SEM4D_MOUSE
ID SEM4D_MOUSE Reviewed; 861 AA.
AC O09126; Q6GTM9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Semaphorin-4D;
DE AltName: Full=M-Sema G;
DE AltName: Full=Semaphorin-C-like 2;
DE AltName: Full=Semaphorin-J;
DE Short=Sema J;
DE AltName: CD_antigen=CD100;
DE Flags: Precursor;
GN Name=Sema4d; Synonyms=Semacl2, Semaj;
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=8969198; DOI=10.1074/jbc.271.52.33376;
RA Furuyama T., Inagaki S., Kosugi A., Noda S., Saitoh S., Ogata M.,
RA Iwahashi Y., Miyazaki N., Hamaoka T., Tohyama M.;
RT "Identification of a novel transmembrane semaphorin expressed on
RT lymphocytes.";
RL J. Biol. Chem. 271:33376-33381(1996).
RN [2]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Limb;
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 [4]
RP FUNCTION, AND INTERACTION WITH PLXNB2.
RX PubMed=17554007; DOI=10.1523/jneurosci.5381-06.2007;
RA Deng S., Hirschberg A., Worzfeld T., Penachioni J.Y., Korostylev A.,
RA Swiercz J.M., Vodrazka P., Mauti O., Stoeckli E.T., Tamagnone L.,
RA Offermanns S., Kuner R.;
RT "Plexin-B2, but not Plexin-B1, critically modulates neuronal migration and
RT patterning of the developing nervous system in vivo.";
RL J. Neurosci. 27:6333-6347(2007).
RN [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-77; ASN-379 AND ASN-419.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-782, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Spleen;
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 FUNCTION.
RX PubMed=23699507; DOI=10.1523/jneurosci.0989-13.2013;
RA Kuzirian M.S., Moore A.R., Staudenmaier E.K., Friedel R.H., Paradis S.;
RT "The class 4 semaphorin Sema4D promotes the rapid assembly of GABAergic
RT synapses in rodent hippocampus.";
RL J. Neurosci. 33:8961-8973(2013).
RN [8]
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 and PLXNB2 that plays an
CC important role in cell-cell signaling (By similarity). Regulates
CC GABAergic synapse development (PubMed:23699507, PubMed:29981480).
CC Promotes the development of inhibitory synapses in a PLXNB1-dependent
CC manner (PubMed:23699507, PubMed:29981480). Modulates the complexity and
CC arborization of developing neurites in hippocampal neurons by
CC activating PLXNB1 and interaction with PLXNB1 mediates activation of
CC RHOA (By similarity). Promotes the migration of cerebellar granule
CC cells (PubMed:17554007). Plays a role in the immune system; induces B-
CC cells to aggregate and improves their viability (in vitro) (By
CC similarity). Induces endothelial cell migration through the activation
CC of PTK2B/PYK2, SRC, and the phosphatidylinositol 3-kinase-AKT pathway
CC (By similarity). {ECO:0000250|UniProtKB:Q92854,
CC ECO:0000269|PubMed:17554007, ECO:0000269|PubMed:23699507,
CC ECO:0000269|PubMed:29981480}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with PLXNB1 (By
CC similarity). Interacts with PLXNB2 (PubMed:17554007).
CC {ECO:0000250|UniProtKB:Q92854, ECO:0000269|PubMed:17554007}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8969198};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in lymphoid tissues, especially
CC in the thymus, as well as in the nervous tissues (PubMed:8969198).
CC Expressed in neurons and glia in the developing hippocampus
CC (PubMed:29981480). {ECO:0000269|PubMed:29981480,
CC ECO:0000269|PubMed:8969198}.
CC -!- SIMILARITY: Belongs to the semaphorin family. {ECO:0000305}.
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DR EMBL; U69535; AAC52964.1; -; mRNA.
DR EMBL; CH466546; EDL41105.1; -; Genomic_DNA.
DR EMBL; CH466546; EDL41106.1; -; Genomic_DNA.
DR EMBL; CH466546; EDL41107.1; -; Genomic_DNA.
