EFNB2_MOUSE
ID EFNB2_MOUSE Reviewed; 336 AA.
AC P52800;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Ephrin-B2;
DE AltName: Full=ELF-2;
DE AltName: Full=EPH-related receptor tyrosine kinase ligand 5;
DE Short=LERK-5;
DE AltName: Full=HTK ligand;
DE Short=HTK-L;
DE Flags: Precursor;
GN Name=Efnb2; Synonyms=Elf2, Epl5, Eplg5, Htkl, Lerk5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8559144; DOI=10.1016/0161-5890(95)00108-5;
RA Cerretti D.P., Vanden Bos T., Nelson N., Kozlosky C.J., Reddy P.,
RA Maraskovsky E., Park L.S., Lyman S.D., Copeland N.G., Gilbert D.J.,
RA Jenkins N.A., Fletcher R.A.;
RT "Isolation of LERK-5: a ligand of the eph-related receptor tyrosine
RT kinases.";
RL Mol. Immunol. 32:1197-1205(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CB57BL/6J X SJL/J;
RX PubMed=7534404; DOI=10.1073/pnas.92.6.1866;
RA Bennett B.D., Zeigler F.C., Gu Q., Fendly B., Goddard A.D., Gillett N.,
RA Matthews W.;
RT "Molecular cloning of a ligand for the EPH-related receptor protein-
RT tyrosine kinase Htk.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:1866-1870(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=ICR; TISSUE=Brain;
RX PubMed=7651410; DOI=10.1128/mcb.15.9.4921;
RA Bergemann A.D., Cheng H.J., Brambilla R., Klein R., Flanagan J.G.;
RT "ELF-2, a new member of the Eph ligand family, is segmentally expressed in
RT mouse embryos in the region of the hindbrain and newly forming somites.";
RL Mol. Cell. Biol. 15:4921-4929(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; 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 [5]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10704386; DOI=10.1242/dev.127.7.1397;
RA Imondi R., Wideman C., Kaprielian Z.;
RT "Complementary expression of transmembrane ephrins and their receptors in
RT the mouse spinal cord: a possible role in constraining the orientation of
RT longitudinally projecting axons.";
RL Development 127:1397-1410(2000).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263 AND THR-277, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-280, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [8]
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=27446912; DOI=10.3389/fcell.2016.00058;
RA Alonso-Martin S., Rochat A., Mademtzoglou D., Morais J., de Reynies A.,
RA Aurade F., Chang T.H., Zammit P.S., Relaix F.;
RT "Gene expression profiling of muscle stem cells identifies novel regulators
RT of postnatal myogenesis.";
RL Front. Cell Dev. Biol. 4:58-58(2016).
RN [9]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=30639848; DOI=10.1016/j.isci.2018.12.017;
RA Defourny J., Peuckert C., Kullander K., Malgrange B.;
RT "EphA4-ADAM10 Interplay Patterns the Cochlear Sensory Epithelium through
RT Local Disruption of Adherens Junctions.";
RL IScience 11:246-257(2019).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 30-207, DISULFIDE BONDS, AND
RP GLYCOSYLATION AT ASN-39.
RX PubMed=11703926; DOI=10.1016/s1534-5807(01)00002-8;
RA Toth J., Cutforth T., Gelinas A.D., Bethoney K.A., Bard J., Harrison C.J.;
RT "Crystal structure of an ephrin ectodomain.";
RL Dev. Cell 1:83-92(2001).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 31-168 IN COMPLEX WITH EPHB2, AND
RP DISULFIDE BOND.
RX PubMed=11780069; DOI=10.1038/414933a;
RA Himanen J.-P., Rajashankar K.R., Lackmann M., Cowan C.A., Henkemeyer M.,
RA Nikolov D.B.;
RT "Crystal structure of an Eph receptor-ephrin complex.";
RL Nature 414:933-938(2001).
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. Binds to receptor tyrosine
CC kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 plays a
CC central role in heart morphogenesis and angiogenesis through regulation
CC of cell adhesion and cell migration. EPHB4-mediated forward signaling
CC controls cellular repulsion and segregation from EFNB2-expressing
CC cells. May play a role in constraining the orientation of
CC longitudinally projecting axons. {ECO:0000269|PubMed:10704386}.
