EFNA5_HUMAN
ID EFNA5_HUMAN Reviewed; 228 AA.
AC P52803;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 174.
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=EPLG7, LERK7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7748564; DOI=10.1016/0896-6273(95)90335-6;
RA Winslow J.W., Moran P., Valverde J., Shih A., Yuan J.Q., Wong S.C.,
RA Tsai S.P., Goddard A., Henzel W.J., Hefti F., Beck K.D., Caras I.W.;
RT "Cloning of AL-1, a ligand for an Eph-related tyrosine kinase receptor
RT involved in axon bundle formation.";
RL Neuron 14:973-981(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9245480; DOI=10.1006/cyto.1997.0199;
RA Kozlosky C.J., Vanden Bos T., Park L.S., Cerretti D.P., Carpenter M.K.;
RT "LERK-7: a ligand of the Eph-related kinases is developmentally regulated
RT in the brain.";
RL Cytokine 9:540-549(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP FUNCTION.
RX PubMed=10601038; DOI=10.1101/gad.13.23.3125;
RA Davy A., Gale N.W., Murray E.W., Klinghoffer R.A., Soriano P.,
RA Feuerstein C., Robbins S.M.;
RT "Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn
RT tyrosine kinase to regulate cellular adhesion.";
RL Genes Dev. 13:3125-3135(1999).
RN [5]
RP FUNCTION IN CELL-CELL ADHESION, EPHA3-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=11870224; DOI=10.1242/jcs.115.5.1059;
RA Lawrenson I.D., Wimmer-Kleikamp S.H., Lock P., Schoenwaelder S.M., Down M.,
RA Boyd A.W., Alewood P.F., Lackmann M.;
RT "Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing
RT 293T and melanoma cells by CrkII and Rho-mediated signalling.";
RL J. Cell Sci. 115:1059-1072(2002).
RN [6]
RP IDENTIFICATION IN A COMPLEX WITH ADAM10 AND EPHA3.
RX PubMed=16239146; DOI=10.1016/j.cell.2005.08.014;
RA Janes P.W., Saha N., Barton W.A., Kolev M.V., Wimmer-Kleikamp S.H.,
RA Nievergall E., Blobel C.P., Himanen J.P., Lackmann M., Nikolov D.B.;
RT "Adam meets Eph: an ADAM substrate recognition module acts as a molecular
RT switch for ephrin cleavage in trans.";
RL Cell 123:291-304(2005).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 27-189, GLYCOSYLATION AT ASN-37,
RP AND DISULFIDE BONDS.
RX PubMed=17400922; DOI=10.1110/ps.062665807;
RA Nikolov D.B., Li C., Lackmann M., Jeffrey P., Himanen J.P.;
RT "Crystal structure of the human ephrin-A5 ectodomain.";
RL Protein Sci. 16:996-1000(2007).
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:10601038, ECO:0000269|PubMed:11870224}.
CC -!- SUBUNIT: Binds to EPHB2. Interacts with EPHA8; activates EPHA8 (By
CC similarity). Binds to the receptor tyrosine kinases EPHA2, EPHA3 and
CC EPHB1. 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. {ECO:0000250,
CC ECO:0000269|PubMed:16239146}.
CC -!- INTERACTION:
CC P52803; O00590: ACKR2; NbExp=3; IntAct=EBI-1753674, EBI-13379418;
CC P52803; P41181: AQP2; NbExp=3; IntAct=EBI-1753674, EBI-12701138;
CC P52803; Q13520: AQP6; NbExp=3; IntAct=EBI-1753674, EBI-13059134;
CC P52803; Q8NFU1: BEST2; NbExp=3; IntAct=EBI-1753674, EBI-19947314;
CC P52803; P19397: CD53; NbExp=3; IntAct=EBI-1753674, EBI-6657396;
CC P52803; O00501: CLDN5; NbExp=3; IntAct=EBI-1753674, EBI-18400628;
CC P52803; P49447: CYB561; NbExp=3; IntAct=EBI-1753674, EBI-8646596;
CC P52803; P29317: EPHA2; NbExp=6; IntAct=EBI-1753674, EBI-702104;
CC P52803; P54764: EPHA4; NbExp=2; IntAct=EBI-1753674, EBI-5773557;
CC P52803; O14843: FFAR3; NbExp=3; IntAct=EBI-1753674, EBI-17762181;
