SEM4A_MOUSE
ID SEM4A_MOUSE Reviewed; 760 AA.
AC Q62178; D3Z5L2;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Semaphorin-4A;
DE AltName: Full=Semaphorin-B;
DE Short=Sema B;
DE Flags: Precursor;
GN Name=Sema4a; Synonyms=Semab, SemB;
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].
RC STRAIN=NMRI; TISSUE=Brain;
RX PubMed=7748561; DOI=10.1016/0896-6273(95)90332-1;
RA Pueschel A.W., Adams R.H., Betz H.;
RT "Murine semaphorin D/collapsin is a member of a diverse gene family and
RT creates domains inhibitory for axonal extension.";
RL Neuron 14:941-948(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TIMD2.
RX PubMed=12374982; DOI=10.1038/nature01037;
RA Kumanogoh A., Marukawa S., Suzuki K., Takegahara N., Watanabe C., Ch'ng E.,
RA Ishida I., Fujimura H., Sakoda S., Yoshida K., Kikutani H.;
RT "Class IV semaphorin Sema4A enhances T-cell activation and interacts with
RT Tim-2.";
RL Nature 419:629-633(2002).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=15277503; DOI=10.1167/iovs.04-0020;
RA Rice D.S., Huang W., Jones H.A., Hansen G., Ye G.L., Xu N., Wilson E.A.,
RA Troughton K., Vaddi K., Newton R.C., Zambrowicz B.P., Sands A.T.;
RT "Severe retinal degeneration associated with disruption of semaphorin 4A.";
RL Invest. Ophthalmol. Vis. Sci. 45:2767-2777(2004).
RN [6]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=15780988; DOI=10.1016/j.immuni.2005.01.014;
RA Kumanogoh A., Shikina T., Suzuki K., Uematsu S., Yukawa K., Kashiwamura S.,
RA Tsutsui H., Yamamoto M., Takamatsu H., Ko-Mitamura E.P., Takegahara N.,
RA Marukawa S., Ishida I., Morishita H., Prasad D.V., Tamura M., Mizui M.,
RA Toyofuku T., Akira S., Takeda K., Okabe M., Kikutani H.;
RT "Nonredundant roles of Sema4A in the immune system: defective T cell
RT priming and Th1/Th2 regulation in Sema4A-deficient mice.";
RL Immunity 22:305-316(2005).
RN [7]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP PLXND1.
RX PubMed=17318185; DOI=10.1038/sj.emboj.7601589;
RA Toyofuku T., Yabuki M., Kamei J., Kamei M., Makino N., Kumanogoh A.,
RA Hori M.;
RT "Semaphorin-4A, an activator for T-cell-mediated immunity, suppresses
RT angiogenesis via plexin-D1.";
RL EMBO J. 26:1373-1384(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, 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 [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PLXNB1; PLXNB2 AND
RP PLXNB3.
RX PubMed=20043131;
RA Yukawa K., Tanaka T., Yoshida K., Takeuchi N., Ito T., Takamatsu H.,
RA Kikutani H., Kumanogoh A.;
RT "Sema4A induces cell morphological changes through B-type plexin-mediated
RT signaling.";
RL Int. J. Mol. Med. 25:225-230(2010).
RN [12]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=29981480; DOI=10.1016/j.mcn.2018.06.008;
RA McDermott J.E., Goldblatt D., Paradis S.;
RT "Class 4 Semaphorins and Plexin-B receptors regulate GABAergic and
RT glutamatergic synapse development in the mammalian hippocampus.";
RL Mol. Cell. Neurosci. 92:50-66(2018).
CC -!- FUNCTION: Cell surface receptor for PLXNB1, PLXNB2, PLXNB3 and PLXND1
CC that plays an important role in cell-cell signaling (PubMed:20043131,
CC PubMed:17318185). Regulates glutamatergic and GABAergic synapse
CC development (PubMed:29981480). Promotes the development of inhibitory
CC synapses in a PLXNB1-dependent manner and promotes the development of
CC excitatory synapses in a PLXNB2-dependent manner (PubMed:29981480).
CC Plays a role in priming antigen-specific T-cells, promotes
CC differentiation of Th1 T-helper cells, and thereby contributes to
CC adaptive immunity (PubMed:15780988). Promotes phosphorylation of TIMD2
CC (PubMed:12374982). Inhibits angiogenesis (PubMed:17318185). Promotes
CC axon growth cone collapse (PubMed:20043131). Inhibits axonal extension
CC by providing local signals to specify territories inaccessible for
CC growing axons (PubMed:20043131). {ECO:0000269|PubMed:12374982,
CC ECO:0000269|PubMed:15780988, ECO:0000269|PubMed:17318185,
CC ECO:0000269|PubMed:20043131, ECO:0000269|PubMed:29981480}.
