P52793 (EFNA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Ephrin-A1, secreted form

Gene names

Name:	Efna1
Synonyms:	Epgl1, Epl1, Lerk1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	205 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 recruitement 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-anchor › GPI-anchor By similarity. Ephrin-A1, secreted form: Secreted By similarity.
Post-translational modification	Undergo 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 process	Angiogenesis
Cellular component	Cell membrane Membrane Secreted
Disease	Tumor suppressor
Domain	Signal
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of MAPK activity Inferred from direct assay. Source: MGI angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW aortic valve morphogenesis Inferred from mutant phenotype. Source: BHF-UCL endocardial cushion to mesenchymal transition involved in heart valve formation Inferred from mutant phenotype. Source: BHF-UCL ephrin receptor signaling pathway Inferred from direct assay Ref.6. Source: UniProtKB mitral valve morphogenesis Inferred from mutant phenotype. 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. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: BHF-UCL neuron differentiation Inferred from direct assay. Source: MGI notochord formation Inferred from genetic interaction. Source: MGI regulation of angiogenesis Inferred from direct assay Ref.5. Source: UniProtKB regulation of axonogenesis Inferred from direct assay. Source: MGI regulation of blood vessel endothelial cell migration Inferred from direct assay Ref.5. Source: UniProtKB
Cellular component	anchored to plasma membrane Inferred from direct assay. Source: UniProtKB extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Potential
	Chain	18 – 182	165	Ephrin-A1		PRO_0000008355
	Chain	18 – ?		Ephrin-A1, secreted form		PRO_0000389631
	Propeptide	183 – 205	23	Removed in mature form Potential		PRO_0000008356
Regions
	Domain	18 – 161	144	Ephrin RBD
Amino acid modifications
	Lipidation	182	1	GPI-anchor amidated serine Potential
	Glycosylation	26	1	N-linked (GlcNAc...) Potential
	Disulfide bond	51 ↔ 92		By similarity
	Disulfide bond	80 ↔ 140		By similarity
Experimental info
	Sequence conflict	74	1	H → Y in BAA07344. Ref.1
	Sequence conflict	79	1	A → T in BAA07344. Ref.1
	Sequence conflict	81	1	Q → E in BAA07344. Ref.1
	Sequence conflict	91	1	N → K in BAA07344. Ref.1
	Sequence conflict	94	1	R → Q in BAA07344. Ref.1
	Sequence conflict	112	1	T → S in BAA07344. Ref.1
	Sequence conflict	115	1	I → T in BAA07344. Ref.1
	Sequence conflict	138	1	S → T in BAA07344. Ref.1
	Sequence conflict	154	1	N → S in BAA07344. Ref.1
	Sequence conflict	156	1	Q → H in BAA07344. Ref.1
	Sequence conflict	159	1	V → A in BAA07344. Ref.1
	Sequence conflict	181	1	Y → H in BAA07344. Ref.1
	Sequence conflict	204	1	S → T in BAA07344. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P52793 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 5A8F3A6E2091E868	FASTA	205	23,802
	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

References

	« Hide 'large scale' referencesShow '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: 7675446] [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: 8903354] [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: 15489334] [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: 16782872] [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: 17143272] [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: 18387945] [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.
IPI	IPI00130752.
RefSeq	NP_034237.3. NM_010107.4.
UniGene	Mm.15675.
3D structure databases
ProteinModelPortal	P52793.
SMR	P52793. Positions 18-147.
ModBase	Search...
Protein-protein interaction databases
STRING	P52793.
Proteomic databases
PRIDE	P52793.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000029566; ENSMUSP00000029566; ENSMUSG00000027954.
GeneID	13636.
KEGG	mmu:13636.
UCSC	uc008pyo.2. mouse.
Organism-specific databases
CTD	1942.
MGI	MGI:103236. Efna1.
Phylogenomic databases
eggNOG	roNOG11804.
HOGENOM	HBG717619.
HOVERGEN	HBG051447.
InParanoid	P52793.
OMA	SKDQVRW.
OrthoDB	EOG4D52ZP.
PhylomeDB	P52793.
Gene expression databases
ArrayExpress	P52793.
Bgee	P52793.
CleanEx	MM_EFNA1.
Genevestigator	P52793.
GermOnline	ENSMUSG00000027954. Mus musculus.
Family and domain databases
InterPro	IPR008972. Cupredoxin. IPR001799. Ephrin. IPR019765. Ephrin_CS. [Graphical view]
Gene3D	G3DSA:2.60.40.420. Cupredoxin. 1 hit.
KO	K05462.
PANTHER	PTHR11304. Ephrin. 1 hit.
Pfam	PF00812. Ephrin. 1 hit. [Graphical view]
PRINTS	PR01347. EPHRIN.
ProDom	PD002533. Ephrin. 1 hit. [Graphical view] [Entries sharing at least one domain]
SUPFAM	SSF49503. Cupredoxin. 1 hit.
PROSITE	PS01299. EPHRIN_RBD_1. 1 hit. PS51551. EPHRIN_RBD_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

EFNA1_MOUSE

Accession

Primary (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:	December 14, 2011
This is version 93 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program