CC P52803; P08034: GJB1; NbExp=3; IntAct=EBI-1753674, EBI-17565645;
CC P52803; Q8TDV0: GPR151; NbExp=3; IntAct=EBI-1753674, EBI-11955647;
CC P52803; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-1753674, EBI-13345167;
CC P52803; Q8N6U8: GPR161; NbExp=3; IntAct=EBI-1753674, EBI-6255622;
CC P52803; O15529: GPR42; NbExp=3; IntAct=EBI-1753674, EBI-18076404;
CC P52803; Q9BSE4: HERPUD2; NbExp=3; IntAct=EBI-1753674, EBI-2868124;
CC P52803; P31937: HIBADH; NbExp=3; IntAct=EBI-1753674, EBI-11427100;
CC P52803; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-1753674, EBI-749265;
CC P52803; Q96HJ5: MS4A3; NbExp=3; IntAct=EBI-1753674, EBI-12806656;
CC P52803; Q9UBD6: RHCG; NbExp=3; IntAct=EBI-1753674, EBI-15853497;
CC P52803; O95470: SGPL1; NbExp=3; IntAct=EBI-1753674, EBI-1046170;
CC P52803; Q12908: SLC10A2; NbExp=3; IntAct=EBI-1753674, EBI-18114847;
CC P52803; Q9UKG4: SLC13A4; NbExp=3; IntAct=EBI-1753674, EBI-12808018;
CC P52803; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-1753674, EBI-17295964;
CC P52803; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-1753674, EBI-17280858;
CC P52803; Q96CE8: TM4SF18; NbExp=3; IntAct=EBI-1753674, EBI-13351685;
CC P52803; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-1753674, EBI-10982110;
CC P52803; P34981: TRHR; NbExp=3; IntAct=EBI-1753674, EBI-18055230;
CC P52803; Q5TGU0: TSPO2; NbExp=3; IntAct=EBI-1753674, EBI-12195249;
CC P52803; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-1753674, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11870224};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:11870224}. Membrane,
CC caveola {ECO:0000269|PubMed:11870224}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:11870224}. Note=Compartmentalized in discrete
CC caveolae-like membrane microdomains.
CC -!- SIMILARITY: Belongs to the ephrin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00884}.
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DR EMBL; U26403; AAB60377.1; -; mRNA.
DR EMBL; BC075054; AAH75054.1; -; mRNA.
DR EMBL; BC075055; AAH75055.1; -; mRNA.
DR CCDS; CCDS4097.1; -.
DR PIR; I58170; I58170.
DR RefSeq; NP_001953.1; NM_001962.2.
DR PDB; 2X11; X-ray; 4.83 A; B=27-166.
DR PDB; 3MX0; X-ray; 3.51 A; B/D=28-165.
DR PDB; 4BK5; X-ray; 4.00 A; C=27-166.
DR PDB; 4BKA; X-ray; 5.30 A; C=27-166.
DR PDB; 4L0P; X-ray; 2.26 A; B=27-166.
DR PDB; 4M4R; X-ray; 3.13 A; B/D/F/H=27-165.
DR PDBsum; 2X11; -.
DR PDBsum; 3MX0; -.
DR PDBsum; 4BK5; -.
DR PDBsum; 4BKA; -.
DR PDBsum; 4L0P; -.
DR PDBsum; 4M4R; -.
DR AlphaFoldDB; P52803; -.
DR SMR; P52803; -.
DR BioGRID; 108266; 66.
DR DIP; DIP-48296N; -.
DR IntAct; P52803; 38.
DR STRING; 9606.ENSP00000328777; -.
DR GlyConnect; 1212; 2 N-Linked glycans (1 site).
DR GlyGen; P52803; 3 sites, 3 N-linked glycans (1 site).
DR iPTMnet; P52803; -.
DR PhosphoSitePlus; P52803; -.
DR BioMuta; EFNA5; -.
DR DMDM; 1706678; -.
DR EPD; P52803; -.
DR jPOST; P52803; -.
DR MassIVE; P52803; -.
DR MaxQB; P52803; -.
DR PaxDb; P52803; -.
DR PeptideAtlas; P52803; -.
DR PRIDE; P52803; -.
DR ProteomicsDB; 56539; -.
DR Antibodypedia; 25277; 275 antibodies from 34 providers.
DR DNASU; 1946; -.
DR Ensembl; ENST00000333274.11; ENSP00000328777.6; ENSG00000184349.14.
DR GeneID; 1946; -.
DR KEGG; hsa:1946; -.
DR MANE-Select; ENST00000333274.11; ENSP00000328777.6; NM_001962.3; NP_001953.1.
DR UCSC; uc003kol.3; human.
DR CTD; 1946; -.
DR DisGeNET; 1946; -.
DR GeneCards; EFNA5; -.
DR HGNC; HGNC:3225; EFNA5.
