GSDMC_HUMAN
ID GSDMC_HUMAN Reviewed; 508 AA.
AC Q9BYG8; Q5XKF3; Q6P494;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Gasdermin-C {ECO:0000303|PubMed:17350798};
DE AltName: Full=Melanoma-derived leucine zipper-containing extranuclear factor {ECO:0000303|PubMed:11223543};
DE Contains:
DE RecName: Full=Gasdermin-C, N-terminal {ECO:0000305};
DE Short=GSDMC-NT {ECO:0000305};
DE Contains:
DE RecName: Full=Gasdermin-C, C-terminal {ECO:0000305};
DE Short=GSDMC-CT {ECO:0000305};
GN Name=GSDMC {ECO:0000303|PubMed:17350798, ECO:0000312|HGNC:HGNC:7151};
GN Synonyms=MLZE {ECO:0000303|PubMed:11223543};
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 [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Cervix;
RX PubMed=11223543; DOI=10.1111/j.1349-7006.2001.tb01076.x;
RA Watabe K., Ito A., Asada H., Endo Y., Kobayashi T., Nakamoto K., Itami S.,
RA Takao S., Shinomura Y., Aikou T., Yoshikawa K., Matsuzawa Y., Kitamura Y.,
RA Nojima H.;
RT "Structure, expression and chromosome mapping of MLZE, a novel gene which
RT is preferentially expressed in metastatic melanoma cells.";
RL Jpn. J. Cancer Res. 92:140-151(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS SER-23 AND THR-475.
RC TISSUE=Skin;
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 IDENTIFICATION.
RX PubMed=17350798; DOI=10.1016/j.ygeno.2007.01.003;
RA Tamura M., Tanaka S., Fujii T., Aoki A., Komiyama H., Ezawa K.,
RA Sumiyama K., Sagai T., Shiroishi T.;
RT "Members of a novel gene family, Gsdm, are expressed exclusively in the
RT epithelium of the skin and gastrointestinal tract in a highly tissue-
RT specific manner.";
RL Genomics 89:618-629(2007).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=19051310; DOI=10.1002/gcc.20636;
RA Saeki N., Usui T., Aoyagi K., Kim D.H., Sato M., Mabuchi T., Yanagihara K.,
RA Ogawa K., Sakamoto H., Yoshida T., Sasaki H.;
RT "Distinctive expression and function of four GSDM family genes (GSDMA-D) in
RT normal and malignant upper gastrointestinal epithelium.";
RL Genes Chromosomes Cancer 48:261-271(2009).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF LEU-319; TYR-398 AND ALA-402.
RX PubMed=27281216; DOI=10.1038/nature18590;
RA Ding J., Wang K., Liu W., She Y., Sun Q., Shi J., Sun H., Wang D.C.,
RA Shao F.;
RT "Pore-forming activity and structural autoinhibition of the gasdermin
RT family.";
RL Nature 535:111-116(2016).
CC -!- FUNCTION: [Gasdermin-C]: This form constitutes the precursor of the
CC pore-forming protein: upon cleavage, the released N-terminal moiety
CC (Gasdermin-C, N-terminal) binds to membranes and forms pores,
CC triggering cell death. {ECO:0000250|UniProtKB:Q96QA5}.
CC -!- FUNCTION: [Gasdermin-C, N-terminal]: Pore-forming protein that causes
CC membrane permeabilization and pyroptosis (PubMed:27281216). Released
CC upon cleavage and binds to membrane inner leaflet lipids.
CC Homooligomerizes within the membrane and forms pores of 10-15
CC nanometers (nm) of inner diameter, triggering pyroptosis (By
CC similarity). The functional mechanisms and physiological proteases that
CC cleave and activate this pore-forming protein are unknown (Probable).
CC {ECO:0000250|UniProtKB:Q96QA5, ECO:0000269|PubMed:27281216,
CC ECO:0000305}.