CC -!- SUBUNIT: Interacts with PLXNB1, PLXNB2 and PLXNB3 (PubMed:20043131).
CC Interacts with PLXND1 (PubMed:17318185). Interacts with TIMD2
CC (PubMed:12374982). {ECO:0000269|PubMed:12374982,
CC ECO:0000269|PubMed:17318185, ECO:0000269|PubMed:20043131}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12374982,
CC ECO:0000269|PubMed:15780988, ECO:0000269|PubMed:17318185,
CC ECO:0000269|PubMed:20043131}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in neurons and glia in the developing
CC hippocampus. {ECO:0000269|PubMed:29981480}.
CC -!- DEVELOPMENTAL STAGE: Expressed from day 10 in the embryo. Low levels
CC found between days 10-12. Expression peaks on day 13 with moderate
CC levels from then until birth.
CC -!- DISRUPTION PHENOTYPE: Results are contradictory; one study
CC (PubMed:15780988) finds no visible phenotype; mice are born at the
CC expected Mendelian ratio and are fertile, but they present defects in
CC T-cell differentiation and in T-cell responses to antigens. According
CC to another publication (PubMed:15277503) gene disruption leads to
CC degeneration of photoreceptor cells in the retina within the first
CC month of life. {ECO:0000269|PubMed:15277503,
CC ECO:0000269|PubMed:15780988, ECO:0000269|PubMed:17318185}.
CC -!- SIMILARITY: Belongs to the semaphorin family. {ECO:0000305}.
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DR EMBL; X85991; CAA59983.1; -; mRNA.
DR EMBL; AC102388; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466547; EDL15277.1; -; Genomic_DNA.
DR EMBL; CH466547; EDL15278.1; -; Genomic_DNA.
DR EMBL; CH466547; EDL15279.1; -; Genomic_DNA.
DR CCDS; CCDS17475.1; -.
DR PIR; I48745; I48745.
DR RefSeq; NP_001156961.1; NM_001163489.1.
DR RefSeq; NP_001156962.1; NM_001163490.1.
DR RefSeq; NP_001156963.1; NM_001163491.1.
DR RefSeq; NP_038686.3; NM_013658.3.
DR RefSeq; XP_006501252.1; XM_006501189.1.
DR RefSeq; XP_011238353.1; XM_011240051.1.
DR AlphaFoldDB; Q62178; -.
DR SMR; Q62178; -.
DR BioGRID; 203166; 7.
DR STRING; 10090.ENSMUSP00000029700; -.
DR GlyConnect; 2696; 4 N-Linked glycans (1 site).
DR GlyGen; Q62178; 4 sites, 4 N-linked glycans (1 site).
DR iPTMnet; Q62178; -.
DR PhosphoSitePlus; Q62178; -.
DR SwissPalm; Q62178; -.
DR EPD; Q62178; -.
DR MaxQB; Q62178; -.
DR PaxDb; Q62178; -.
DR PeptideAtlas; Q62178; -.
DR PRIDE; Q62178; -.
DR ProteomicsDB; 256615; -.
DR Antibodypedia; 20428; 350 antibodies from 33 providers.
DR DNASU; 20351; -.
DR Ensembl; ENSMUST00000029700; ENSMUSP00000029700; ENSMUSG00000028064.
DR Ensembl; ENSMUST00000165898; ENSMUSP00000128510; ENSMUSG00000028064.
DR Ensembl; ENSMUST00000166237; ENSMUSP00000125909; ENSMUSG00000028064.
DR Ensembl; ENSMUST00000169222; ENSMUSP00000128887; ENSMUSG00000028064.
DR GeneID; 20351; -.
DR KEGG; mmu:20351; -.
DR UCSC; uc008pvg.2; mouse.
DR CTD; 64218; -.
DR MGI; MGI:107560; Sema4a.
DR VEuPathDB; HostDB:ENSMUSG00000028064; -.
DR eggNOG; KOG3611; Eukaryota.
DR GeneTree; ENSGT00940000161509; -.
DR InParanoid; Q62178; -.
DR OMA; KYYAGDG; -.
DR OrthoDB; 64683at2759; -.
DR PhylomeDB; Q62178; -.
DR TreeFam; TF316102; -.
DR Reactome; R-MMU-416700; Other semaphorin interactions.
DR BioGRID-ORCS; 20351; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Sema4a; mouse.
DR PRO; PR:Q62178; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q62178; protein.
DR Bgee; ENSMUSG00000028064; Expressed in granulocyte and 254 other tissues.
DR ExpressionAtlas; Q62178; baseline and differential.
