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P20827

- EFNA1_HUMAN

UniProt

P20827 - EFNA1_HUMAN

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Protein

Ephrin-A1

Gene
EFNA1, EPLG1, LERK1, TNFAIP4
Organism
Homo sapiens (Human)
Status
Reviewed - 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.2 Publications

GO - Molecular functioni

  1. ephrin receptor binding Source: UniProtKB
  2. protein binding Source: IntAct
  3. receptor binding Source: ProtInc

GO - Biological processi

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

Keywords - Biological processi

Angiogenesis

Enzyme and pathway databases

SignaLinkiP20827.

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
Tumor necrosis factor alpha-induced protein 4
Short name:
TNF alpha-induced protein 4
Cleaved into the following chain:
Gene namesi
Name:EFNA1
Synonyms:EPLG1, LERK1, TNFAIP4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:3221. EFNA1.

Subcellular locationi

Cell membrane; Lipid-anchorGPI-anchor 2 Publications
Chain Ephrin-A1, secreted form : Secreted 1 Publication

GO - Cellular componenti

  1. anchored component of plasma membrane Source: RefGenome
  2. extracellular vesicular exosome Source: UniProt
  3. integral component of plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

PharmGKBiPA27656.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 18181 PublicationAdd
BLAST
Chaini19 – 182164Ephrin-A1PRO_0000008353Add
BLAST
Chaini19 – ?Ephrin-A1, secreted formPRO_0000389630
Propeptidei183 – 20523Removed in mature form Reviewed predictionPRO_0000008354Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi26 – 261N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi51 ↔ 922 Publications
Disulfide bondi80 ↔ 1402 Publications
Lipidationi182 – 1821GPI-anchor amidated serine Reviewed prediction

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiP20827.
PRIDEiP20827.

PTM databases

PhosphoSiteiP20827.

Expressioni

Tissue specificityi

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).1 Publication

Inductioni

By TNF and IL1B/interleukin-1 beta.

Gene expression databases

BgeeiP20827.
CleanExiHS_EFNA1.
GenevestigatoriP20827.

Organism-specific databases

HPAiCAB032498.

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 EPHA1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EPHA2P293177EBI-715194,EBI-702104

Protein-protein interaction databases

BioGridi108262. 6 interactions.
DIPiDIP-98N.
IntActiP20827. 6 interactions.
MINTiMINT-1393983.
STRINGi9606.ENSP00000357392.

Structurei

Secondary structure

1
205
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi20 – 245
Helixi30 – 323
Beta strandi38 – 414
Beta strandi46 – 505
Helixi61 – 633
Beta strandi67 – 726
Helixi74 – 796
Helixi85 – 873
Beta strandi88 – 925
Beta strandi98 – 1003
Beta strandi103 – 1075
Beta strandi125 – 13410
Beta strandi142 – 1476

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3CZUX-ray2.65B17-171[»]
3HEIX-ray2.00B/D/F/H/J/L/N/P18-147[»]
3MBWX-ray2.81B17-171[»]
ProteinModelPortaliP20827.
SMRiP20827. Positions 18-147.

Miscellaneous databases

EvolutionaryTraceiP20827.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini19 – 151133Ephrin RBDAdd
BLAST

Sequence similaritiesi

Belongs to the ephrin family.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG296825.
HOGENOMiHOG000234373.
HOVERGENiHBG051447.
InParanoidiP20827.
KOiK05462.
OMAiPIHHQED.
OrthoDBiEOG70W3FD.
PhylomeDBiP20827.

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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P20827-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MEFLWAPLLG LCCSLAAADR HTVFWNSSNP KFRNEDYTIH VQLNDYVDII    50
CPHYEDHSVA DAAMEQYILY LVEHEEYQLC QPQSKDQVRW QCNRPSAKHG 100
PEKLSEKFQR FTPFTLGKEF KEGHSYYYIS KPIHQHEDRC LRLKVTVSGK 150
ITHSPQAHDN PQEKRLAADD PEVRVLHSIG HSAAPRLFPL AWTVLLLPLL 200
LLQTP 205
Length:205
Mass (Da):23,787
Last modified:August 30, 2005 - v2
Checksum:iEFF026BF4C12461F
GO
Isoform 2 (identifier: P20827-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     131-152: Missing.

Note: No experimental confirmation available.

