EFNA5_MOUSE
ID EFNA5_MOUSE Reviewed; 228 AA.
AC O08543; O08544;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Ephrin-A5;
DE AltName: Full=AL-1;
DE AltName: Full=EPH-related receptor tyrosine kinase ligand 7;
DE Short=LERK-7;
DE Flags: Precursor;
GN Name=Efna5; Synonyms=Epl7, Eplg7, Lerk7;
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] (ISOFORMS LONG AND SHORT).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC STRAIN=FVB/N; 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 [3]
RP FUNCTION IN EPHA8 ACTIVATION, AND INTERACTION WITH EPHA8.
RX PubMed=9053851; DOI=10.1038/sj.onc.1200857;
RA Park S., Sanchez M.P.;
RT "The Eek receptor, a member of the Eph family of tyrosine protein kinases,
RT can be activated by three different Eph family ligands.";
RL Oncogene 14:533-542(1997).
RN [4]
RP FUNCTION IN CELL ADHESION AND REPULSION, AND EPHA7 RECEPTOR-BINDING.
RX PubMed=11089974; DOI=10.1038/35041577;
RA Holmberg J., Clarke D.L., Frisen J.;
RT "Regulation of repulsion versus adhesion by different splice forms of an
RT Eph receptor.";
RL Nature 408:203-206(2000).
RN [5]
RP FUNCTION IN INSULIN SECRETION.
RX PubMed=17448994; DOI=10.1016/j.cell.2007.02.044;
RA Konstantinova I., Nikolova G., Ohara-Imaizumi M., Meda P., Kucera T.,
RA Zarbalis K., Wurst W., Nagamatsu S., Lammert E.;
RT "EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion
RT from pancreatic islets.";
RL Cell 129:359-370(2007).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN LENS FIBER CELLS MORPHOGENESIS.
RX PubMed=18948590; DOI=10.1073/pnas.0808987105;
RA Cooper M.A., Son A.I., Komlos D., Sun Y., Kleiman N.J., Zhou R.;
RT "Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to
RT cataract.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:16620-16625(2008).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-162.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
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).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 28-165 ALONE AND IN COMPLEX WITH
RP EPHB2, GLYCOSYLATION AT ASN-37, AND DISULFIDE BONDS.
RX PubMed=15107857; DOI=10.1038/nn1237;
RA Himanen J.P., Chumley M.J., Lackmann M., Li C., Barton W.A., Jeffrey P.D.,
RA Vearing C., Geleick D., Feldheim D.A., Boyd A.W., Henkemeyer M.,
RA Nikolov D.B.;
RT "Repelling class discrimination: ephrin-A5 binds to and activates EphB2
RT receptor signaling.";
RL Nat. Neurosci. 7:501-509(2004).
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 The signaling pathway downstream of the receptor is referred to as
CC forward signaling while the signaling pathway downstream of the ephrin
CC ligand is referred to as reverse signaling. Induces compartmentalized
CC signaling within a caveolae-like membrane microdomain when bound to the
CC extracellular domain of its cognate receptor. This signaling event
CC requires the activity of the Fyn tyrosine kinase. Activates the EPHA3
CC receptor to regulate cell-cell adhesion and cytoskeletal organization.
CC With the receptor EPHA2 may regulate lens fiber cells shape and
CC interactions and be important for lens transparency maintenance. May
CC function actively to stimulate axon fasciculation. The interaction of
CC EFNA5 with EPHA5 also mediates communication between pancreatic islet
CC cells to regulate glucose-stimulated insulin secretion.
CC Cognate/functional ligand for EPHA7, their interaction regulates brain
CC development modulating cell-cell adhesion and repulsion.
CC {ECO:0000269|PubMed:11089974, ECO:0000269|PubMed:17448994,
CC ECO:0000269|PubMed:18948590, ECO:0000269|PubMed:9053851}.
CC -!- SUBUNIT: Binds to the receptor tyrosine kinases EPHA2, EPHA3 and EPHB1.
CC Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5
CC extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3
CC complex internalization and function (By similarity). Binds to EPHB2.
CC Interacts with EPHA8; activates EPHA8. {ECO:0000250,
CC ECO:0000269|PubMed:15107857, ECO:0000269|PubMed:9053851}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-
CC anchor {ECO:0000250}. Membrane, caveola {ECO:0000250}; Lipid-anchor,
CC GPI-anchor {ECO:0000250}. Note=Compartmentalized in discrete caveolae-
CC like membrane microdomains. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=O08543-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=O08543-2; Sequence=VSP_001449;
CC -!- TISSUE SPECIFICITY: Expressed in myogenic progenitor cells.
CC {ECO:0000269|PubMed:27446912}.
CC -!- DEVELOPMENTAL STAGE: In myogenic progenitor cells, highly expressed at
CC 11.5 dpc and ceases its expression at the late fetal stage (17.5 dpc).
CC {ECO:0000269|PubMed:27446912}.
CC -!- DISRUPTION PHENOTYPE: Mice display cataract an opacification of the
CC lens. {ECO:0000269|PubMed:18948590}.
CC -!- SIMILARITY: Belongs to the ephrin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00884}.
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DR EMBL; U90664; AAB50239.1; -; mRNA.
DR EMBL; U90665; AAB50240.1; -; mRNA.
DR EMBL; BC040218; AAH40218.1; -; mRNA.
DR CCDS; CCDS28934.1; -. [O08543-2]
DR CCDS; CCDS28935.1; -. [O08543-1]
DR RefSeq; NP_034239.1; NM_010109.3. [O08543-2]
DR RefSeq; NP_997537.1; NM_207654.2. [O08543-1]
DR PDB; 1SHW; X-ray; 2.20 A; A=28-164.
