SEM4C_MOUSE
ID SEM4C_MOUSE Reviewed; 834 AA.
AC Q64151;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Semaphorin-4C;
DE AltName: Full=M-Sema F;
DE AltName: Full=Semaphorin-C-like 1;
DE Short=Sema I;
DE Short=Semaphorin I;
DE Flags: Precursor;
GN Name=Sema4c; Synonyms=S4c, Semacl1, Semai;
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 TISSUE=Neonatal brain;
RX PubMed=7656991; DOI=10.1016/0014-5793(95)00850-9;
RA Inagaki S., Furuyama T., Iwahashi Y.;
RT "Identification of a member of mouse semaphorin family.";
RL FEBS Lett. 370:269-272(1995).
RN [2]
RP INTERACTION WITH GIPC.
RX PubMed=10318831; DOI=10.1074/jbc.274.20.14137;
RA Wang L.-H., Kalb R.G., Strittmatter S.M.;
RT "A PDZ protein regulates the distribution of the transmembrane semaphorin,
RT M-SemF.";
RL J. Biol. Chem. 274:14137-14146(1999).
RN [3]
RP INTERACTION WITH NCDN.
RX PubMed=11162505; DOI=10.1006/bbrc.2000.4080;
RA Ohoka Y., Hirotani M., Sugimoto H., Fujioka S., Furuyama T., Inagaki S.;
RT "Semaphorin 4C, a transmembrane semaphorin, associates with a neurite-
RT outgrowth-related protein, SFAP75.";
RL Biochem. Biophys. Res. Commun. 280:237-243(2001).
RN [4]
RP SUBCELLULAR LOCATION, INTERACTION WITH DLG4, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND MUTAGENESIS OF SER-832; SER-833 AND VAL-834.
RX PubMed=11134026; DOI=10.1074/jbc.m009051200;
RA Inagaki S., Ohoka Y., Sugimoto H., Fujioka S., Amazaki M., Kurinami H.,
RA Miyazaki N., Tohyama M., Furuyama T.;
RT "Sema4c, a transmembrane semaphorin, interacts with a post-synaptic density
RT protein, PSD-95.";
RL J. Biol. Chem. 276:9174-9181(2001).
RN [5]
RP FUNCTION, MUTAGENESIS OF SER-832 AND VAL-834, AND INDUCTION.
RX PubMed=15811348; DOI=10.1016/j.febslet.2005.03.022;
RA Ko J.-A., Gondo T., Inagaki S., Inui M.;
RT "Requirement of the transmembrane semaphorin Sema4C for myogenic
RT differentiation.";
RL FEBS Lett. 579:2236-2242(2005).
RN [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=17498836; DOI=10.1016/j.ejcb.2007.03.002;
RA Wu H., Wang X., Liu S., Wu Y., Zhao T., Chen X., Zhu L., Wu Y., Ding X.,
RA Peng X., Yuan J., Wang X., Fan W., Fan M.;
RT "Sema4C participates in myogenic differentiation in vivo and in vitro
RT through the p38 MAPK pathway.";
RL Eur. J. Cell Biol. 86:331-344(2007).
RN [7]
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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 [9]
RP FUNCTION, INTERACTION WITH PLXNB2, AND DISRUPTION PHENOTYPE.
RX PubMed=21122816; DOI=10.1016/j.mcn.2010.11.005;
RA Maier V., Jolicoeur C., Rayburn H., Takegahara N., Kumanogoh A.,
RA Kikutani H., Tessier-Lavigne M., Wurst W., Friedel R.H.;
RT "Semaphorin 4C and 4G are ligands of Plexin-B2 required in cerebellar
RT development.";
RL Mol. Cell. Neurosci. 46:419-431(2011).
CC -!- FUNCTION: Cell surface receptor for PLXNB2 that plays an important role
CC in cell-cell signaling. PLXNB2 binding promotes downstream activation
CC of RHOA and phosphorylation of ERBB2 at 'Tyr-1248'. Required for normal
CC brain development, axon guidance and cell migration. Probable signaling
CC receptor which may play a role in myogenic differentiation through
CC activation of the stress-activated MAPK cascade.
CC {ECO:0000269|PubMed:15811348, ECO:0000269|PubMed:17498836,
CC ECO:0000269|PubMed:17554007, ECO:0000269|PubMed:21122816}.
CC -!- SUBUNIT: Interacts (via the PDZ-binding motif) with GIPC (via the PDZ
CC domain). Interacts with NCDN. Interacts (via the PDZ-binding motif)
CC with DLG4. Interacts with PLXNB2. {ECO:0000269|PubMed:10318831,
CC ECO:0000269|PubMed:11134026, ECO:0000269|PubMed:11162505,
CC ECO:0000269|PubMed:17554007, ECO:0000269|PubMed:21122816}.
