EFNA2_HUMAN
ID EFNA2_HUMAN Reviewed; 213 AA.
AC O43921; O76020;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Ephrin-A2;
DE AltName: Full=EPH-related receptor tyrosine kinase ligand 6;
DE Short=LERK-6;
DE AltName: Full=HEK7 ligand;
DE Short=HEK7-L;
DE Flags: Precursor;
GN Name=EFNA2; Synonyms=EPLG6, LERK6;
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 [GENOMIC DNA].
RX PubMed=9465306; DOI=10.1006/geno.1997.5088;
RA Cerretti D.P., Nelson N.;
RT "Characterization of the genes for mouse LERK-3/Ephrin-A3 (Epl3), mouse
RT LERK-4/Ephrin-A4 (Epl4), and human LERK-6/Ephrin-A2 (EPLG6): conservation
RT of intron/exon structure.";
RL Genomics 47:131-135(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9826538; DOI=10.1006/bbrc.1998.9618;
RA Aasheim H.-C., Pedeutour F., Grosgeorge J., Logtenberg T.;
RT "Cloning, chromosomal mapping, and tissue expression of the gene encoding
RT the human Eph-family kinase ligand ephrin-A2.";
RL Biochem. Biophys. Res. Commun. 252:378-382(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 33-177 IN COMPLEX WITH EPHA4,
RP DISULFIDE BONDS, AND SUBUNIT.
RX PubMed=19836338; DOI=10.1016/j.str.2009.07.018;
RA Bowden T.A., Aricescu A.R., Nettleship J.E., Siebold C., Rahman-Huq N.,
RA Owens R.J., Stuart D.I., Jones E.Y.;
RT "Structural plasticity of EPH receptor A4 facilitates cross-class ephrin
RT signaling.";
RL Structure 17:1386-1397(2009).
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. With the EPHA2 receptor may
CC play a role in bone remodeling through regulation of osteoclastogenesis
CC and osteoblastogenesis (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binds to the receptor tyrosine kinases EPHA3, EPHA4 and EPHA5.
CC Interacts with EPHA8; activates EPHA8. {ECO:0000269|PubMed:19836338}.
CC -!- INTERACTION:
CC O43921; P54764: EPHA4; NbExp=4; IntAct=EBI-8603210, EBI-5773557;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor, GPI-
CC anchor {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ephrin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00884}.
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DR EMBL; U92896; AAC39577.1; -; Genomic_DNA.
DR EMBL; U92893; AAC39577.1; JOINED; Genomic_DNA.
DR EMBL; U92894; AAC39577.1; JOINED; Genomic_DNA.
DR EMBL; AJ007292; CAA07435.1; -; mRNA.
DR EMBL; AC004258; AAC04896.1; -; Genomic_DNA.
DR CCDS; CCDS12061.1; -.
DR PIR; JE0322; JE0322.
DR RefSeq; NP_001396.2; NM_001405.3.
DR PDB; 2WO3; X-ray; 2.35 A; B=33-173.
DR PDBsum; 2WO3; -.
DR AlphaFoldDB; O43921; -.
DR SMR; O43921; -.
DR BioGRID; 108263; 92.
DR DIP; DIP-48293N; -.
DR IntAct; O43921; 3.
DR MINT; O43921; -.
DR STRING; 9606.ENSP00000215368; -.
DR ChEMBL; CHEMBL1795109; -.
DR GlyGen; O43921; 3 sites.
DR iPTMnet; O43921; -.
DR PhosphoSitePlus; O43921; -.
DR BioMuta; EFNA2; -.
DR jPOST; O43921; -.
DR MassIVE; O43921; -.
DR PaxDb; O43921; -.
DR PeptideAtlas; O43921; -.
DR PRIDE; O43921; -.
DR ProteomicsDB; 49238; -.
DR Antibodypedia; 3919; 414 antibodies from 31 providers.
DR DNASU; 1943; -.
DR Ensembl; ENST00000215368.4; ENSP00000215368.1; ENSG00000099617.4.
DR GeneID; 1943; -.
