SEM4C_HUMAN
ID SEM4C_HUMAN Reviewed; 833 AA.
AC Q9C0C4; Q32MJ3; Q7Z5X0;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Semaphorin-4C;
DE Flags: Precursor;
GN Name=SEMA4C; Synonyms=KIAA1739, SEMAI; ORFNames=UNQ5855/PRO34487;
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 [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 37-833.
RC TISSUE=Brain;
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [4]
RP FUNCTION.
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-742, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP IDENTIFICATION BY 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 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 (By similarity).
CC Probable signaling receptor which may play a role in myogenic
CC differentiation through activation of the stress-activated MAPK
CC cascade. {ECO:0000250, ECO:0000269|PubMed:17498836}.
CC -!- SUBUNIT: Interacts (via the PDZ-binding motif) with GIPC (via the PDZ
CC domain) (By similarity). Interacts with NCDN (By similarity). Interacts
CC (via the PDZ-binding motif) with DLG4. Interacts with PLXNB2 (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9C0C4; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-10303490, EBI-3867333;
CC Q9C0C4; O75031: HSF2BP; NbExp=3; IntAct=EBI-10303490, EBI-7116203;
CC Q9C0C4; P08779: KRT16; NbExp=3; IntAct=EBI-10303490, EBI-356410;
CC Q9C0C4; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-10303490, EBI-3044087;
CC Q9C0C4; Q15323: KRT31; NbExp=6; IntAct=EBI-10303490, EBI-948001;
CC Q9C0C4; O76011: KRT34; NbExp=3; IntAct=EBI-10303490, EBI-1047093;
CC Q9C0C4; Q6A162: KRT40; NbExp=3; IntAct=EBI-10303490, EBI-10171697;
CC Q9C0C4; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-10303490, EBI-945833;
CC Q9C0C4; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-10303490, EBI-22310682;
CC Q9C0C4; O43933: PEX1; NbExp=3; IntAct=EBI-10303490, EBI-988601;
CC Q9C0C4; Q8ND90: PNMA1; NbExp=6; IntAct=EBI-10303490, EBI-302345;
CC Q9C0C4; Q96PM5: RCHY1; NbExp=3; IntAct=EBI-10303490, EBI-947779;
CC Q9C0C4; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-10303490, EBI-739895;
CC Q9C0C4; O76024: WFS1; NbExp=3; IntAct=EBI-10303490, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Postsynaptic density membrane {ECO:0000250};
CC Single-pass type I membrane protein {ECO:0000250}. Cytoplasmic vesicle,
CC secretory vesicle, synaptic vesicle membrane {ECO:0000250}; Single-pass
CC type I membrane protein {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the semaphorin family. {ECO:0000305}.
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DR EMBL; AY358842; AAQ89201.1; -; mRNA.
DR EMBL; BC017476; AAH17476.2; -; mRNA.
DR EMBL; BC109103; AAI09104.1; -; mRNA.
DR EMBL; BC109104; AAI09105.1; -; mRNA.
DR EMBL; AB051526; BAB21830.1; -; mRNA.
DR CCDS; CCDS2029.1; -.
DR RefSeq; NP_060259.4; NM_017789.4.
DR RefSeq; XP_011509680.1; XM_011511378.2.
DR RefSeq; XP_011509681.1; XM_011511379.2.
DR RefSeq; XP_011509682.1; XM_011511380.1.
DR RefSeq; XP_011509683.1; XM_011511381.1.
DR RefSeq; XP_011509684.1; XM_011511382.2.
DR RefSeq; XP_011509685.1; XM_011511383.1.
DR PDB; 6N5Z; X-ray; 2.45 A; A/B=731-755.
DR PDBsum; 6N5Z; -.
DR AlphaFoldDB; Q9C0C4; -.
DR SMR; Q9C0C4; -.
DR BioGRID; 120254; 171.
DR IntAct; Q9C0C4; 27.
DR MINT; Q9C0C4; -.
DR STRING; 9606.ENSP00000306844; -.
DR GlyConnect; 1733; 3 N-Linked glycans (1 site).
DR GlyGen; Q9C0C4; 7 sites, 3 N-linked glycans (1 site).
DR iPTMnet; Q9C0C4; -.
DR PhosphoSitePlus; Q9C0C4; -.
DR BioMuta; SEMA4C; -.
DR DMDM; 47606208; -.
DR EPD; Q9C0C4; -.
DR jPOST; Q9C0C4; -.
DR MassIVE; Q9C0C4; -.
DR MaxQB; Q9C0C4; -.
DR PaxDb; Q9C0C4; -.
DR PeptideAtlas; Q9C0C4; -.
DR PRIDE; Q9C0C4; -.
DR ProteomicsDB; 79997; -.
DR Antibodypedia; 2594; 188 antibodies from 30 providers.
DR DNASU; 54910; -.
DR Ensembl; ENST00000305476.10; ENSP00000306844.5; ENSG00000168758.11.
DR GeneID; 54910; -.
DR KEGG; hsa:54910; -.
DR MANE-Select; ENST00000305476.10; ENSP00000306844.5; NM_017789.5; NP_060259.4.