CC -!- INTERACTION:
CC Q64151; Q9Z0G0: Gipc1; NbExp=8; IntAct=EBI-987075, EBI-300855;
CC Q64151; Q9Z2H7: Gipc2; NbExp=3; IntAct=EBI-987075, EBI-987119;
CC -!- SUBCELLULAR LOCATION: Postsynaptic density membrane
CC {ECO:0000269|PubMed:11134026}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:11134026}. Cytoplasmic vesicle, secretory vesicle,
CC synaptic vesicle membrane {ECO:0000269|PubMed:11134026}; Single-pass
CC type I membrane protein {ECO:0000269|PubMed:11134026}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain (at protein
CC level). {ECO:0000269|PubMed:11134026}.
CC -!- DEVELOPMENTAL STAGE: First detected at 14 dpc, levels increase by birth
CC and remain strong in the adult brain (at protein level). Expressed
CC widely in the nervous tissues during development.
CC {ECO:0000269|PubMed:11134026}.
CC -!- INDUCTION: Up-regulated in differentiating myoblasts and upon muscle
CC regeneration (at protein level). {ECO:0000269|PubMed:15811348,
CC ECO:0000269|PubMed:17498836}.
CC -!- DISRUPTION PHENOTYPE: Partial neonate lethality, due to defects in
CC brain and neural tube development. In about one third of the embryos
CC cranial neural folds fail to converge, leading to an open neural tube
CC and exencephaly. Mice without exencephaly are viable and fertile.
CC {ECO:0000269|PubMed:21122816}.
CC -!- SIMILARITY: Belongs to the semaphorin family. {ECO:0000305}.
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DR EMBL; S79463; AAB35184.1; -; mRNA.
DR CCDS; CCDS48240.1; -.
DR PIR; S66498; S66498.
DR RefSeq; NP_001119519.1; NM_001126047.3.
DR RefSeq; NP_001291258.1; NM_001304329.1.
DR RefSeq; NP_001291259.1; NM_001304330.1.
DR RefSeq; XP_006495868.1; XM_006495805.2.
DR RefSeq; XP_006495870.1; XM_006495807.1.
DR RefSeq; XP_006495871.1; XM_006495808.2.
DR RefSeq; XP_006495872.1; XM_006495809.3.
DR RefSeq; XP_006495873.1; XM_006495810.3.
DR AlphaFoldDB; Q64151; -.
DR SMR; Q64151; -.
DR BioGRID; 203168; 5.
DR IntAct; Q64151; 2.
DR MINT; Q64151; -.
DR STRING; 10090.ENSMUSP00000110643; -.
DR GlyGen; Q64151; 6 sites.
DR iPTMnet; Q64151; -.
DR PhosphoSitePlus; Q64151; -.
DR EPD; Q64151; -.
DR MaxQB; Q64151; -.
DR PaxDb; Q64151; -.
DR PeptideAtlas; Q64151; -.
DR PRIDE; Q64151; -.
DR ProteomicsDB; 261152; -.
DR Antibodypedia; 2594; 188 antibodies from 30 providers.
DR Ensembl; ENSMUST00000114991; ENSMUSP00000110643; ENSMUSG00000026121.
DR Ensembl; ENSMUST00000191642; ENSMUSP00000142284; ENSMUSG00000026121.
DR Ensembl; ENSMUST00000191677; ENSMUSP00000141263; ENSMUSG00000026121.
DR Ensembl; ENSMUST00000195620; ENSMUSP00000141527; ENSMUSG00000026121.
DR GeneID; 20353; -.
DR KEGG; mmu:20353; -.
DR UCSC; uc007aqq.4; mouse.
DR CTD; 54910; -.
DR MGI; MGI:109252; Sema4c.
DR VEuPathDB; HostDB:ENSMUSG00000026121; -.
DR eggNOG; KOG3611; Eukaryota.
DR GeneTree; ENSGT00940000159885; -.
DR HOGENOM; CLU_009051_4_2_1; -.
DR InParanoid; Q64151; -.
DR OMA; CSAPNWQ; -.
DR OrthoDB; 176445at2759; -.
DR PhylomeDB; Q64151; -.
DR TreeFam; TF316102; -.
DR BioGRID-ORCS; 20353; 0 hits in 59 CRISPR screens.
DR ChiTaRS; Sema4c; mouse.
DR PRO; PR:Q64151; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q64151; protein.
DR Bgee; ENSMUSG00000026121; Expressed in ectoplacental cone and 196 other tissues.
DR ExpressionAtlas; Q64151; baseline and differential.
DR Genevisible; Q64151; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0045499; F:chemorepellent activity; IBA:GO_Central.
