GSDMB_HUMAN
ID GSDMB_HUMAN Reviewed; 416 AA.
AC Q8TAX9; B4DKK7; Q7Z377; Q8WY76; Q9NX71; Q9P163;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Gasdermin-B {ECO:0000305};
DE AltName: Full=Gasdermin-like protein {ECO:0000303|PubMed:16625320};
DE Contains:
DE RecName: Full=Gasdermin-B, N-terminal {ECO:0000305};
DE Short=GSDMB-NT {ECO:0000305};
DE Short=p30 {ECO:0000303|PubMed:32299851};
DE Contains:
DE RecName: Full=Gasdermin-B, C-terminal {ECO:0000305};
DE Short=GSDMB-CT {ECO:0000305};
DE Short=p16 {ECO:0000303|PubMed:32299851};
GN Name=GSDMB {ECO:0000303|PubMed:27281216, ECO:0000312|HGNC:HGNC:23690};
GN Synonyms=GSDML {ECO:0000303|PubMed:16625320};
GN ORFNames=PP4052 {ECO:0000303|PubMed:15498874},
GN PRO2521 {ECO:0000303|PubMed:11483580};
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] (ISOFORM 2).
RC TISSUE=Fetal liver;
RX PubMed=11483580; DOI=10.1101/gr.175501;
RA Yu Y., Zhang C., Zhou G., Wu S., Qu X., Wei H., Xing G., Dong C., Zhai Y.,
RA Wan J., Ouyang S., Li L., Zhang S., Zhou K., Zhang Y., Wu C., He F.;
RT "Gene expression profiling in human fetal liver and identification of
RT tissue- and developmental-stage-specific genes through compiled expression
RT profiles and efficient cloning of full-length cDNAs.";
RL Genome Res. 11:1392-1403(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 6), AND VARIANTS
RP ARG-304 AND SER-311.
RC TISSUE=Colon;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ARG-304
RP AND SER-311.
RC TISSUE=Lung;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 70-411 (ISOFORM 4).
RC TISSUE=Rectum tumor;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, PROTEOLYTIC CLEAVAGE, INDUCTION, AND
RP MUTAGENESIS OF LYS-229 AND LYS-244.
RX PubMed=32299851; DOI=10.1126/science.aaz7548;
RA Zhou Z., He H., Wang K., Shi X., Wang Y., Su Y., Wang Y., Li D., Liu W.,
RA Zhang Y., Shen L., Han W., Shen L., Ding J., Shao F.;
RT "Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis
RT in target cells.";
RL Science 368:0-0(2020).
RN [9]
RP ALTERNATIVE PROMOTER USAGE.
RX PubMed=16625320; DOI=10.1007/s00705-006-0764-5;
RA Sin H.-S., Huh J.-W., Kim D.-S., Kang D.W., Min D.S., Kim T.-H., Ha H.-S.,
RA Kim H.-H., Lee S.-Y., Kim H.-S.;
RT "Transcriptional control of the HERV-H LTR element of the GSDML gene in
RT human tissues and cancer cells.";
RL Arch. Virol. 151:1985-1994(2006).
RN [10]
RP MARKER OF CERVICAL LYMPH NODE METASTASIS.
RX PubMed=17391312; DOI=10.1111/j.1349-7006.2007.00454.x;
RA Nguyen S.T., Hasegawa S., Tsuda H., Tomioka H., Ushijima M., Noda M.,
RA Omura K., Miki Y.;
RT "Identification of a predictive gene expression signature of cervical lymph
RT node metastasis in oral squamous cell carcinoma.";
RL Cancer Sci. 98:740-746(2007).
RN [11]
RP GENE FAMILY.
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 [12]
RP ALTERNATIVE SPLICING, AND SUBCELLULAR LOCATION.
RX PubMed=18038310; DOI=10.1080/00313020701716250;
RA Carl-McGrath S., Schneider-Stock R., Ebert M., Roecken C.;
RT "Differential expression and localisation of gasdermin-like (GSDML), a
RT novel member of the cancer-associated GSDMDC protein family, in neoplastic
RT and non-neoplastic gastric, hepatic, and colon tissues.";
RL Pathology 40:13-24(2008).
RN [13]
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 [14]
RP FUNCTION.
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).
RN [15] {ECO:0007744|PDB:5TIB, ECO:0007744|PDB:5TJ2, ECO:0007744|PDB:5TJ4}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 222-413, AND PROTEOLYTIC
RP CLEAVAGE.
RX PubMed=28154144; DOI=10.1073/pnas.1616783114;
RA Chao K.L., Kulakova L., Herzberg O.;
RT "Gene polymorphism linked to increased asthma and IBD risk alters
RT gasdermin-B structure, a sulfatide and phosphoinositide binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E1128-E1137(2017).
RN [16]
RP VARIANT [LARGE SCALE ANALYSIS] GLY-250.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: [Gasdermin-B]: Precursor of a pore-forming protein that acts
CC as a downstream mediator of granzyme-mediated cell death
CC (PubMed:32299851). This form constitutes the precursor of the pore-
CC forming protein: upon cleavage, the released N-terminal moiety
CC (Gasdermin-B, N-terminal) binds to membranes and forms pores,
CC triggering pyroptosis (PubMed:32299851). {ECO:0000269|PubMed:32299851}.