DR PDB; 1SHX; X-ray; 2.10 A; A/B=28-164.
DR PDBsum; 1SHW; -.
DR PDBsum; 1SHX; -.
DR AlphaFoldDB; O08543; -.
DR SMR; O08543; -.
DR BioGRID; 199393; 2.
DR IntAct; O08543; 2.
DR STRING; 10090.ENSMUSP00000076115; -.
DR GlyConnect; 2293; 1 N-Linked glycan (1 site).
DR GlyGen; O08543; 2 sites, 1 N-linked glycan (1 site).
DR iPTMnet; O08543; -.
DR PhosphoSitePlus; O08543; -.
DR PaxDb; O08543; -.
DR PRIDE; O08543; -.
DR ProteomicsDB; 277555; -. [O08543-1]
DR ProteomicsDB; 277556; -. [O08543-2]
DR Antibodypedia; 25277; 275 antibodies from 34 providers.
DR DNASU; 13640; -.
DR Ensembl; ENSMUST00000076840; ENSMUSP00000076115; ENSMUSG00000048915. [O08543-1]
DR Ensembl; ENSMUST00000078839; ENSMUSP00000077883; ENSMUSG00000048915. [O08543-2]
DR GeneID; 13640; -.
DR KEGG; mmu:13640; -.
DR UCSC; uc008dfg.2; mouse. [O08543-1]
DR UCSC; uc008dfh.2; mouse. [O08543-2]
DR CTD; 1946; -.
DR MGI; MGI:107444; Efna5.
DR VEuPathDB; HostDB:ENSMUSG00000048915; -.
DR eggNOG; KOG3858; Eukaryota.
DR GeneTree; ENSGT00940000157299; -.
DR HOGENOM; CLU_081598_0_0_1; -.
DR InParanoid; O08543; -.
DR OMA; PRDETSH; -.
DR OrthoDB; 1094764at2759; -.
DR PhylomeDB; O08543; -.
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; 13640; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Efna5; mouse.
DR EvolutionaryTrace; O08543; -.
DR PRO; PR:O08543; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; O08543; protein.
DR Bgee; ENSMUSG00000048915; Expressed in superior cervical ganglion and 242 other tissues.
DR Genevisible; O08543; MM.
DR GO; GO:0005912; C:adherens junction; IDA:MGI.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005604; C:basement membrane; IDA:MGI.
DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR GO; GO:0071944; C:cell periphery; IDA:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045499; F:chemorepellent activity; IDA:MGI.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0005169; F:neurotrophin TRKB receptor binding; IPI:BHF-UCL.
DR GO; GO:0007411; P:axon guidance; IDA:MGI.
DR GO; GO:0007420; P:brain development; ISO:MGI.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IDA:MGI.
DR GO; GO:1904322; P:cellular response to forskolin; IDA:MGI.
DR GO; GO:0048668; P:collateral sprouting; IDA:BHF-UCL.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; ISO:MGI.
DR GO; GO:0048672; P:positive regulation of collateral sprouting; IMP:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IDA:BHF-UCL.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0022604; P:regulation of cell morphogenesis; ISO:MGI.
DR GO; GO:0022407; P:regulation of cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; IDA:MGI.
DR GO; GO:0099560; P:synaptic membrane adhesion; IDA:SynGO.
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 3D-structure; Alternative splicing; Cell membrane; Developmental protein;
KW Differentiation; Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein;
KW Membrane; Neurogenesis; Reference proteome; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..203
FT /note="Ephrin-A5"
FT /id="PRO_0000008379"
FT PROPEP 204..228
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000008380"
FT DOMAIN 29..162
FT /note="Ephrin RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT REGION 186..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 203
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15107857"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine; atypical"
FT /evidence="ECO:0000269|PubMed:19656770"
FT DISULFID 62..102
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884,
FT ECO:0000269|PubMed:15107857"
FT DISULFID 90..151
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884,
FT ECO:0000269|PubMed:15107857"
FT VAR_SEQ 163..189
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:8903354"
FT /id="VSP_001449"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:1SHX"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:1SHX"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:1SHX"
FT STRAND 57..61
FT /evidence="ECO:0007829|PDB:1SHX"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:1SHW"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:1SHW"
FT STRAND 77..82
FT /evidence="ECO:0007829|PDB:1SHX"
FT HELIX 84..88
FT /evidence="ECO:0007829|PDB:1SHX"
FT STRAND 92..102
FT /evidence="ECO:0007829|PDB:1SHX"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:1SHW"
FT STRAND 113..117
FT /evidence="ECO:0007829|PDB:1SHX"
FT STRAND 134..144
FT /evidence="ECO:0007829|PDB:1SHX"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:1SHW"
FT STRAND 153..158
FT /evidence="ECO:0007829|PDB:1SHX"
FT TURN 161..164
FT /evidence="ECO:0007829|PDB:1SHX"
SQ SEQUENCE 228 AA; 26339 MW; 85439F5337420022 CRC64;
MLHVEMLTLL FLVLWMCVFS QDPGSKVVAD RYAVYWNSSN PRFQRGDYHI DVCINDYLDV
FCPHYEDSVP EDKTERYVLY MVNFDGYSAC DHTSKGFKRW ECNRPHSPNG PLKFSEKFQL
FTPFSLGFEF RPGREYFYIS SAIPDNGRRS CLKLKVFVRP TNSCMKTIGV HDRVFDVNDK
VENSLEPADD TVHESAEPSR GENAAQTPRI PSRLLAILLF LLAMLLTL
