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 13-FEB-2019, entry version 145. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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), RT mouse LERK-4/Ephrin-A4 (Epl4), and human LERK-6/Ephrin-A2 (EPLG6): RT conservation 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 RT encoding 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., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA 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 RP EPHA4, 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., RA Rahman-Huq N., Owens R.J., Stuart D.I., Jones E.Y.; RT "Structural plasticity of EPH receptor A4 facilitates cross-class RT ephrin signaling."; RL Structure 17:1386-1397(2009). CC -!- FUNCTION: Cell surface GPI-bound ligand for Eph receptors, a CC family of receptor tyrosine kinases which are crucial for CC migration, repulsion and adhesion during neuronal, vascular and CC epithelial development. Binds promiscuously Eph receptors residing CC on adjacent cells, leading to contact-dependent bidirectional CC signaling into neighboring cells. The signaling pathway downstream CC of the receptor is referred to as forward signaling while the CC signaling pathway downstream of the ephrin ligand is referred to CC as reverse signaling. With the EPHA2 receptor may play a role in CC bone remodeling through regulation of osteoclastogenesis and CC osteoblastogenesis (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Binds to the receptor tyrosine kinases EPHA3, EPHA4 and CC EPHA5. Interacts with EPHA8; activates EPHA8. CC {ECO:0000269|PubMed:19836338}. CC -!- INTERACTION: CC P54764:EPHA4; NbExp=4; IntAct=EBI-8603210, EBI-5773557; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor, CC GPI-anchor {ECO:0000305}. CC -!- SIMILARITY: Belongs to the ephrin family. {ECO:0000255|PROSITE- CC ProRule:PRU00884}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- 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 UniGene; Hs.741510; -. DR PDB; 2WO3; X-ray; 2.35 A; B=33-173. DR PDBsum; 2WO3; -. DR ProteinModelPortal; O43921; -. DR SMR; O43921; -. DR BioGrid; 108263; 4. DR DIP; DIP-48293N; -. DR IntAct; O43921; 3. DR MINT; O43921; -. DR STRING; 9606.ENSP00000215368; -. DR ChEMBL; CHEMBL1795109; -. DR iPTMnet; O43921; -. DR PhosphoSitePlus; O43921; -. DR BioMuta; EFNA2; -. DR jPOST; O43921; -. DR PaxDb; O43921; -. DR PeptideAtlas; O43921; -. DR PRIDE; O43921; -. DR ProteomicsDB; 49238; -. DR DNASU; 1943; -. DR Ensembl; ENST00000215368; ENSP00000215368; ENSG00000099617. DR GeneID; 1943; -. DR KEGG; hsa:1943; -. DR UCSC; uc002lry.3; human. DR CTD; 1943; -. DR DisGeNET; 1943; -. DR EuPathDB; HostDB:ENSG00000099617.3; -. DR GeneCards; EFNA2; -. DR HGNC; HGNC:3222; EFNA2. DR HPA; CAB005178; -. DR HPA; HPA067567; -. DR MIM; 602756; gene. DR neXtProt; NX_O43921; -. DR OpenTargets; ENSG00000099617; -. DR PharmGKB; PA27657; -. DR eggNOG; KOG3858; Eukaryota. DR eggNOG; ENOG4111FMJ; LUCA. DR GeneTree; ENSGT00940000160040; -. DR HOGENOM; HOG000234373; -. DR HOVERGEN; HBG051447; -. DR InParanoid; O43921; -. DR KO; K05462; -. DR OMA; SDRYAVY; -. DR OrthoDB; 1094764at2759; -. DR PhylomeDB; 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 ChiTaRS; EFNA2; human. DR EvolutionaryTrace; O43921; -. DR GeneWiki; EFNA2; -. DR GenomeRNAi; 1943; -. DR PMAP-CutDB; O43921; -. DR PRO; PR:O43921; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; ENSG00000099617; Expressed in 48 organ(s), highest expression level in mucosa of transverse colon. 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 ProDom; PD002533; Ephrin; 1. 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; Complete proteome; Disulfide bond; KW Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Reference proteome; KW Signal. FT SIGNAL 1 24 {ECO:0000255}. FT CHAIN 25 188 Ephrin-A2. FT /FTId=PRO_0000008361. FT PROPEP 189 213 Removed in mature form. {ECO:0000255}. FT /FTId=PRO_0000008362. FT DOMAIN 34 174 Ephrin RBD. {ECO:0000255|PROSITE- FT ProRule:PRU00884}. FT LIPID 188 188 GPI-anchor amidated asparagine. FT {ECO:0000255}. FT CARBOHYD 42 42 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 174 174 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 188 188 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 73 114 {ECO:0000255|PROSITE-ProRule:PRU00884, FT ECO:0000269|PubMed:19836338}. FT DISULFID 102 163 {ECO:0000255|PROSITE-ProRule:PRU00884, FT ECO:0000269|PubMed:19836338}. FT CONFLICT 6 6 R -> A (in Ref. 2; CAA07435). FT {ECO:0000305}. FT CONFLICT 25 26 RA -> PP (in Ref. 2; CAA07435). FT {ECO:0000305}. FT CONFLICT 29 30 AA -> RR (in Ref. 2; CAA07435). FT {ECO:0000305}. FT STRAND 36 40 {ECO:0000244|PDB:2WO3}. FT STRAND 51 53 {ECO:0000244|PDB:2WO3}. FT STRAND 59 63 {ECO:0000244|PDB:2WO3}. FT STRAND 68 72 {ECO:0000244|PDB:2WO3}. FT HELIX 83 85 {ECO:0000244|PDB:2WO3}. FT STRAND 89 94 {ECO:0000244|PDB:2WO3}. FT HELIX 96 101 {ECO:0000244|PDB:2WO3}. FT STRAND 107 114 {ECO:0000244|PDB:2WO3}. FT STRAND 125 129 {ECO:0000244|PDB:2WO3}. FT STRAND 147 153 {ECO:0000244|PDB:2WO3}. FT STRAND 165 170 {ECO:0000244|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 //