DR EMBL; BC049780; AAH49780.2; -; mRNA.
DR CCDS; CCDS26514.1; -.
DR RefSeq; NP_001268809.1; NM_001281880.1.
DR RefSeq; NP_038688.2; NM_013660.4.
DR AlphaFoldDB; O09126; -.
DR SMR; O09126; -.
DR BioGRID; 203169; 5.
DR IntAct; O09126; 1.
DR STRING; 10090.ENSMUSP00000021900; -.
DR GlyConnect; 2698; 7 N-Linked glycans (4 sites).
DR GlyGen; O09126; 8 sites, 7 N-linked glycans (4 sites).
DR iPTMnet; O09126; -.
DR PhosphoSitePlus; O09126; -.
DR SwissPalm; O09126; -.
DR EPD; O09126; -.
DR jPOST; O09126; -.
DR MaxQB; O09126; -.
DR PaxDb; O09126; -.
DR PeptideAtlas; O09126; -.
DR PRIDE; O09126; -.
DR ProteomicsDB; 256617; -.
DR ABCD; O09126; 20 sequenced antibodies.
DR Antibodypedia; 3064; 911 antibodies from 39 providers.
DR DNASU; 20354; -.
DR Ensembl; ENSMUST00000021900; ENSMUSP00000021900; ENSMUSG00000021451.
DR Ensembl; ENSMUST00000110039; ENSMUSP00000105666; ENSMUSG00000021451.
DR Ensembl; ENSMUST00000110040; ENSMUSP00000105667; ENSMUSG00000021451.
DR GeneID; 20354; -.
DR KEGG; mmu:20354; -.
DR UCSC; uc007qmn.2; mouse.
DR CTD; 10507; -.
DR MGI; MGI:109244; Sema4d.
DR VEuPathDB; HostDB:ENSMUSG00000021451; -.
DR eggNOG; KOG3611; Eukaryota.
DR GeneTree; ENSGT00940000159594; -.
DR HOGENOM; CLU_009051_4_0_1; -.
DR InParanoid; O09126; -.
DR OMA; FRQHFFK; -.
DR OrthoDB; 64683at2759; -.
DR PhylomeDB; O09126; -.
DR TreeFam; TF316102; -.
DR Reactome; R-MMU-416550; Sema4D mediated inhibition of cell attachment and migration.
DR Reactome; R-MMU-416572; Sema4D induced cell migration and growth-cone collapse.
DR Reactome; R-MMU-416700; Other semaphorin interactions.
DR BioGRID-ORCS; 20354; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Sema4d; mouse.
DR PRO; PR:O09126; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; O09126; protein.
DR Bgee; ENSMUSG00000021451; Expressed in granulocyte and 244 other tissues.
DR ExpressionAtlas; O09126; baseline and differential.
DR Genevisible; O09126; MM.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; TAS:BHF-UCL.
DR GO; GO:0045499; F:chemorepellent activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030215; F:semaphorin receptor binding; IPI:BHF-UCL.
DR GO; GO:0038023; F:signaling receptor activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IPI:MGI.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007409; P:axonogenesis; IDA:MGI.
DR GO; GO:0070486; P:leukocyte aggregation; ISS:UniProtKB.
DR GO; GO:0050919; P:negative chemotaxis; IBA:GO_Central.
DR GO; GO:0010693; P:negative regulation of alkaline phosphatase activity; IDA:BHF-UCL.
DR GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IBA:GO_Central.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IMP:BHF-UCL.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0001755; P:neural crest cell migration; IBA:GO_Central.
DR GO; GO:0043931; P:ossification involved in bone maturation; IMP:BHF-UCL.
DR GO; GO:0050772; P:positive regulation of axonogenesis; IDA:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL.
DR GO; GO:0048672; P:positive regulation of collateral sprouting; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:BHF-UCL.
DR GO; GO:1905704; P:positive regulation of inhibitory synapse assembly; IDA:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0031344; P:regulation of cell projection organization; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; ISS:UniProtKB.
DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; ISS:UniProtKB.
