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P52803 (EFNA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ephrin-A5
Alternative name(s):
AL-1
EPH-related receptor tyrosine kinase ligand 7
Short name=LERK-7
Gene names
Name:EFNA5
Synonyms:EPLG7, LERK7
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length228 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. 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. Induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate receptor. This signaling event requires the activity of the Fyn tyrosine kinase. Activates the EPHA3 receptor to regulate cell-cell adhesion and cytoskeletal organization. With the receptor EPHA2 may regulate lens fiber cells shape and interactions and be important for lens transparency maintenance. May function actively to stimulate axon fasciculation. The interaction of EFNA5 with EPHA5 also mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion. Cognate/functional ligand for EPHA7, their interaction regulates brain development modulating cell-cell adhesion and repulsion. Ref.4 Ref.5

Subunit structure

Binds to EPHB2. Interacts with EPHA8; activates EPHA8 By similarity. Binds to the receptor tyrosine kinases EPHA2, EPHA3 and EPHB1. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function. Ref.6

Subcellular location

Cell membrane; Lipid-anchorGPI-anchor. Membranecaveola; Lipid-anchorGPI-anchor. Note: Compartmentalized in discrete caveolae-like membrane microdomains. Ref.5

Sequence similarities

Belongs to the ephrin family.

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

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
GPI-anchor
Lipoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaxon guidance

Inferred from Biological aspect of Ancestor. Source: RefGenome

ephrin receptor signaling pathway

Inferred from direct assay Ref.5. Source: UniProtKB

nervous system development

Traceable author statement Ref.2. Source: ProtInc

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of Rac GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of Rho GTPase activity

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of actin cytoskeleton organization

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of cell-cell adhesion

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of focal adhesion assembly

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of microtubule cytoskeleton organization

Inferred from direct assay Ref.5. Source: UniProtKB

retinal ganglion cell axon guidance

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentanchored component of external side of plasma membrane

Inferred from direct assay Ref.5. Source: UniProtKB

caveola

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionchemorepellent activity

Inferred from electronic annotation. Source: Ensembl

ephrin receptor binding

Inferred from physical interaction Ref.5PubMed 15777695. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 203183Ephrin-A5
PRO_0000008377
Propeptide204 – 22825Removed in mature form Potential
PRO_0000008378

Regions

Domain29 – 162134Ephrin RBD

Amino acid modifications

Lipidation2031GPI-anchor amidated asparagine Potential
Glycosylation371N-linked (GlcNAc...) Ref.7
Disulfide bond62 ↔ 102
Disulfide bond90 ↔ 151

Natural variations

Natural variant551N → K.
Corresponds to variant rs469062 [ dbSNP | Ensembl ].
VAR_012035

Secondary structure

........................... 228
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P52803 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 6893B1CCACFF3F57

FASTA22826,297
        10         20         30         40         50         60 
MLHVEMLTLV FLVLWMCVFS QDPGSKAVAD RYAVYWNSSN PRFQRGDYHI DVCINDYLDV 

        70         80         90        100        110        120 
FCPHYEDSVP EDKTERYVLY MVNFDGYSAC DHTSKGFKRW ECNRPHSPNG PLKFSEKFQL 

       130        140        150        160        170        180 
FTPFSLGFEF RPGREYFYIS SAIPDNGRRS CLKLKVFVRP TNSCMKTIGV HDRVFDVNDK 

       190        200        210        220 
VENSLEPADD TVHESAEPSR GENAAQTPRI PSRLLAILLF LLAMLLTL 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of AL-1, a ligand for an Eph-related tyrosine kinase receptor involved in axon bundle formation."
Winslow J.W., Moran P., Valverde J., Shih A., Yuan J.Q., Wong S.C., Tsai S.P., Goddard A., Henzel W.J., Hefti F., Beck K.D., Caras I.W.
Neuron 14:973-981(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"LERK-7: a ligand of the Eph-related kinases is developmentally regulated in the brain."
Kozlosky C.J., Vanden Bos T., Park L.S., Cerretti D.P., Carpenter M.K.
Cytokine 9:540-549(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"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].
Tissue: Brain.
[4]"Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion."
Davy A., Gale N.W., Murray E.W., Klinghoffer R.A., Soriano P., Feuerstein C., Robbins S.M.
Genes Dev. 13:3125-3135(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling."
Lawrenson I.D., Wimmer-Kleikamp S.H., Lock P., Schoenwaelder S.M., Down M., Boyd A.W., Alewood P.F., Lackmann M.
J. Cell Sci. 115:1059-1072(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL-CELL ADHESION, EPHA3-BINDING, SUBCELLULAR LOCATION.
[6]"Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans."
Janes P.W., Saha N., Barton W.A., Kolev M.V., Wimmer-Kleikamp S.H., Nievergall E., Blobel C.P., Himanen J.P., Lackmann M., Nikolov D.B.
Cell 123:291-304(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH ADAM10 AND EPHA3.
[7]"Crystal structure of the human ephrin-A5 ectodomain."
Nikolov D.B., Li C., Lackmann M., Jeffrey P., Himanen J.P.
Protein Sci. 16:996-1000(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 27-189, GLYCOSYLATION AT ASN-37.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U26403 mRNA. Translation: AAB60377.1.
BC075054 mRNA. Translation: AAH75054.1.
BC075055 mRNA. Translation: AAH75055.1.
PIRI58170.
RefSeqNP_001953.1. NM_001962.2.
UniGeneHs.288741.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2X11X-ray4.83B27-166[»]
3MX0X-ray3.51B/D28-165[»]
4BK5X-ray4.00C27-166[»]
4BKAX-ray5.30C27-166[»]
4M4RX-ray3.13B/D/F/H27-165[»]
ProteinModelPortalP52803.
SMRP52803. Positions 28-165.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108266. 6 interactions.
DIPDIP-48296N.
IntActP52803. 2 interactions.
MINTMINT-7241704.
STRING9606.ENSP00000328777.

Polymorphism databases

DMDM1706678.

Proteomic databases

PaxDbP52803.
PeptideAtlasP52803.
PRIDEP52803.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000333274; ENSP00000328777; ENSG00000184349.
GeneID1946.
KEGGhsa:1946.
UCSCuc003kol.3. human.

Organism-specific databases

CTD1946.
GeneCardsGC05M106712.
HGNCHGNC:3225. EFNA5.
HPACAB013282.
MIM601535. gene.
neXtProtNX_P52803.
PharmGKBPA27660.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG241965.
HOGENOMHOG000234373.
HOVERGENHBG051447.
InParanoidP52803.
KOK05462.
OMATERYILY.
OrthoDBEOG70W3FD.
PhylomeDBP52803.

Enzyme and pathway databases

SignaLinkP52803.

Gene expression databases

ArrayExpressP52803.
BgeeP52803.
CleanExHS_EFNA5.
GenevestigatorP52803.

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

EvolutionaryTraceP52803.
GeneWikiEFNA5.
Ephrin-A5.
GenomeRNAi1946.
NextBio7887.
PROP52803.
SOURCESearch...

Entry information

Entry nameEFNA5_HUMAN
AccessionPrimary (citable) accession number: P52803
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 115 of the entry and version 1 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 5

Human chromosome 5: entries, gene names and cross-references to MIM