CC -!- SUBUNIT: Interacts with PDZRN3. Binds to the ephrin receptor EPHA3,
CC EPHA4 and EPHB4 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P52800; Q03137: Epha4; NbExp=2; IntAct=EBI-1032676, EBI-1539152;
CC P52800; O88797: Dab2; Xeno; NbExp=2; IntAct=EBI-1032676, EBI-6109302;
CC P52800; P12931: SRC; Xeno; NbExp=2; IntAct=EBI-1032676, EBI-621482;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P52799};
CC Single-pass type I membrane protein {ECO:0000255}. Cell junction,
CC adherens junction {ECO:0000269|PubMed:30639848}.
CC -!- TISSUE SPECIFICITY: Expressed in inner and outer pillar cells of the
CC organ of Corti (at protein level) (PubMed:30639848). Expressed on
CC lateral floor plate cells, specifically on commissural axon segments
CC that have passed through the floor plate. Expressed in cells of the
CC retinal ganglion cell layer during retinal axon guidance to the optic
CC disk (PubMed:7651410, PubMed:10704386). Expressed in myogenic
CC progenitor cells (PubMed:27446912). {ECO:0000269|PubMed:10704386,
CC ECO:0000269|PubMed:27446912, ECO:0000269|PubMed:30639848,
CC ECO:0000269|PubMed:7651410}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the floor plate throughout the period
CC of commissural axon pathfinding (PubMed:7651410, PubMed:10704386). In
CC myogenic progenitor cells, highly expressed during early development
CC (11.5 dpc) and progressively repressed as developments proceeds
CC (PubMed:27446912). {ECO:0000269|PubMed:10704386,
CC ECO:0000269|PubMed:27446912, ECO:0000269|PubMed:7651410}.
CC -!- PTM: Inducible phosphorylation of tyrosine residues in the cytoplasmic
CC domain. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ephrin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00884}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC42052.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U16819; AAA99708.1; -; mRNA.
DR EMBL; L38847; AAC42052.1; ALT_INIT; mRNA.
DR EMBL; U30244; AAA82934.1; -; mRNA.
DR EMBL; BC057009; AAH57009.1; -; mRNA.
DR CCDS; CCDS22090.1; -.
DR PIR; I49766; I49766.
DR RefSeq; NP_034241.2; NM_010111.5.
DR PDB; 1IKO; X-ray; 1.92 A; P=30-207.
DR PDB; 1KGY; X-ray; 2.70 A; E/F/G/H=31-168.
DR PDBsum; 1IKO; -.
DR PDBsum; 1KGY; -.
DR AlphaFoldDB; P52800; -.
DR BMRB; P52800; -.
DR SMR; P52800; -.
DR BioGRID; 199395; 7.
DR DIP; DIP-29208N; -.
DR IntAct; P52800; 17.
DR MINT; P52800; -.
DR STRING; 10090.ENSMUSP00000001319; -.
DR GlyConnect; 2294; 1 N-Linked glycan (1 site).
DR GlyGen; P52800; 2 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P52800; -.
DR PhosphoSitePlus; P52800; -.
DR PaxDb; P52800; -.
DR PeptideAtlas; P52800; -.
DR PRIDE; P52800; -.
DR ProteomicsDB; 277770; -.
DR ABCD; P52800; 34 sequenced antibodies.
DR Antibodypedia; 2406; 525 antibodies from 45 providers.
DR DNASU; 13642; -.
DR Ensembl; ENSMUST00000001319; ENSMUSP00000001319; ENSMUSG00000001300.
DR GeneID; 13642; -.
DR KEGG; mmu:13642; -.
DR UCSC; uc009kue.1; mouse.
DR CTD; 1948; -.
DR MGI; MGI:105097; Efnb2.
DR VEuPathDB; HostDB:ENSMUSG00000001300; -.
DR eggNOG; KOG3858; Eukaryota.
DR GeneTree; ENSGT00940000155868; -.
DR HOGENOM; CLU_072080_0_0_1; -.
DR InParanoid; P52800; -.
DR OMA; GSTRHND; -.
DR OrthoDB; 903831at2759; -.
DR PhylomeDB; P52800; -.
DR Reactome; R-MMU-2682334; EPH-Ephrin signaling.
DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling.
DR Reactome; R-MMU-3928664; Ephrin signaling.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR BioGRID-ORCS; 13642; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Elf2; mouse.