DR UCSC; uc002sxh.5; human.
DR CTD; 54910; -.
DR DisGeNET; 54910; -.
DR GeneCards; SEMA4C; -.
DR HGNC; HGNC:10731; SEMA4C.
DR HPA; ENSG00000168758; Low tissue specificity.
DR MIM; 604462; gene.
DR neXtProt; NX_Q9C0C4; -.
DR OpenTargets; ENSG00000168758; -.
DR PharmGKB; PA35653; -.
DR VEuPathDB; HostDB:ENSG00000168758; -.
DR eggNOG; KOG3611; Eukaryota.
DR GeneTree; ENSGT00940000159885; -.
DR HOGENOM; CLU_009051_4_2_1; -.
DR InParanoid; Q9C0C4; -.
DR OMA; CSAPNWQ; -.
DR OrthoDB; 176445at2759; -.
DR PhylomeDB; Q9C0C4; -.
DR TreeFam; TF316102; -.
DR PathwayCommons; Q9C0C4; -.
DR SignaLink; Q9C0C4; -.
DR BioGRID-ORCS; 54910; 12 hits in 1078 CRISPR screens.
DR GeneWiki; SEMA4C; -.
DR GenomeRNAi; 54910; -.
DR Pharos; Q9C0C4; Tbio.
DR PRO; PR:Q9C0C4; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9C0C4; protein.
DR Bgee; ENSG00000168758; Expressed in olfactory bulb and 205 other tissues.
DR ExpressionAtlas; Q9C0C4; baseline and differential.
DR Genevisible; Q9C0C4; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030672; C:synaptic vesicle membrane; ISS: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; ISS:UniProtKB.
DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR GO; GO:0042692; P:muscle cell differentiation; IDA: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; ISS: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; IDA:UniProtKB.
DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; ISS: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 3D-structure; Cell membrane; Cytoplasmic vesicle; Developmental protein;
KW Differentiation; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Membrane; Neurogenesis; Phosphoprotein; Postsynaptic cell membrane;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..833
FT /note="Semaphorin-4C"
FT /id="PRO_0000032325"
FT TOPO_DOM 21..663
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 664..684
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 685..833
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..497
FT /note="Sema"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DOMAIN 499..551
FT /note="PSI"
FT DOMAIN 556..644
FT /note="Ig-like C2-type"
FT REGION 46..489
FT /note="Dominant negative effect on myogenic
FT differentiation"
FT /evidence="ECO:0000250"
FT REGION 748..807
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 814..833
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 830..833
FT /note="PDZ-binding"
FT COMPBIAS 754..770
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 742
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
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 564
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 CONFLICT 602
FT /note="S -> T (in Ref. 1; AAQ89201)"
FT /evidence="ECO:0000305"
FT STRAND 735..739
FT /evidence="ECO:0007829|PDB:6N5Z"
FT STRAND 742..745
FT /evidence="ECO:0007829|PDB:6N5Z"
SQ SEQUENCE 833 AA; 92623 MW; 075FDC0A392F0CE3 CRC64;
MAPHWAVWLL AARLWGLGIG AEVWWNLVPR KTVSSGELAT VVRRFSQTGI QDFLTLTLTE
PTGLLYVGAR EALFAFSMEA LELQGAISWE APVEKKTECI QKGKNNQTEC FNFIRFLQPY
NASHLYVCGT YAFQPKCTYV NMLTFTLEHG EFEDGKGKCP YDPAKGHAGL LVDGELYSAT
LNNFLGTEPI ILRNMGPHHS MKTEYLAFWL NEPHFVGSAY VPESVGSFTG DDDKVYFFFR
ERAVESDCYA EQVVARVARV CKGDMGGART LQRKWTTFLK ARLACSAPNW QLYFNQLQAM
HTLQDTSWHN TTFFGVFQAQ WGDMYLSAIC EYQLEEIQRV FEGPYKEYHE EAQKWDRYTD
PVPSPRPGSC INNWHRRHGY TSSLELPDNI LNFVKKHPLM EEQVGPRWSR PLLVKKGTNF
THLVADRVTG LDGATYTVLF IGTGDGWLLK AVSLGPWVHL IEELQLFDQE PMRSLVLSQS
KKLLFAGSRS QLVQLPVADC MKYRSCADCV LARDPYCAWS VNTSRCVAVG GHSGSLLIQH
VMTSDTSGIC NLRGSKKVRP TPKNITVVAG TDLVLPCHLS SNLAHARWTF GGRDLPAEQP
GSFLYDARLQ ALVVMAAQPR HAGAYHCFSE EQGARLAAEG YLVAVVAGPS VTLEARAPLE
NLGLVWLAVV ALGAVCLVLL LLVLSLRRRL REELEKGAKA TERTLVYPLE LPKEPTSPPF
RPCPEPDEKL WDPVGYYYSD GSLKIVPGHA RCQPGGGPPS PPPGIPGQPL PSPTRLHLGG
GRNSNANGYV RLQLGGEDRG GLGHPLPELA DELRRKLQQR QPLPDSNPEE SSV