DR Genevisible; Q62178; MM.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045499; F:chemorepellent activity; IBA:GO_Central.
DR GO; GO:0030215; F:semaphorin receptor binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007409; P:axonogenesis; IMP:UniProtKB.
DR GO; GO:0050919; P:negative chemotaxis; IBA:GO_Central.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IBA:GO_Central.
DR GO; GO:0001755; P:neural crest cell migration; IBA:GO_Central.
DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central.
DR GO; GO:1904891; P:positive regulation of excitatory synapse assembly; IMP:UniProtKB.
DR GO; GO:1905704; P:positive regulation of inhibitory synapse assembly; IMP:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IDA:UniProtKB.
DR GO; GO:0010594; P:regulation of endothelial cell migration; IMP:UniProtKB.
DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; IDA:UniProtKB.
DR GO; GO:0002292; P:T cell differentiation involved in immune response; IMP:UniProtKB.
DR GO; GO:0045063; P:T-helper 1 cell differentiation; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR002165; Plexin_repeat.
DR InterPro; IPR016201; PSI.
DR InterPro; IPR001627; Semap_dom.
DR InterPro; IPR036352; Semap_dom_sf.
DR InterPro; IPR027231; Semaphorin.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR PANTHER; PTHR11036; PTHR11036; 1.
DR Pfam; PF01437; PSI; 1.
DR Pfam; PF01403; Sema; 1.
DR SMART; SM00423; PSI; 1.
DR SMART; SM00630; Sema; 1.
DR SUPFAM; SSF101912; SSF101912; 1.
DR PROSITE; PS51004; SEMA; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Angiogenesis; Cell membrane; Developmental protein;
KW Differentiation; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Membrane; Neurogenesis; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..760
FT /note="Semaphorin-4A"
FT /id="PRO_0000032323"
FT TOPO_DOM 33..682
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 683..703
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 704..760
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 36..494
FT /note="Sema"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DOMAIN 496..547
FT /note="PSI"
FT DOMAIN 572..630
FT /note="Ig-like C2-type"
FT REGION 720..760
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 727..748
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 120
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 496
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 606
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 113..124
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 142..151
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 269..379
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 293..339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 497..514
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 506..523
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 579..623
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT CONFLICT 83
FT /note="A -> T (in Ref. 1; CAA59983)"
FT /evidence="ECO:0000305"
FT CONFLICT 178..185
FT /note="FDPVHKHT -> LTLFTSTQ (in Ref. 1; CAA59983)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="Q -> H (in Ref. 1; CAA59983)"
FT /evidence="ECO:0000305"
FT CONFLICT 442
FT /note="S -> P (in Ref. 1; CAA59983)"
FT /evidence="ECO:0000305"
FT CONFLICT 578
FT /note="P -> R (in Ref. 1; CAA59983)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 760 AA; 83421 MW; C13BD31BD90BE3D9 CRC64;
MALPSLGQDS WSLLRVFFFQ LFLLPSLPPA SGTGGQGPMP RVKYHAGDGH RALSFFQQKG
LRDFDTLLLS DDGNTLYVGA REAVLALNIQ NPGIPRLKNM IPWPASERKK TECAFKKKSN
ETQCFNFIRV LVSYNATHLY ACGTFAFSPA CTFIELQDSL LLPILIDKVM DGKGQSPFDP
VHKHTAVLVD GMLYSGTMNN FLGSEPILMR TLGSQPVLKT DIFLRWLHAD ASFVAAIPST
QVVYFFFEET ASEFDFFEEL YISRVAQVCK NDVGGEKLLQ KKWTTFLKAQ LLCAQPGQLP
FNIIRHAVLL PADSPSVSRI YAVFTSQWQV GGTRSSAVCA FSLTDIERVF KGKYKELNKE
TSRWTTYRGS EVSPRPGSCS MGPSSDKALT FMKDHFLMDE HVVGTPLLVK SGVEYTRLAV
ESARGLDGSS HVVMYLGTST GSLHKAVVPQ DSSAYLVEEI QLSPDSEPVR NLQLAPAQGA
VFAGFSGGIW RVPRANCSVY ESCVDCVLAR DPHCAWDPES RLCSLLSGST KPWKQDMERG
NPEWVCTRGP MARSPRRQSP PQLIKEVLTV PNSILELPCP HLSALASYHW SHGRAKISEA
SATVYNGSLL LLPQDGVGGL YQCVATENGY SYPVVSYWVD SQDQPLALDP ELAGVPRERV
QVPLTRVGGG ASMAAQRSYW PHFLIVTVLL AIVLLGVLTL LLASPLGALR ARGKVQGCGM
LPPREKAPLS RDQHLQPSKD HRTSASDVDA DNNHLGAEVA