DR GO; GO:1900220; P:semaphorin-plexin signaling pathway involved in bone trabecula morphogenesis; IMP:BHF-UCL.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
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; PF00047; ig; 1.
DR Pfam; PF01437; PSI; 1.
DR Pfam; PF01403; Sema; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00423; PSI; 1.
DR SMART; SM00630; Sema; 1.
DR SUPFAM; SSF101912; SSF101912; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51004; SEMA; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Developmental protein; Differentiation; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Membrane; Neurogenesis;
KW Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..861
FT /note="Semaphorin-4D"
FT /id="PRO_0000032328"
FT TOPO_DOM 24..733
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 734..754
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 755..861
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..500
FT /note="Sema"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DOMAIN 502..551
FT /note="PSI"
FT DOMAIN 555..636
FT /note="Ig-like C2-type"
FT REGION 649..709
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 793..839
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 655..687
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 695..709
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 822..839
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 782
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 832
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92854"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 419
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 613
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 632
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 97..108
FT /evidence="ECO:0000250"
FT DISULFID 126..135
FT /evidence="ECO:0000250"
FT DISULFID 257..370
FT /evidence="ECO:0000250"
FT DISULFID 281..326
FT /evidence="ECO:0000250"
FT DISULFID 503..520
FT /evidence="ECO:0000250"
FT DISULFID 509..553
FT /evidence="ECO:0000250"
FT DISULFID 512..529
FT /evidence="ECO:0000250"
FT DISULFID 576..624
FT /evidence="ECO:0000250"
FT CONFLICT 470
FT /note="S -> F (in Ref. 1; AAC52964)"
FT /evidence="ECO:0000305"
FT CONFLICT 661
FT /note="A -> V (in Ref. 1; AAC52964)"
FT /evidence="ECO:0000305"
FT CONFLICT 675
FT /note="A -> G (in Ref. 1; AAC52964)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 861 AA; 95640 MW; B962D4E4CF37FFD9 CRC64;
MRMCAPVRGL FLALVVVLRT AVAFAPVPRL TWEHGEVGLV QFHKPGIFNY SALLMSEDKD
TLYVGAREAV FAVNALNISE KQHEVYWKVS EDKKSKCAEK GKSKQTECLN YIRVLQPLSS
TSLYVCGTNA FQPTCDHLNL TSFKFLGKSE DGKGRCPFDP AHSYTSVMVG GELYSGTSYN
FLGSEPIISR NSSHSPLRTE YAIPWLNEPS FVFADVIQKS PDGPEGEDDK VYFFFTEVSV
EYEFVFKLMI PRVARVCKGD QGGLRTLQKK WTSFLKARLI CSKPDSGLVF NILQDVFVLR
APGLKEPVFY AVFTPQLNNV GLSAVCAYTL ATVEAVFSRG KYMQSATVEQ SHTKWVRYNG
PVPTPRPGAC IDSEARAANY TSSLNLPDKT LQFVKDHPLM DDSVTPIDNR PKLIKKDVNY
TQIVVDRTQA LDGTFYDVMF ISTDRGALHK AVILTKEVHV IEETQLFRDS EPVLTLLLSS
KKGRKFVYAG SNSGVVQAPL AFCEKHGSCE DCVLARDPYC AWSPAIKACV TLHQEEASSR
GWIQDMSGDT SSCLDKSKES FNQHFFKHGG TAELKCFQKS NLARVVWKFQ NGELKAASPK
YGFVGRKHLL IFNLSDGDSG VYQCLSEERV RNKTVSQLLA KHVLEVKMVP RTPPSPTSED
AQTEGSKITS KMPVASTQGS SPPTPALWAT SPRAATLPPK SSSGTSCEPK MVINTVPQLH
SEKTVYLKSS DNRLLMSLLL FIFVLFLCLF SYNCYKGYLP GQCLKFRSAL LLGKKTPKSD
FSDLEQSVKE TLVEPGSFSQ QNGDHPKPAL DTGYETEQDT ITSKVPTDRE DSQRIDELSA
RDKPFDVKCE LKFADSDADG D