CC -!- ACTIVITY REGULATION: [Gasdermin-C]: The full-length protein before
CC cleavage is inactive: intramolecular interactions between N- and C-
CC terminal domains mediate autoinhibition in the absence of activation
CC signal. The intrinsic pyroptosis-inducing activity is carried by the
CC released N-terminal moiety (Gasdermin-C, N-terminal).
CC {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- SUBUNIT: [Gasdermin-C, N-terminal]: Homooligomer; homooligomeric ring-
CC shaped pore complex containing 27-28 subunits when inserted in the
CC membrane. {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-C]: Cytoplasm, cytosol
CC {ECO:0000269|PubMed:11223543}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-C, N-terminal]: Cell membrane
CC {ECO:0000250|UniProtKB:Q5Y4Y6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- TISSUE SPECIFICITY: Expressed mainly in trachea and spleen
CC (PubMed:11223543). In the esophagus, expressed in differentiating cells
CC and probably in differentiated cells. Also detected in gastric
CC epithelium (PubMed:19051310). {ECO:0000269|PubMed:11223543,
CC ECO:0000269|PubMed:19051310}.
CC -!- DOMAIN: Intramolecular interactions between N- and C-terminal domains
CC are important for autoinhibition in the absence of activation signal
CC (By similarity). The intrinsic pyroptosis-inducing activity is carried
CC by the N-terminal domain (By similarity).
CC {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- PTM: Cleavage relieves autoinhibition by releasing the N-terminal
CC moiety (Gasdermin-C, N-terminal) that initiates pyroptosis.
CC {ECO:0000250|UniProtKB:P57764}.
CC -!- SIMILARITY: Belongs to the gasdermin family. {ECO:0000305}.
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DR EMBL; AB042405; BAB40331.1; -; mRNA.
DR EMBL; AC022849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035321; AAH35321.1; -; mRNA.
DR EMBL; BC063595; AAH63595.1; -; mRNA.
DR CCDS; CCDS6360.1; -.
DR RefSeq; NP_113603.1; NM_031415.2.
DR AlphaFoldDB; Q9BYG8; -.
DR SMR; Q9BYG8; -.
DR BioGRID; 121101; 6.
DR STRING; 9606.ENSP00000276708; -.
DR TCDB; 1.C.123.1.4; the pore-forming gasdermin (gasdermin) family.
DR iPTMnet; Q9BYG8; -.
DR PhosphoSitePlus; Q9BYG8; -.
DR BioMuta; GSDMC; -.
DR DMDM; 311033444; -.
DR EPD; Q9BYG8; -.
DR MassIVE; Q9BYG8; -.
DR PaxDb; Q9BYG8; -.
DR PeptideAtlas; Q9BYG8; -.
DR PRIDE; Q9BYG8; -.
DR ProteomicsDB; 79642; -.
DR Antibodypedia; 14017; 168 antibodies from 27 providers.
DR DNASU; 56169; -.
DR Ensembl; ENST00000276708.9; ENSP00000276708.4; ENSG00000147697.9.
DR Ensembl; ENST00000619643.1; ENSP00000482343.1; ENSG00000147697.9.
DR GeneID; 56169; -.
DR KEGG; hsa:56169; -.
DR MANE-Select; ENST00000276708.9; ENSP00000276708.4; NM_031415.3; NP_113603.1.
DR UCSC; uc003ysr.3; human.
DR CTD; 56169; -.
DR DisGeNET; 56169; -.
DR GeneCards; GSDMC; -.
DR HGNC; HGNC:7151; GSDMC.
DR HPA; ENSG00000147697; Tissue enhanced (esophagus, lymphoid tissue, skin, vagina).
DR MIM; 608384; gene.
DR neXtProt; NX_Q9BYG8; -.
DR OpenTargets; ENSG00000147697; -.
DR PharmGKB; PA162390324; -.
DR VEuPathDB; HostDB:ENSG00000147697; -.
DR eggNOG; ENOG502S0IQ; Eukaryota.
DR GeneTree; ENSGT00950000183140; -.
DR HOGENOM; CLU_040752_2_0_1; -.
DR InParanoid; Q9BYG8; -.