DR GO; GO:0030215; F:semaphorin receptor binding; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0021535; P:cell migration in hindbrain; IMP:UniProtKB.
DR GO; GO:0021549; P:cerebellum development; IMP:UniProtKB.
DR GO; GO:0042692; P:muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:0050919; P:negative chemotaxis; IBA:GO_Central.
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:0001843; P:neural tube closure; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; ISS:UniProtKB.
DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; IMP:UniProtKB.
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; IPR003599; Ig_sub.
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; SM00409; IG; 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; Cytoplasmic vesicle; Developmental protein; Differentiation;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
KW Neurogenesis; Phosphoprotein; Postsynaptic cell membrane;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..834
FT /note="Semaphorin-4C"
FT /id="PRO_0000032326"
FT TOPO_DOM 21..664
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 665..685
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 686..834
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..497
FT /note="Sema"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DOMAIN 499..552
FT /note="PSI"
FT DOMAIN 557..645
FT /note="Ig-like C2-type"
FT REGION 46..489
FT /note="Dominant negative effect on myogenic
FT differentiation"
FT REGION 749..834
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 831..834
FT /note="PDZ-binding"
FT COMPBIAS 755..771
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 805..820
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 743
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9C0C4"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 419
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 522
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 565
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 99..110
FT /evidence="ECO:0000250"
FT DISULFID 128..137
FT /evidence="ECO:0000250"
FT DISULFID 261..370
FT /evidence="ECO:0000250"
FT DISULFID 285..330
FT /evidence="ECO:0000250"
FT DISULFID 500..517
FT /evidence="ECO:0000250"
FT DISULFID 509..526
FT /evidence="ECO:0000250"
FT DISULFID 578..628
FT /evidence="ECO:0000250"
FT MUTAGEN 832
FT /note="S->A: Loss of the effect on myogenic
FT differentiation; when associated with A-834. Loss of
FT interaction with DLG4; when associated with A-833 and A-
FT 834."
FT /evidence="ECO:0000269|PubMed:11134026,
FT ECO:0000269|PubMed:15811348"
FT MUTAGEN 833
FT /note="S->A: Loss of interaction with DLG4; when associated
FT with A-832 and A-834."
FT /evidence="ECO:0000269|PubMed:11134026"
FT MUTAGEN 834
FT /note="V->A: Loss of the effect on myogenic
FT differentiation; when associated with A-832. Loss of
FT interaction with DLG4; when associated with A-832 and A-
FT 833."
FT /evidence="ECO:0000269|PubMed:11134026,
FT ECO:0000269|PubMed:15811348"
SQ SEQUENCE 834 AA; 92557 MW; 6868BB5BF571482D CRC64;
MAPHWAVWLL AAGLWGLGIG AEMWWNLVPR KTVSSGELVT VVRRFSQTGI QDFLTLTLTE
HSGLLYVGAR EALFAFSVEA LELQGAISWE APAEKKIECT QKGKSNQTEC FNFIRFLQPY
NSSHLYVCGT YAFQPKCTYI NMLTFTLDRA EFEDGKGKCP YDPAKGHTGL LVDGELYSAT
LNNFLGTEPV ILRYMGTHHS IKTEYLAFWL NEPHFVGSAF VPESVGSFTG DDDKIYFFFS
ERAVEYDCYS EQVVARVARV CKGDMGGART LQKKWTTFLK ARLVCSAPDW KVYFNQLKAV
HTLRGASWHN TTFFGVFQAR WGDMDLSAVC EYQLEQIQQV FEGPYKEYSE QAQKWARYTD
PVPSPRPGSC INNWHRDNGY TSSLELPDNT LNFIKKHPLM EDQVKPRLGR PLLVKKNTNF
THVVADRVPG LDGATYTVLF IGTGDGWLLK AVSLGPWIHM VEELQVFDQE PVESLVLSQS
KKVLFAGSRS QLVQLSLADC TKYRFCVDCV LARDPYCAWN VNTSRCVATT SGRSGSFLVQ
HVANLDTSKM CNQYGIKKVR SIPKNITVVS GTDLVLPCHL SSNLAHAHWT FGSQDLPAEQ
PGSFLYDTGL QALVVMAAQS RHSGPYRCYS EEQGTRLAAE SYLVAVVAGS SVTLEARAPL
ENLGLVWLAV VALGAVCLVL LLLVLSLRRR LREELEKGAK ASERTLVYPL ELPKEPASPP
FRPGPETDEK LWDPVGYYYS DGSLKIVPGH ARCQPGGGPP SPPPGIPGQP LPSPTRLHLG
GGRNSNANGY VRLQLGGEDR GGSGHPLPEL ADELRRKLQQ RQPLPDSNPE ESSV
