EFNA3_HUMAN
ID EFNA3_HUMAN Reviewed; 238 AA.
AC P52797; B7ZAD3; D3DV85; Q0VGC9; Q5SR70;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Ephrin-A3;
DE AltName: Full=EFL-2;
DE AltName: Full=EHK1 ligand;
DE Short=EHK1-L;
DE AltName: Full=EPH-related receptor tyrosine kinase ligand 3;
DE Short=LERK-3;
DE Flags: Precursor;
GN Name=EFNA3; Synonyms=EFL2, EPLG3, LERK3;
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] (ISOFORM 1).
RX PubMed=7838529;
RA Kozlosky C.J., Maraskovsky E., McGrew J.T., Vanden Bos T., Teepe M.,
RA Lyman S.D., Srinivasan S., Fletcher F.A., Gayle R.B. III, Cerretti D.P.,
RA Beckmann M.P.;
RT "Ligands for the receptor tyrosine kinases hek and elk: isolation of cDNAs
RT encoding a family of proteins.";
RL Oncogene 10:299-306(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7973638; DOI=10.1126/science.7973638;
RA Davis S., Gale N.W., Aldrich T.H., Maisonpierre P.C., Lhotak V., Pawson T.,
RA Goldfarb M., Yancopoulos G.D.;
RT "Ligands for EPH-related receptor tyrosine kinases that require membrane
RT attachment or clustering for activity.";
RL Science 266:816-819(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Duodenum;
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).
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 (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with EPHA8; activates EPHA8.
CC -!- INTERACTION:
CC P52797; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-722730, EBI-11959885;
CC P52797; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-722730, EBI-11973993;
CC P52797; P50222: MEOX2; NbExp=3; IntAct=EBI-722730, EBI-748397;
CC P52797; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-722730, EBI-945833;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P52797-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P52797-2; Sequence=VSP_055483;
CC -!- TISSUE SPECIFICITY: Expressed in brain, skeletal muscle, spleen,
CC thymus, prostate, testis, ovary, small intestine, and peripheral blood
CC leukocytes.
CC -!- SIMILARITY: Belongs to the ephrin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00884}.
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DR EMBL; U14187; AAC50078.1; -; mRNA.
DR EMBL; L37360; AAA52368.1; -; mRNA.
DR EMBL; AK316248; BAH14619.1; -; mRNA.
DR EMBL; AL691442; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53137.1; -; Genomic_DNA.
DR EMBL; BC017722; AAH17722.1; -; mRNA.
DR EMBL; BC110406; AAI10407.1; -; mRNA.
DR CCDS; CCDS1090.1; -. [P52797-1]
DR PIR; I38849; I38849.
DR RefSeq; NP_004943.1; NM_004952.4. [P52797-1]
DR AlphaFoldDB; P52797; -.
DR SMR; P52797; -.
DR BioGRID; 108264; 8.
DR IntAct; P52797; 6.
DR STRING; 9606.ENSP00000357393; -.
DR GlyConnect; 1210; 14 N-Linked glycans (2 sites).
DR GlyGen; P52797; 3 sites, 13 N-linked glycans (2 sites).
DR PhosphoSitePlus; P52797; -.
DR BioMuta; EFNA3; -.
DR EPD; P52797; -.
DR jPOST; P52797; -.
DR MassIVE; P52797; -.
DR PaxDb; P52797; -.
DR PeptideAtlas; P52797; -.
DR PRIDE; P52797; -.
DR ProteomicsDB; 56535; -. [P52797-1]
DR Antibodypedia; 4186; 357 antibodies from 31 providers.
DR DNASU; 1944; -.
DR Ensembl; ENST00000368408.4; ENSP00000357393.3; ENSG00000143590.14. [P52797-1]
DR GeneID; 1944; -.
DR KEGG; hsa:1944; -.
DR MANE-Select; ENST00000368408.4; ENSP00000357393.3; NM_004952.5; NP_004943.1.
DR UCSC; uc001fhf.3; human. [P52797-1]
DR CTD; 1944; -.
DR DisGeNET; 1944; -.
DR GeneCards; EFNA3; -.
DR HGNC; HGNC:3223; EFNA3.
DR HPA; ENSG00000143590; Tissue enhanced (esophagus, skin).
DR MIM; 601381; gene.
DR neXtProt; NX_P52797; -.
DR OpenTargets; ENSG00000143590; -.
DR PharmGKB; PA27658; -.
DR VEuPathDB; HostDB:ENSG00000143590; -.
DR eggNOG; KOG3858; Eukaryota.
DR GeneTree; ENSGT00940000161355; -.
DR HOGENOM; CLU_081598_1_0_1; -.
DR InParanoid; P52797; -.
DR OMA; EYNPFVP; -.
DR OrthoDB; 1094764at2759; -.
DR PhylomeDB; P52797; -.
DR PathwayCommons; P52797; -.
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; P52797; -.
DR SIGNOR; P52797; -.
DR BioGRID-ORCS; 1944; 59 hits in 1068 CRISPR screens.
DR GeneWiki; EFNA3; -.
DR GenomeRNAi; 1944; -.
DR Pharos; P52797; Tbio.
DR PRO; PR:P52797; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P52797; protein.
DR Bgee; ENSG00000143590; Expressed in skin of leg and 163 other tissues.
DR Genevisible; P52797; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; TAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; TAS:ProtInc.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:BHF-UCL.
DR GO; GO:1902961; P:positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; IGI:ARUK-UCL.
DR GO; GO:0045664; P:regulation of neuron differentiation; 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 Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW GPI-anchor; Lipoprotein; Membrane; Reference proteome; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..214
FT /note="Ephrin-A3"
FT /id="PRO_0000008369"
FT PROPEP 215..238
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000008370"
FT DOMAIN 30..169
FT /note="Ephrin RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT LIPID 214
FT /note="GPI-anchor amidated glycine"
FT /evidence="ECO:0000255"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 63..110
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT DISULFID 99..158
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT VAR_SEQ 170..196
FT /note="TSHSGEKPVPTLPQFTMGPNVKINVLE -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055483"
FT VARIANT 190
FT /note="V -> M (in dbSNP:rs17723260)"
FT /id="VAR_048937"
FT CONFLICT 71..74
FT /note="Missing (in Ref. 2; AAA52368)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 238 AA; 26350 MW; 8EFD6AE8FE33FDDA CRC64;
MAAAPLLLLL LLVPVPLLPL LAQGPGGALG NRHAVYWNSS NQHLRREGYT VQVNVNDYLD
IYCPHYNSSG VGPGAGPGPG GGAEQYVLYM VSRNGYRTCN ASQGFKRWEC NRPHAPHSPI
KFSEKFQRYS AFSLGYEFHA GHEYYYISTP THNLHWKCLR MKVFVCCAST SHSGEKPVPT
LPQFTMGPNV KINVLEDFEG ENPQVPKLEK SISGTSPKRE HLPLAVGIAF FLMTFLAS