Show »
Length:183
Mass (Da):21,246
Checksum:i8B9A70B6402577BD
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti159 – 1591D → V.4 Publications
Corresponds to variant rs4745 [ dbSNP | Ensembl ].
VAR_014791

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei131 – 15222Missing in isoform 2. VSP_017543Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti180 – 1801G → A in AAH32698. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS1091.1. [P20827-1]
CCDS1092.1. [P20827-2]
PIRiA36377.
RefSeqiNP_004419.2. NM_004428.2. [P20827-1]
NP_872626.1. NM_182685.1. [P20827-2]
UniGeneiHs.516664.

Genome annotation databases

EnsembliENST00000368406; ENSP00000357391; ENSG00000169242. [P20827-2]
ENST00000368407; ENSP00000357392; ENSG00000169242. [P20827-1]
GeneIDi1942.
KEGGihsa:1942.
UCSCiuc001fhh.3. human. [P20827-1]
uc001fhi.3. human. [P20827-2]

Polymorphism databases

DMDMi73920206.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS1091.1. [P20827-1 ]
CCDS1092.1. [P20827-2 ]
PIRi A36377.
RefSeqi NP_004419.2. NM_004428.2. [P20827-1 ]
NP_872626.1. NM_182685.1. [P20827-2 ]
UniGenei Hs.516664.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3CZU X-ray 2.65 B 17-171 [» ]
3HEI X-ray 2.00 B/D/F/H/J/L/N/P 18-147 [» ]
3MBW X-ray 2.81 B 17-171 [» ]
ProteinModelPortali P20827.
SMRi P20827. Positions 18-147.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108262. 6 interactions.
DIPi DIP-98N.
IntActi P20827. 6 interactions.
MINTi MINT-1393983.
STRINGi 9606.ENSP00000357392.

PTM databases

PhosphoSitei P20827.

Polymorphism databases

DMDMi 73920206.

Proteomic databases

PaxDbi P20827.
PRIDEi P20827.

Protocols and materials databases

DNASUi 1942.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000368406 ; ENSP00000357391 ; ENSG00000169242 . [P20827-2 ]
ENST00000368407 ; ENSP00000357392 ; ENSG00000169242 . [P20827-1 ]
GeneIDi 1942.
KEGGi hsa:1942.
UCSCi uc001fhh.3. human. [P20827-1 ]
uc001fhi.3. human. [P20827-2 ]

Organism-specific databases

CTDi 1942.
GeneCardsi GC01P155099.
H-InvDB HIX0116282.
HIX0116386.
HGNCi HGNC:3221. EFNA1.
HPAi CAB032498.
MIMi 191164. gene.
neXtProti NX_P20827.
PharmGKBi PA27656.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG296825.
HOGENOMi HOG000234373.
HOVERGENi HBG051447.
InParanoidi P20827.
KOi K05462.
OMAi PIHHQED.
OrthoDBi EOG70W3FD.
PhylomeDBi P20827.

Enzyme and pathway databases

SignaLinki P20827.

Miscellaneous databases

EvolutionaryTracei P20827.
GeneWikii Ephrin_A1.
GenomeRNAii 1942.
NextBioi 7865.
PROi P20827.
SOURCEi Search...

Gene expression databases

Bgeei P20827.
CleanExi HS_EFNA1.
Genevestigatori P20827.

Family and domain databases

Gene3Di 2.60.40.420. 1 hit.
InterProi IPR008972. Cupredoxin.
IPR001799. Ephrin.
IPR019765. Ephrin_CS.
[Graphical view ]
PANTHERi PTHR11304. PTHR11304. 1 hit.
Pfami PF00812. Ephrin. 1 hit.
[Graphical view ]
PRINTSi PR01347. EPHRIN.
ProDomi PD002533. Ephrin. 1 hit.
[Graphical view ] [Entries sharing at least one domain ]
SUPFAMi SSF49503. SSF49503. 1 hit.
PROSITEi PS01299. EPHRIN_RBD_1. 1 hit.
PS51551. EPHRIN_RBD_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiEFNA1_HUMAN
AccessioniPrimary (citable) accession number: P20827
Secondary accession number(s): D3DV86
, Q5SR60, Q5SR61, Q6I9T9, Q8N578
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: August 30, 2005
Last modified: September 3, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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