DR OMA; ISLWITY; -.
DR OrthoDB; 1067854at2759; -.
DR PhylomeDB; Q9BYG8; -.
DR TreeFam; TF331886; -.
DR PathwayCommons; Q9BYG8; -.
DR BioGRID-ORCS; 56169; 19 hits in 1069 CRISPR screens.
DR ChiTaRS; GSDMC; human.
DR GenomeRNAi; 56169; -.
DR Pharos; Q9BYG8; Tbio.
DR PRO; PR:Q9BYG8; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9BYG8; protein.
DR Bgee; ENSG00000147697; Expressed in lower esophagus mucosa and 87 other tissues.
DR Genevisible; Q9BYG8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IBA:GO_Central.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IBA:GO_Central.
DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central.
DR GO; GO:0070269; P:pyroptosis; IBA:GO_Central.
DR InterPro; IPR007677; Gasdermin.
DR InterPro; IPR040460; Gasdermin_pore.
DR InterPro; IPR041263; Gasdermin_PUB.
DR PANTHER; PTHR16399; PTHR16399; 1.
DR Pfam; PF04598; Gasdermin; 1.
DR Pfam; PF17708; Gasdermin_C; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Membrane; Necrosis; Reference proteome;
KW Transmembrane; Transmembrane beta strand.
FT CHAIN 1..508
FT /note="Gasdermin-C"
FT /id="PRO_0000148180"
FT CHAIN 1..?
FT /note="Gasdermin-C, N-terminal"
FT /evidence="ECO:0000305"
FT /id="PRO_0000451674"
FT CHAIN ?..508
FT /note="Gasdermin-C, C-terminal"
FT /evidence="ECO:0000305"
FT /id="PRO_0000451675"
FT REGION 1..257
FT /note="Triggers pyroptosis"
FT /evidence="ECO:0000269|PubMed:27281216"
FT VARIANT 23
FT /note="P -> S (in dbSNP:rs10090835)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_028138"
FT VARIANT 150
FT /note="R -> K (in dbSNP:rs16904151)"
FT /id="VAR_028139"
FT VARIANT 475
FT /note="M -> T (in dbSNP:rs4144738)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_028140"
FT MUTAGEN 319
FT /note="L->D: Low spontaneous pyroptosis-inducing activity."
FT /evidence="ECO:0000269|PubMed:27281216"
FT MUTAGEN 398
FT /note="Y->D: Low spontaneous pyroptosis-inducing activity."
FT /evidence="ECO:0000269|PubMed:27281216"
FT MUTAGEN 402
FT /note="A->D: Spontaneous pyroptosis-inducing activity."
FT /evidence="ECO:0000269|PubMed:27281216"
SQ SEQUENCE 508 AA; 57692 MW; 9CB6054AFA1ED88C CRC64;
MPSMLERISK NLVKEIGSKD LTPVKYLLSA TKLRQFVILR KKKDSRSSFW EQSDYVPVEF
SLNDILEPSS SVLETVVTGP FHFSDIMIQK HKADMGVNVG IEVSVSGEAS VDHGCSLEFQ
IVTIPSPNLE DFQKRKLLDP EPSFLKECRR RGDNLYVVTE AVELINNTVL YDSSSVNILG
KIALWITYGK GQGQGESLRV KKKALTLQKG MVMAYKRKQL VIKEKAILIS DDDEQRTFQD
EYEISEMVGY CAARSEGLLP SFHTISPTLF NASSNDMKLK PELFLTQQFL SGHLPKYEQV
HILPVGRIEE PFWQNFKHLQ EEVFQKIKTL AQLSKDVQDV MFYSILAMLR DRGALQDLMN
MLELDSSGHL DGPGGAILKK LQQDSNHAWF NPKDPILYLL EAIMVLSDFQ HDLLACSMEK
RILLQQQELV RSILEPNFRY PWSIPFTLKP ELLAPLQSEG LAITYGLLEE CGLRMELDNP
RSTWDVEAKM PLSALYGTLS LLQQLAEA