DR HPA; ENSG00000184349; Low tissue specificity.
DR MIM; 601535; gene.
DR neXtProt; NX_P52803; -.
DR OpenTargets; ENSG00000184349; -.
DR PharmGKB; PA27660; -.
DR VEuPathDB; HostDB:ENSG00000184349; -.
DR eggNOG; KOG3858; Eukaryota.
DR GeneTree; ENSGT00940000157299; -.
DR InParanoid; P52803; -.
DR OMA; PRDETSH; -.
DR OrthoDB; 1094764at2759; -.
DR PhylomeDB; P52803; -.
DR PathwayCommons; P52803; -.
DR Reactome; R-HSA-2682334; EPH-Ephrin signaling.
DR Reactome; R-HSA-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells.
DR SignaLink; P52803; -.
DR SIGNOR; P52803; -.
DR BioGRID-ORCS; 1946; 16 hits in 1072 CRISPR screens.
DR ChiTaRS; EFNA5; human.
DR EvolutionaryTrace; P52803; -.
DR GeneWiki; EFNA5; -.
DR GeneWiki; Ephrin-A5; -.
DR GenomeRNAi; 1946; -.
DR Pharos; P52803; Tbio.
DR PRO; PR:P52803; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P52803; protein.
DR Bgee; ENSG00000184349; Expressed in hair follicle and 186 other tissues.
DR ExpressionAtlas; P52803; baseline and differential.
DR Genevisible; P52803; HS.
DR GO; GO:0005912; C:adherens junction; IEA:Ensembl.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005604; C:basement membrane; IEA:Ensembl.
DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0045499; F:chemorepellent activity; IEA:Ensembl.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; NAS:BHF-UCL.
DR GO; GO:0005169; F:neurotrophin TRKB receptor binding; NAS:BHF-UCL.
DR GO; GO:0005170; F:neurotrophin TRKC receptor binding; NAS:BHF-UCL.
DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; NAS:BHF-UCL.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEA:Ensembl.
DR GO; GO:1904322; P:cellular response to forskolin; IEA:Ensembl.
DR GO; GO:0048668; P:collateral sprouting; IEA:Ensembl.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; IDA:MGI.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0048672; P:positive regulation of collateral sprouting; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; NAS:BHF-UCL.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IEA:Ensembl.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0022604; P:regulation of cell morphogenesis; IDA:MGI.
DR GO; GO:0022407; P:regulation of cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; IDA: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; ISS:UniProtKB.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; IEA:Ensembl.
DR GO; GO:0099560; P:synaptic membrane adhesion; IEA:Ensembl.
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; Cell membrane; Developmental protein; Differentiation;
KW Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW Neurogenesis; Reference proteome; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..203
FT /note="Ephrin-A5"
FT /id="PRO_0000008377"
FT PROPEP 204..228
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000008378"
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:17400922"
FT DISULFID 62..102
FT /evidence="ECO:0000269|PubMed:17400922"
FT DISULFID 90..151
FT /evidence="ECO:0000269|PubMed:17400922"
FT VARIANT 55
FT /note="N -> K (in dbSNP:rs469062)"
FT /id="VAR_012035"
FT STRAND 31..35
FT /evidence="ECO:0007829|PDB:4L0P"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:4L0P"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:4L0P"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:4L0P"
FT STRAND 57..61
FT /evidence="ECO:0007829|PDB:4L0P"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:4L0P"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:4L0P"
FT HELIX 84..89
FT /evidence="ECO:0007829|PDB:4L0P"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:4L0P"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:4L0P"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:4M4R"
FT STRAND 113..117
FT /evidence="ECO:0007829|PDB:4L0P"
FT STRAND 135..144
FT /evidence="ECO:0007829|PDB:4L0P"
FT STRAND 153..158
FT /evidence="ECO:0007829|PDB:4L0P"
FT HELIX 161..164
FT /evidence="ECO:0007829|PDB:4L0P"
SQ SEQUENCE 228 AA; 26297 MW; 6893B1CCACFF3F57 CRC64;
MLHVEMLTLV FLVLWMCVFS QDPGSKAVAD RYAVYWNSSN PRFQRGDYHI DVCINDYLDV
FCPHYEDSVP EDKTERYVLY MVNFDGYSAC DHTSKGFKRW ECNRPHSPNG PLKFSEKFQL
FTPFSLGFEF RPGREYFYIS SAIPDNGRRS CLKLKVFVRP TNSCMKTIGV HDRVFDVNDK
VENSLEPADD TVHESAEPSR GENAAQTPRI PSRLLAILLF LLAMLLTL