DR KEGG; hsa:1943; -.
DR MANE-Select; ENST00000215368.4; ENSP00000215368.1; NM_001405.4; NP_001396.2.
DR UCSC; uc002lry.3; human.
DR CTD; 1943; -.
DR DisGeNET; 1943; -.
DR GeneCards; EFNA2; -.
DR HGNC; HGNC:3222; EFNA2.
DR HPA; ENSG00000099617; Tissue enhanced (intestine, liver).
DR MIM; 602756; gene.
DR neXtProt; NX_O43921; -.
DR OpenTargets; ENSG00000099617; -.
DR PharmGKB; PA27657; -.
DR VEuPathDB; HostDB:ENSG00000099617; -.
DR eggNOG; KOG3858; Eukaryota.
DR GeneTree; ENSGT00940000160040; -.
DR HOGENOM; CLU_081598_3_1_1; -.
DR InParanoid; O43921; -.
DR OMA; NPRFFRG; -.
DR OrthoDB; 1094764at2759; -.
DR PhylomeDB; O43921; -.
DR PathwayCommons; O43921; -.
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; O43921; -.
DR SIGNOR; O43921; -.
DR BioGRID-ORCS; 1943; 14 hits in 1062 CRISPR screens.
DR ChiTaRS; EFNA2; human.
DR EvolutionaryTrace; O43921; -.
DR GeneWiki; EFNA2; -.
DR GenomeRNAi; 1943; -.
DR Pharos; O43921; Tbio.
DR PRO; PR:O43921; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O43921; protein.
DR Bgee; ENSG00000099617; Expressed in ileal mucosa and 70 other tissues.
DR Genevisible; O43921; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0046875; F:ephrin receptor binding; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0046849; P:bone remodeling; ISS:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0021772; P:olfactory bulb development; IEA:Ensembl.
DR GO; GO:0030316; P:osteoclast differentiation; ISS:UniProtKB.
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; Disulfide bond; Glycoprotein; GPI-anchor;
KW Lipoprotein; Membrane; Reference proteome; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..188
FT /note="Ephrin-A2"
FT /id="PRO_0000008361"
FT PROPEP 189..213
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000008362"
FT DOMAIN 34..174
FT /note="Ephrin RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT LIPID 188
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 73..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884,
FT ECO:0000269|PubMed:19836338"
FT DISULFID 102..163
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884,
FT ECO:0000269|PubMed:19836338"
FT CONFLICT 6
FT /note="R -> A (in Ref. 2; CAA07435)"
FT /evidence="ECO:0000305"
FT CONFLICT 25..26
FT /note="RA -> PP (in Ref. 2; CAA07435)"
FT /evidence="ECO:0000305"
FT CONFLICT 29..30
FT /note="AA -> RR (in Ref. 2; CAA07435)"
FT /evidence="ECO:0000305"
FT STRAND 36..40
FT /evidence="ECO:0007829|PDB:2WO3"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:2WO3"
FT STRAND 59..63
FT /evidence="ECO:0007829|PDB:2WO3"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:2WO3"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:2WO3"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:2WO3"
FT HELIX 96..101
FT /evidence="ECO:0007829|PDB:2WO3"
FT STRAND 107..114
FT /evidence="ECO:0007829|PDB:2WO3"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:2WO3"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:2WO3"
FT STRAND 165..170
FT /evidence="ECO:0007829|PDB:2WO3"
SQ SEQUENCE 213 AA; 23878 MW; 33C9FB1A8168B2D0 CRC64;
MAPAQRPLLP LLLLLLPLPP PPFARAEDAA RANSDRYAVY WNRSNPRFHA GAGDDGGGYT
VEVSINDYLD IYCPHYGAPL PPAERMEHYV LYMVNGEGHA SCDHRQRGFK RWECNRPAAP
GGPLKFSEKF QLFTPFSLGF EFRPGHEYYY ISATPPNAVD RPCLRLKVYV RPTNETLYEA
PEPIFTSNNS CSSPGGCRLF LSTIPVLWTL LGS
