EFNB3_HUMAN
ID EFNB3_HUMAN Reviewed; 340 AA.
AC Q15768; B2RBW2; D3DTQ6; O00680; Q8TBH7; Q92875;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Ephrin-B3;
DE AltName: Full=EPH-related receptor transmembrane ligand ELK-L3;
DE AltName: Full=EPH-related receptor tyrosine kinase ligand 8;
DE Short=LERK-8;
DE Flags: Precursor;
GN Name=EFNB3; Synonyms=EPLG8, LERK8;
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].
RA Cerretti D.P.;
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9126477; DOI=10.1006/geno.1997.4615;
RA Tang X.X., Pleasure D.E., Ikegaki N.;
RT "cDNA cloning, chromosomal localization, and expression pattern of EPLG8, a
RT new member of the EPLG gene family encoding ligands of EPH-related protein-
RT tyrosine kinase receptors.";
RL Genomics 41:17-24(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain cortex;
RX PubMed=8808709;
RA Gale N.W., Flenniken A., Compton D.C., Jenkins N.A., Copeland N.G.,
RA Gilbert D.J., Davis S., Wilkinson D.G., Yancopoulos G.D.;
RT "Elk-L3, a novel transmembrane ligand for the Eph family of receptor
RT tyrosine kinases, expressed in embryonic floor plate, roof plate and
RT hindbrain segments.";
RL Oncogene 13:1343-1352(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [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].
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 [7]
RP PROTEIN SEQUENCE OF 28-42.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [8]
RP INTERACTION WITH GRIP1 AND GRIP2.
RC TISSUE=Fetal brain;
RX PubMed=10197531; DOI=10.1016/s0896-6273(00)80706-0;
RA Brueckner K., Pablo Labrador J., Scheiffele P., Herb A., Seeburg P.H.,
RA Klein R.;
RT "EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft
RT membrane microdomains.";
RL Neuron 22:511-524(1999).
RN [9]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH NIPAH VIRUS PROTEIN G, AND
RP MUTAGENESIS OF 124-LEU-TRP-125.
RX PubMed=16477309; DOI=10.1371/journal.ppat.0020007;
RA Negrete O.A., Wolf M.C., Aguilar H.C., Enterlein S., Wang W.,
RA Muehlberger E., Su S.V., Bertolotti-Ciarlet A., Flick R., Lee B.;
RT "Two key residues in ephrinB3 are critical for its use as an alternative
RT receptor for Nipah virus.";
RL PLoS Pathog. 2:78-86(2006).
RN [10]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HENDRA VIRUS
RP GLYCOPROTEIN.
RX PubMed=17376907; DOI=10.1128/jvi.02022-06;
RA Bishop K.A., Stantchev T.S., Hickey A.C., Khetawat D., Bossart K.N.,
RA Krasnoperov V., Gill P., Feng Y.R., Wang L., Eaton B.T., Wang L.F.,
RA Broder C.C.;
RT "Identification of Hendra virus G glycoprotein residues that are critical
RT for receptor binding.";
RL J. Virol. 81:5893-5901(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-274, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Cell surface transmembrane ligand for Eph receptors, a family
CC of 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. May play a pivotal role in
CC forebrain function. Binds to, and induce the collapse of, commissural
CC axons/growth cones in vitro. May play a role in constraining the
CC orientation of longitudinally projecting axons (By similarity).
CC {ECO:0000250}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for nipah virus and
CC hendra virus. {ECO:0000269|PubMed:16477309,
CC ECO:0000269|PubMed:17376907}.
CC -!- SUBUNIT: Interacts with GRIP1 and GRIP2. {ECO:0000269|PubMed:10197531}.
CC -!- SUBUNIT: (Microbial infection) Interacts with nipah virus and hendra
CC virus glycoprotein (PubMed:16477309, PubMed:17376907).
CC {ECO:0000269|PubMed:16477309, ECO:0000269|PubMed:17376907}.
CC -!- INTERACTION:
CC Q15768; P54764: EPHA4; NbExp=2; IntAct=EBI-3908475, EBI-5773557;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain; expressed in embryonic
CC floor plate, roof plate and hindbrain segments.
CC -!- SIMILARITY: Belongs to the ephrin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00884}.
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DR EMBL; U57001; AAB05170.1; -; mRNA.
DR EMBL; U66406; AAC51203.1; -; mRNA.
DR EMBL; U62775; AAC50707.1; -; mRNA.
DR EMBL; AK314841; BAG37359.1; -; mRNA.
DR EMBL; CH471108; EAW90133.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90135.1; -; Genomic_DNA.
DR EMBL; BC022499; AAH22499.1; -; mRNA.
DR EMBL; BC042944; AAH42944.1; -; mRNA.
DR CCDS; CCDS11120.1; -.
DR RefSeq; NP_001397.1; NM_001406.3.
DR PDB; 4BKF; X-ray; 4.65 A; C/D=27-169.
DR PDBsum; 4BKF; -.
DR AlphaFoldDB; Q15768; -.
DR SMR; Q15768; -.
DR BioGRID; 108269; 142.