DR EvolutionaryTrace; P52800; -.
DR PRO; PR:P52800; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P52800; protein.
DR Bgee; ENSMUSG00000001300; Expressed in lumbar dorsal root ganglion and 291 other tissues.
DR ExpressionAtlas; P52800; baseline and differential.
DR Genevisible; P52800; MM.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0046875; F:ephrin receptor binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IPI:MGI.
DR GO; GO:0034332; P:adherens junction organization; IDA:ARUK-UCL.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:MGI.
DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043616; P:keratinocyte proliferation; IMP:MGI.
DR GO; GO:0001945; P:lymph vessel development; IMP:MGI.
DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; IMP:MGI.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISO:MGI.
DR GO; GO:0072178; P:nephric duct morphogenesis; IMP:MGI.
DR GO; GO:1903849; P:positive regulation of aorta morphogenesis; IMP:MGI.
DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; IMP:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:MGI.
DR GO; GO:0099054; P:presynapse assembly; ISO:MGI.
DR GO; GO:0050920; P:regulation of chemotaxis; ISS:UniProtKB.
DR GO; GO:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; IDA:SynGO.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IDA:SynGO.
DR GO; GO:0031295; P:T cell costimulation; IDA:MGI.
DR GO; GO:0048845; P:venous blood vessel morphogenesis; IMP:MGI.
DR CDD; cd10426; Ephrin-B_Ectodomain; 1.
DR Gene3D; 2.60.40.420; -; 1.
DR InterPro; IPR008972; Cupredoxin.
DR InterPro; IPR031328; Ephrin.
DR InterPro; IPR034255; Ephrin-B_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; Angiogenesis; Cell junction; Cell membrane;
KW Developmental protein; Differentiation; Disulfide bond; Glycoprotein;
KW Membrane; Methylation; Neurogenesis; Phosphoprotein; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..336
FT /note="Ephrin-B2"
FT /id="PRO_0000008393"
FT TOPO_DOM 29..232
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..336
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 31..167
FT /note="Ephrin RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT REGION 170..216
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 334..336
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 190..216
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 277
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 280
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:11703926"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 65..104
FT /evidence="ECO:0000269|PubMed:11703926,
FT ECO:0000269|PubMed:11780069, ECO:0007744|PDB:1IKO"
FT DISULFID 92..156
FT /evidence="ECO:0000269|PubMed:11703926,
FT ECO:0000269|PubMed:11780069, ECO:0007744|PDB:1IKO"
FT CONFLICT 177
FT /note="A -> T (in Ref. 1; AAA99708)"
FT /evidence="ECO:0000305"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:1IKO"
FT STRAND 50..53
FT /evidence="ECO:0007829|PDB:1IKO"
FT STRAND 60..64
FT /evidence="ECO:0007829|PDB:1IKO"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:1IKO"
FT STRAND 78..84
FT /evidence="ECO:0007829|PDB:1IKO"
FT HELIX 86..91
FT /evidence="ECO:0007829|PDB:1IKO"
FT STRAND 101..104
FT /evidence="ECO:0007829|PDB:1IKO"
FT STRAND 112..116
FT /evidence="ECO:0007829|PDB:1IKO"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:1IKO"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:1IKO"
FT HELIX 154..158
FT /evidence="ECO:0007829|PDB:1IKO"
FT STRAND 162..167
FT /evidence="ECO:0007829|PDB:1IKO"
SQ SEQUENCE 336 AA; 37202 MW; D08894996E399554 CRC64;
MAMARSRRDS VWKYCWGLLM VLCRTAISRS IVLEPIYWNS SNSKFLPGQG LVLYPQIGDK
LDIICPKVDS KTVGQYEYYK VYMVDKDQAD RCTIKKENTP LLNCARPDQD VKFTIKFQEF
SPNLWGLEFQ KNKDYYIIST SNGSLEGLDN QEGGVCQTRA MKILMKVGQD ASSAGSARNH
GPTRRPELEA GTNGRSSTTS PFVKPNPGSS TDGNSAGHSG NNLLGSEVAL FAGIASGCII
FIVIIITLVV LLLKYRRRHR KHSPQHTTTL SLSTLATPKR GGNNNGSEPS DVIIPLRTAD
SVFCPHYEKV SGDYGHPVYI VQEMPPQSPA NIYYKV
