ID   EFNA5_RAT               Reviewed;         228 AA.
AC   P97605;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-1998, sequence version 2.
DT   24-JAN-2024, entry version 141.
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC   STRAIN=Sprague-Dawley;
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   STRAIN=Sprague-Dawley;
RA   Li Y.Y., McTiernan C.F., Feldman A.M.;
RT   "rLERK7, rat ligand for Eph-related receptor tyrosine kinase.";
RL   Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
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 (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Binds to the receptor tyrosine kinases EPHA2, EPHA3, EPHB1 and
CC       EPHB2. Interacts with EPHA8; activates EPHA8. Forms a ternary EFNA5-
CC       EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by
CC       ADAM10 which regulates the EFNA5-EPHA3 complex internalization and
CC       function (By similarity). {ECO:0000250}.
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   -!- TISSUE SPECIFICITY: Expressed in brain, heart, placenta and lung.
CC   -!- SIMILARITY: Belongs to the ephrin family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00884}.
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DR   EMBL; U69279; AAC05801.1; -; mRNA.
DR   RefSeq; NP_446355.1; NM_053903.1.
DR   AlphaFoldDB; P97605; -.
DR   SMR; P97605; -.
DR   STRING; 10116.ENSRNOP00000039406; -.
DR   GlyCosmos; P97605; 1 site, No reported glycans.
DR   GlyGen; P97605; 1 site.
DR   PhosphoSitePlus; P97605; -.
DR   PaxDb; 10116-ENSRNOP00000039406; -.
DR   GeneID; 116683; -.
DR   KEGG; rno:116683; -.
DR   UCSC; RGD:620391; rat.
DR   AGR; RGD:620391; -.
DR   CTD; 1946; -.
DR   RGD; 620391; Efna5.
DR   eggNOG; KOG3858; Eukaryota.
DR   InParanoid; P97605; -.
DR   OrthoDB; 2881104at2759; -.
DR   PhylomeDB; P97605; -.
DR   Reactome; R-RNO-2682334; EPH-Ephrin signaling.
DR   Reactome; R-RNO-3928663; EPHA-mediated growth cone collapse.
DR   Reactome; R-RNO-3928665; EPH-ephrin mediated repulsion of cells.
DR   PRO; PR:P97605; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005912; C:adherens junction; ISO:RGD.
DR   GO; GO:0005604; C:basement membrane; ISO:RGD.
DR   GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR   GO; GO:0071944; C:cell periphery; ISO:RGD.
DR   GO; GO:0009897; C:external side of plasma membrane; ISS:UniProtKB.
DR   GO; GO:0098982; C:GABA-ergic synapse; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0045499; F:chemorepellent activity; ISO:RGD.
DR   GO; GO:0046875; F:ephrin receptor binding; IDA:RGD.
DR   GO; GO:0005169; F:neurotrophin TRKB receptor binding; ISO:RGD.
DR   GO; GO:0007411; P:axon guidance; ISO:RGD.
DR   GO; GO:0007413; P:axonal fasciculation; NAS:RGD.
DR   GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; ISO:RGD.
DR   GO; GO:1904322; P:cellular response to forskolin; ISO:RGD.
DR   GO; GO:0048668; P:collateral sprouting; ISO:RGD.
DR   GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; ISO:RGD.
DR   GO; GO:0048672; P:positive regulation of collateral sprouting; ISO:RGD.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR   GO; GO:0051965; P:positive regulation of synapse assembly; ISO:RGD.
DR   GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR   GO; GO:0022604; P:regulation of cell morphogenesis; ISO:RGD.
DR   GO; GO:0022407; P:regulation of cell-cell adhesion; ISS:UniProtKB.
DR   GO; GO:0051893; P:regulation of focal adhesion assembly; ISS:UniProtKB.
DR   GO; GO:0043087; P:regulation of GTPase activity; ISS: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; ISS:UniProtKB.
DR   GO; GO:0031290; P:retinal ganglion cell axon guidance; ISO:RGD.
DR   GO; GO:0099560; P:synaptic membrane adhesion; ISO:RGD.
DR   CDD; cd10425; Ephrin-A_Ectodomain; 1.
DR   Gene3D; 2.60.40.420; Cupredoxins - blue copper proteins; 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; EPHRIN; 1.
DR   PANTHER; PTHR11304:SF33; EPHRIN-A5; 1.
DR   Pfam; PF00812; Ephrin; 1.
DR   PRINTS; PR01347; EPHRIN.
DR   SUPFAM; SSF49503; Cupredoxins; 1.
DR   PROSITE; PS01299; EPHRIN_RBD_1; 1.
DR   PROSITE; PS51551; EPHRIN_RBD_2; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Developmental protein; Differentiation;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; GPI-anchor;
KW   Lipoprotein; Membrane; Neurogenesis; Reference proteome; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..203
FT                   /note="Ephrin-A5"
FT                   /id="PRO_0000008381"
FT   PROPEP          204..228
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000008382"
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:0000255"
FT   DISULFID        62..102
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT   DISULFID        90..151
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
SQ   SEQUENCE   228 AA;  26358 MW;  855985532D580022 CRC64;
     MLHVEMLTLL FLVLWMCVFS QDPGSKVVAD RYAVYWNSSN PRFQRGDYHI DVCINDYLDV
     FCPHYEDSVP EDKTERYVLY MVNFDGYSAC DHTSKGFKRW ECNRPHSPNG PLKFSEKFQL
     FTPFSLGFEF RPGREYFYIS SAIPDNGRRS CLKLKVFVRP TNSCMKTIGV RDRVFDVNDK
     VENSLEPADD TVHESAEPSR GENAAQTPRI PSRLLAILLF LLAMLLTL
//