DR DIP; DIP-59196N; -.
DR IntAct; Q15768; 38.
DR MINT; Q15768; -.
DR STRING; 9606.ENSP00000226091; -.
DR GlyGen; Q15768; 1 site.
DR iPTMnet; Q15768; -.
DR PhosphoSitePlus; Q15768; -.
DR BioMuta; EFNB3; -.
DR DMDM; 2494367; -.
DR EPD; Q15768; -.
DR MassIVE; Q15768; -.
DR PaxDb; Q15768; -.
DR PeptideAtlas; Q15768; -.
DR PRIDE; Q15768; -.
DR ProteomicsDB; 60749; -.
DR Antibodypedia; 644; 299 antibodies from 30 providers.
DR DNASU; 1949; -.
DR Ensembl; ENST00000226091.3; ENSP00000226091.2; ENSG00000108947.5.
DR GeneID; 1949; -.
DR KEGG; hsa:1949; -.
DR MANE-Select; ENST00000226091.3; ENSP00000226091.2; NM_001406.4; NP_001397.1.
DR UCSC; uc002gis.4; human.
DR CTD; 1949; -.
DR DisGeNET; 1949; -.
DR GeneCards; EFNB3; -.
DR HGNC; HGNC:3228; EFNB3.
DR HPA; ENSG00000108947; Tissue enhanced (brain).
DR MIM; 602297; gene.
DR neXtProt; NX_Q15768; -.
DR OpenTargets; ENSG00000108947; -.
DR PharmGKB; PA27663; -.
DR VEuPathDB; HostDB:ENSG00000108947; -.
DR eggNOG; KOG3858; Eukaryota.
DR GeneTree; ENSGT00940000160323; -.
DR HOGENOM; CLU_072080_0_0_1; -.
DR InParanoid; Q15768; -.
DR OMA; KESMPGD; -.
DR OrthoDB; 903831at2759; -.
DR PhylomeDB; Q15768; -.
DR PathwayCommons; Q15768; -.
DR Reactome; R-HSA-2682334; EPH-Ephrin signaling.
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-HSA-3928664; Ephrin signaling.
DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells.
DR SignaLink; Q15768; -.
DR SIGNOR; Q15768; -.
DR BioGRID-ORCS; 1949; 14 hits in 1065 CRISPR screens.
DR ChiTaRS; EFNB3; human.
DR GeneWiki; EFNB3; -.
DR GenomeRNAi; 1949; -.
DR Pharos; Q15768; Tbio.
DR PRO; PR:Q15768; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q15768; protein.
DR Bgee; ENSG00000108947; Expressed in middle temporal gyrus and 143 other tissues.
DR Genevisible; Q15768; HS.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:CAFA.
DR GO; GO:0046875; F:ephrin receptor binding; IDA:MGI.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; TAS:ProtInc.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0016198; P:axon choice point recognition; IEA:Ensembl.
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; IDA:MGI.
DR GO; GO:0050771; P:negative regulation of axonogenesis; ISS:ARUK-UCL.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0031295; P:T cell costimulation; IEA:Ensembl.
DR GO; GO:0099557; P:trans-synaptic signaling by trans-synaptic complex, modulating synaptic transmission; IEA:Ensembl.
DR Gene3D; 2.60.40.420; -; 1.
DR InterPro; IPR008972; Cupredoxin.
DR InterPro; IPR031328; Ephrin.
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; Developmental protein; Differentiation;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction; Membrane;
KW Methylation; Neurogenesis; Phosphoprotein; Receptor; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 28..340
FT /note="Ephrin-B3"
FT /id="PRO_0000008395"
FT TOPO_DOM 28..226
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..247
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..340
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..167
FT /note="Ephrin RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT REGION 168..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 254..298
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 338..340
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 182..196
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 271
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O35393"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 62..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT DISULFID 92..156
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT VARIANT 166
FT /note="R -> Q (in dbSNP:rs1165640333)"
FT /id="VAR_002356"
FT MUTAGEN 124..125
FT /note="LW->YM: Complete loss of Nipah protein G binding."
FT /evidence="ECO:0000269|PubMed:16477309"
SQ SEQUENCE 340 AA; 35835 MW; EDFF2A23C2FDE79F CRC64;
MGPPHSGPGG VRVGALLLLG VLGLVSGLSL EPVYWNSANK RFQAEGGYVL YPQIGDRLDL
LCPRARPPGP HSSPNYEFYK LYLVGGAQGR RCEAPPAPNL LLTCDRPDLD LRFTIKFQEY
SPNLWGHEFR SHHDYYIIAT SDGTREGLES LQGGVCLTRG MKVLLRVGQS PRGGAVPRKP
VSEMPMERDR GAAHSLEPGK ENLPGDPTSN ATSRGAEGPL PPPSMPAVAG AAGGLALLLL
GVAGAGGAMC WRRRRAKPSE SRHPGPGSFG RGGSLGLGGG GGMGPREAEP GELGIALRGG
GAADPPFCPH YEKVSGDYGH PVYIVQDGPP QSPPNIYYKV
