell spreading

Inferred from direct assay PubMed 10655584. Source: UniProtKB

   Cellular_componentanchored component of plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Traceable author statement PubMed 8660976. Source: ProtInc

   Molecular_functionephrin receptor binding

Inferred from physical interaction PubMed 15777695. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.10PubMed 19573808. Source: IntAct

receptor binding

Traceable author statement PubMed 8660976. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

EPHA2P293177EBI-715194,EBI-702104

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P20827-1)

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 2 (identifier: P20827-2)

The sequence of this isoform differs from the canonical sequence as follows:
     131-152: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Ref.6
Chain19 – 182164Ephrin-A1
PRO_0000008353
Chain19 – ?Ephrin-A1, secreted formPRO_0000389630
Propeptide183 – 20523Removed in mature form Potential
PRO_0000008354

Regions

Domain19 – 151133Ephrin RBD

Amino acid modifications

Lipidation1821GPI-anchor amidated serine Potential
Glycosylation261N-linked (GlcNAc...) Potential
Disulfide bond51 ↔ 92 Ref.10 Ref.11
Disulfide bond80 ↔ 140 Ref.10 Ref.11

Natural variations

Alternative sequence131 – 15222Missing in isoform 2.
VSP_017543
Natural variant1591D → V. Ref.1 Ref.2 Ref.4 Ref.5
Corresponds to variant rs4745 [ dbSNP | Ensembl ].
VAR_014791

Experimental info

Sequence conflict1801G → A in AAH32698. Ref.5

Secondary structure

.......................... 205
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 30, 2005. Version 2.
Checksum: EFF026BF4C12461F

FASTA20523,787
        10         20         30         40         50         60 
MEFLWAPLLG LCCSLAAADR HTVFWNSSNP KFRNEDYTIH VQLNDYVDII CPHYEDHSVA 

        70         80         90        100        110        120 
DAAMEQYILY LVEHEEYQLC QPQSKDQVRW QCNRPSAKHG PEKLSEKFQR FTPFTLGKEF 

       130        140        150        160        170        180 
KEGHSYYYIS KPIHQHEDRC LRLKVTVSGK ITHSPQAHDN PQEKRLAADD PEVRVLHSIG 

       190        200 
HSAAPRLFPL AWTVLLLPLL LLQTP 

« Hide

Isoform 2 [UniParc].

Checksum: 8B9A70B6402577BD
Show »

FASTA18321,246

References

« Hide 'large scale' references
[1]"A novel immediate-early response gene of endothelium is induced by cytokines and encodes a secreted protein."
Holzman L.B., Marks R.M., Dixit V.M.
Mol. Cell. Biol. 10:5830-5838(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-159.
[2]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-159.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-159.
[5]"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] (ISOFORM 1), VARIANT VAL-159.
Tissue: Liver.
[6]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 19-33.
[7]"Ligands for the receptor tyrosine kinases hek and elk: isolation of cDNAs encoding a family of proteins."
Kozlosky C.J., Maraskovsky E., McGrew J.T., Vanden Bos T., Teepe M., Lyman S.D., Srinivasan S., Fletcher F.A., Gayle R.B. III, Cerretti D.P., Beckmann M.P.
Oncogene 10:299-306(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: GPI-ANCHOR.
[8]"Ephrin-A1 is a negative regulator in glioma through down-regulation of EphA2 and FAK."
Liu D.-P., Wang Y., Koeffler H.P., Xie D.
Int. J. Oncol. 30:865-871(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[9]"Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor."
Wykosky J., Palma E., Gibo D.M., Ringler S., Turner C.P., Debinski W.
Oncogene 27:7260-7273(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE.
[10]"Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex."
Himanen J.P., Goldgur Y., Miao H., Myshkin E., Guo H., Buck M., Nguyen M., Rajashankar K.R., Wang B., Nikolov D.B.
EMBO Rep. 10:722-728(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 19-147 IN COMPLEX WITH EPHA2, SUBUNIT, DISULFIDE BOND, GLYCOSYLATION AT ASN-26.
[11]"Ephrin A1 bound to the ligand binding domain of the human ephrin A2 (EPHA2) receptor protein kinase."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 19-171 IN COMPLEX WITH EPHA2, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M57730 mRNA. Translation: AAA58388.1.
CR457416 mRNA. Translation: CAG33697.1.
AL691442 Genomic DNA. Translation: CAI15319.1.
AL691442 Genomic DNA. Translation: CAI15320.1.
CH471121 Genomic DNA. Translation: EAW53131.1.
CH471121 Genomic DNA. Translation: EAW53132.1.
BC032698 mRNA. Translation: AAH32698.1.
BC095432 mRNA. Translation: AAH95432.1.
CCDSCCDS1091.1. [P20827-1]
CCDS1092.1. [P20827-2]
PIRA36377.
RefSeqNP_004419.2. NM_004428.2. [P20827-1]
NP_872626.1. NM_182685.1. [P20827-2]
UniGeneHs.516664.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3CZUX-ray2.65B17-171[»]
3HEIX-ray2.00B/D/F/H/J/L/N/P18-147[»]
3MBWX-ray2.81B17-171[»]
ProteinModelPortalP20827.
SMRP20827. Positions 18-147.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108262. 6 interactions.
DIPDIP-98N.
IntActP20827. 6 interactions.
MINTMINT-1393983.
STRING9606.ENSP00000357392.

PTM databases

PhosphoSiteP20827.

Polymorphism databases

DMDM73920206.

Proteomic databases

PaxDbP20827.
PRIDEP20827.

Protocols and materials databases

DNASU1942.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368406; ENSP00000357391; ENSG00000169242. [P20827-2]
ENST00000368407; ENSP00000357392; ENSG00000169242. [P20827-1]
GeneID1942.
KEGGhsa:1942.
UCSCuc001fhh.3. human. [P20827-1]
uc001fhi.3. human. [P20827-2]

Organism-specific databases

CTD1942.
GeneCardsGC01P155099.
H-InvDBHIX0116282.
HIX0116386.
HGNCHGNC:3221. EFNA1.
HPACAB032498.
MIM191164. gene.
neXtProtNX_P20827.
PharmGKBPA27656.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG296825.
HOGENOMHOG000234373.
HOVERGENHBG051447.
InParanoidP20827.
KOK05462.
OMAPIHHQED.
OrthoDBEOG70W3FD.
PhylomeDBP20827.

Enzyme and pathway databases

SignaLinkP20827.

Gene expression databases

BgeeP20827.
CleanExHS_EFNA1.
GenevestigatorP20827.

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

EvolutionaryTraceP20827.
GeneWikiEphrin_A1.
GenomeRNAi1942.
NextBio7865.
PROP20827.
SOURCESearch...

Entry information

Entry nameEFNA1_HUMAN
AccessionPrimary (citable) accession number: P20827
Secondary accession number(s): D3DV86 expand/collapse secondary AC list , Q5SR60, Q5SR61, Q6I9T9, Q8N578
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: August 30, 2005
Last modified: July 9, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM