EFNA1_MOUSE
ID EFNA1_MOUSE Reviewed; 205 AA.
AC P52793; P97331;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Ephrin-A1;
DE AltName: Full=EPH-related receptor tyrosine kinase ligand 1;
DE Short=LERK-1;
DE AltName: Full=Immediate early response protein B61;
DE Contains:
DE RecName: Full=Ephrin-A1, secreted form;
DE Flags: Precursor;
GN Name=Efna1; Synonyms=Epgl1, Epl1, Lerk1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ICR;
RX PubMed=7675446;
RA Takahashi H., Ikeda T.;
RT "Molecular cloning and expression of rat and mouse B61 gene: implications
RT on organogenesis.";
RL Oncogene 11:879-883(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RA Morris J.C., Ciarletta A., Morris G.E., Giannotti J., Caruso A.,
RA Hammett D.J., Finnerty H., Turner K., Wood C.R.;
RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8903354; DOI=10.1006/dbio.1996.0269;
RA Flenniken A.M., Gale N.W., Yancopoulos G.D., Wilkinson D.G.;
RT "Distinct and overlapping expression patterns of ligands for Eph-related
RT receptor tyrosine kinases during mouse embryogenesis.";
RL Dev. Biol. 179:382-401(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION.
RX PubMed=16782872; DOI=10.1128/mcb.02215-05;
RA Hunter S.G., Zhuang G., Brantley-Sieders D.M., Swat W., Cowan C.W.,
RA Chen J.;
RT "Essential role of Vav family guanine nucleotide exchange factors in EphA
RT receptor-mediated angiogenesis.";
RL Mol. Cell. Biol. 26:4830-4842(2006).
RN [6]
RP FUNCTION IN DENDRITIC SPINE MORPHOGENESIS.
RX PubMed=17143272; DOI=10.1038/nn1811;
RA Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O.,
RA Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y.;
RT "Cdk5 regulates EphA4-mediated dendritic spine retraction through an
RT ephexin1-dependent mechanism.";
RL Nat. Neurosci. 10:67-76(2007).
RN [7]
RP FUNCTION.
RX PubMed=18387945; DOI=10.1074/jbc.m709934200;
RA Fang W.B., Brantley-Sieders D.M., Hwang Y., Ham A.-J.L., Chen J.;
RT "Identification and functional analysis of phosphorylated tyrosine residues
RT within EphA2 receptor tyrosine kinase.";
RL J. Biol. Chem. 283:16017-16026(2008).
RN [8]
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=27446912; DOI=10.3389/fcell.2016.00058;
RA Alonso-Martin S., Rochat A., Mademtzoglou D., Morais J., de Reynies A.,
RA Aurade F., Chang T.H., Zammit P.S., Relaix F.;
RT "Gene expression profiling of muscle stem cells identifies novel regulators
RT of postnatal myogenesis.";
RL Front. Cell Dev. Biol. 4:58-58(2016).
CC -!- FUNCTION: Cell surface GPI-bound ligand for Eph receptors, a family of
CC receptor tyrosine kinases which are crucial for migration, repulsion
CC and adhesion during neuronal, vascular and epithelial development.
CC Binds promiscuously Eph receptors residing on adjacent cells, leading
CC to contact-dependent bidirectional signaling into neighboring cells.
CC Plays an important role in angiogenesis and tumor neovascularization.
CC The recruitment of VAV2, VAV3 and PI3-kinase p85 subunit by
CC phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase
CC activation and vascular endothelial cell migration and assembly. Exerts
CC anti-oncogenic effects in tumor cells through activation and down-
CC regulation of EPHA2. Activates EPHA2 by inducing tyrosine
CC phosphorylation which leads to its internalization and degradation.
CC Acts as a negative regulator in the tumorigenesis of gliomas by down-
CC regulating EPHA2 and FAK. Can evoke collapse of embryonic neuronal
CC growth cone and regulates dendritic spine morphogenesis.
CC {ECO:0000269|PubMed:16782872, ECO:0000269|PubMed:17143272,
CC ECO:0000269|PubMed:18387945}.
CC -!- SUBUNIT: Monomer. Homodimer. Forms heterodimers with EPHA2. Binds to
CC the receptor tyrosine kinases EPHA2, EPHA3, EPHA4, EPHA5, EPHA6 and
CC EPHA7. Also binds with low affinity to EPHA1 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC P52793; Q15375: EPHA7; Xeno; NbExp=2; IntAct=EBI-5241529, EBI-1383428;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P20827};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P20827}.
CC -!- SUBCELLULAR LOCATION: [Ephrin-A1, secreted form]: Secreted
CC {ECO:0000250|UniProtKB:P20827}.
CC -!- TISSUE SPECIFICITY: Expressed in myogenic progenitor cells.
CC {ECO:0000269|PubMed:27446912}.
CC -!- DEVELOPMENTAL STAGE: In myogenic progenitor cells, expressed during the
CC acquisition of muscle stem cell properties, from 18.5 dpc to adulthood.
CC {ECO:0000269|PubMed:27446912}.
CC -!- PTM: Undergoes proteolysis by a metalloprotease to give rise to a
CC soluble monomeric form. {ECO:0000250}.
CC -!- PTM: N-Glycosylation is required for binding to EPHA2 receptor and
CC inducing its internalization. {ECO:0000250|UniProtKB:P20827}.
CC -!- SIMILARITY: Belongs to the ephrin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00884}.
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DR EMBL; D38146; BAA07344.1; -; mRNA.
DR EMBL; U26188; AAA67563.1; -; mRNA.
DR EMBL; U90662; AAB50237.1; -; mRNA.
DR EMBL; BC002046; AAH02046.1; -; mRNA.
DR CCDS; CCDS17501.1; -.
DR RefSeq; NP_034237.3; NM_010107.4.
DR AlphaFoldDB; P52793; -.
DR SMR; P52793; -.
DR BioGRID; 199389; 3.
DR IntAct; P52793; 1.
DR STRING; 10090.ENSMUSP00000029566; -.
DR GlyConnect; 2290; 4 N-Linked glycans (1 site).
DR GlyGen; P52793; 1 site, 4 N-linked glycans (1 site).
DR iPTMnet; P52793; -.
DR PhosphoSitePlus; P52793; -.
DR CPTAC; non-CPTAC-3975; -.
DR MaxQB; P52793; -.
DR PaxDb; P52793; -.
DR PRIDE; P52793; -.
DR ProteomicsDB; 277767; -.
DR ABCD; P52793; 11 sequenced antibodies.
DR Antibodypedia; 34167; 371 antibodies from 37 providers.
DR DNASU; 13636; -.
DR Ensembl; ENSMUST00000029566; ENSMUSP00000029566; ENSMUSG00000027954.
DR GeneID; 13636; -.
DR KEGG; mmu:13636; -.
DR UCSC; uc008pyo.2; mouse.
DR CTD; 1942; -.
DR MGI; MGI:103236; Efna1.
DR VEuPathDB; HostDB:ENSMUSG00000027954; -.
DR eggNOG; KOG3858; Eukaryota.
DR GeneTree; ENSGT00940000159919; -.
DR HOGENOM; CLU_081598_2_0_1; -.
DR InParanoid; P52793; -.
DR OMA; GQNSAMR; -.
DR OrthoDB; 1094764at2759; -.
DR PhylomeDB; P52793; -.
DR Reactome; R-MMU-2682334; EPH-Ephrin signaling.
DR Reactome; R-MMU-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR BioGRID-ORCS; 13636; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Efna1; mouse.
DR PRO; PR:P52793; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P52793; protein.
DR Bgee; ENSMUSG00000027954; Expressed in placenta labyrinth and 247 other tissues.
DR ExpressionAtlas; P52793; baseline and differential.
DR Genevisible; P52793; MM.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:ARUK-UCL.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0003180; P:aortic valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; ISO:MGI.
DR GO; GO:0003199; P:endocardial cushion to mesenchymal transition involved in heart valve formation; IMP:BHF-UCL.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0003183; P:mitral valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0061002; P:negative regulation of dendritic spine morphogenesis; IDA:UniProtKB.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IDA:MGI.
DR GO; GO:1903051; P:negative regulation of proteolysis involved in protein catabolic process; ISO:MGI.
DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0030182; P:neuron differentiation; IDA:MGI.
DR GO; GO:0014028; P:notochord formation; IGI:MGI.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; ISO:MGI.
DR GO; GO:1902961; P:positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:0045765; P:regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; IDA:MGI.
DR GO; GO:0043535; P:regulation of blood vessel endothelial cell migration; IDA:UniProtKB.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISO:MGI.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISO:MGI.
DR CDD; cd10425; Ephrin-A_Ectodomain; 1.
DR Gene3D; 2.60.40.420; -; 1.
DR InterPro; IPR008972; Cupredoxin.
DR InterPro; IPR031328; Ephrin.
DR InterPro; IPR034252; Ephrin-A_Ecto.
DR InterPro; IPR019765; Ephrin_CS.
DR InterPro; IPR001799; Ephrin_RBD.
DR PANTHER; PTHR11304; PTHR11304; 1.
DR Pfam; PF00812; Ephrin; 1.
DR PRINTS; PR01347; EPHRIN.
DR SUPFAM; SSF49503; SSF49503; 1.
DR PROSITE; PS01299; EPHRIN_RBD_1; 1.
DR PROSITE; PS51551; EPHRIN_RBD_2; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor;
KW Lipoprotein; Membrane; Reference proteome; Secreted; Signal;
KW Tumor suppressor.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..182
FT /note="Ephrin-A1"
FT /id="PRO_0000008355"
FT CHAIN 18..?
FT /note="Ephrin-A1, secreted form"
FT /id="PRO_0000389631"
FT PROPEP 183..205
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000008356"
FT DOMAIN 18..161
FT /note="Ephrin RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT LIPID 182
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 51..92
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT DISULFID 80..140
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT CONFLICT 74
FT /note="H -> Y (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 79
FT /note="A -> T (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 81
FT /note="Q -> E (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 91
FT /note="N -> K (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 94
FT /note="R -> Q (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="T -> S (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="I -> T (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="S -> T (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="N -> S (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="Q -> H (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 159
FT /note="V -> A (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="Y -> H (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="S -> T (in Ref. 1; BAA07344)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 205 AA; 23802 MW; 5A8F3A6E2091E868 CRC64;
MEFLWAPLLG LCCSLAAADR HIVFWNSSNP KFREEDYTVH VQLNDYLDII CPHYEDDSVA
DAAMERYTLY MVEHQEYVAC QPQSKDQVRW NCNRPSAKHG PEKLSEKFQR FTPFILGKEF
KEGHSYYYIS KPIYHQESQC LKLKVTVNGK ITHNPQAHVN PQEKRLQADD PEVQVLHSIG
YSAAPRLFPL VWAVLLLPLL LLQSQ