CC -!- FUNCTION: [Gasdermin-B, N-terminal]: Pore-forming protein produced by
CC cleavage by granzyme A (GZMA), which causes membrane permeabilization
CC and pyroptosis in target cells of cytotoxic T and natural killer (NK)
CC cells (PubMed:27281216, PubMed:32299851). Key downstream mediator of
CC granzyme-mediated cell death: (1) granzyme A (GZMA), delivered to
CC target cells from cytotoxic T- and NK-cells, (2) specifically cleaves
CC Gasdermin-B to generate this form (PubMed:32299851). After cleavage,
CC moves to the plasma membrane, homooligomerizes within the membrane and
CC forms pores of 10-15 nanometers (nm) of inner diameter, triggering
CC pyroptosis (PubMed:32299851). Binds to membrane inner leaflet lipids,
CC such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5-
CC phosphate, bisphosphorylated phosphatidylinositols, such as
CC phosphatidylinositol (4,5)-bisphosphate, and more weakly to
CC phosphatidic acid (PubMed:28154144). Also binds sufatide, a component
CC of the apical membrane of epithelial cells (PubMed:28154144).
CC {ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:28154144,
CC ECO:0000269|PubMed:32299851}.
CC -!- ACTIVITY REGULATION: [Gasdermin-B]: 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 (By similarity). The intrinsic pyroptosis-inducing activity is
CC carried by the released N-terminal moiety (Gasdermin-B, N-terminal)
CC following cleavage by granzyme A (GZMA) (PubMed:32299851).
CC {ECO:0000250|UniProtKB:Q5Y4Y6, ECO:0000269|PubMed:32299851}.
CC -!- SUBUNIT: [Gasdermin-B, 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-B]: Cytoplasm
CC {ECO:0000269|PubMed:18038310}. Note=Vesicular localization in the
CC apical region of gastric chief cells and colonic surface mucous cells,
CC and the basal region of neuroendocrine cells.
CC {ECO:0000269|PubMed:18038310}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-B, N-terminal]: Cell membrane
CC {ECO:0000250|UniProtKB:Q5Y4Y6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Comment=Isoforms expression varies between tumor and non-tumor cells
CC and changes in the regulation of isoforms transcription and
CC translation may be seen in the development of gastrointestinal and
CC hepatic cancers.;
CC Name=4;
CC IsoId=Q8TAX9-4; Sequence=Displayed;
CC Name=1;
CC IsoId=Q8TAX9-1; Sequence=VSP_061489, VSP_061490;
CC Name=2;
CC IsoId=Q8TAX9-2; Sequence=VSP_061487;
CC Name=3;
CC IsoId=Q8TAX9-3; Sequence=VSP_061488;
CC Name=5;
CC IsoId=Q8TAX9-5; Sequence=VSP_061486;
CC Name=6;
CC IsoId=Q8TAX9-6; Sequence=VSP_061490;
CC -!- TISSUE SPECIFICITY: In the gastrointestinal tract, expressed in
CC proliferating cells, including in the basal cell layer of esophagus and
CC in isthmus/neck of stomach. {ECO:0000269|PubMed:19051310}.
CC -!- INDUCTION: Expression is induced by interferon-gamma (IFNG).
CC {ECO:0000269|PubMed:32299851}.
CC -!- DOMAIN: Intramolecular interactions between N- and C-terminal domains
CC are important for autoinhibition in the absence of activation signal.
CC The intrinsic pyroptosis-inducing activity is carried by the N-terminal
CC domain. {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- PTM: Cleavage by granzyme A (GZMA) relieves autoinhibition by releasing
CC the N-terminal moiety (Gasdermin-B, N-terminal) that initiates
CC pyroptosis (PubMed:32299851). Not cleaved by other granzymes
CC (PubMed:32299851). Major cleavage site takes places after Lys-244; a
CC minor cleavage site takes place after Lys-229 (PubMed:32299851).
CC {ECO:0000269|PubMed:32299851}.
CC -!- MISCELLANEOUS: Long terminal repeat (LTR) of endogenous retrovirus
CC HERV-H with reverse orientation may serve as alternative promoters of
CC GSDML gene. {ECO:0000269|PubMed:16625320}.
CC -!- MISCELLANEOUS: [Isoform 1]: Non canonical splice junctions.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: GSDML may be used as predictive markers of cervical
CC lymph node metastasis and may help, with a panel of other genes, to
CC discriminate between primary tumors of oral squamous cell carcinoma
CC that metastasize to cervical lymph node and those that do not
CC metastasize. {ECO:0000269|PubMed:17391312}.
CC -!- SIMILARITY: Belongs to the gasdermin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GSDMBID43972ch17q12.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF119884; AAF69638.1; -; mRNA.
DR EMBL; AK000409; BAA91146.1; -; mRNA.
DR EMBL; AK296607; BAG59219.1; -; mRNA.
DR EMBL; AF258572; AAG23775.1; -; mRNA.
DR EMBL; AC090844; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471152; EAW60614.1; -; Genomic_DNA.
DR EMBL; BC025682; AAH25682.1; -; mRNA.
DR EMBL; BX538068; CAD97998.1; -; mRNA.
DR CCDS; CCDS11354.1; -. [Q8TAX9-2]
DR CCDS; CCDS42313.1; -. [Q8TAX9-3]
DR CCDS; CCDS54119.1; -. [Q8TAX9-6]
DR CCDS; CCDS54120.1; -. [Q8TAX9-4]
DR RefSeq; NP_001035936.1; NM_001042471.1. [Q8TAX9-3]
DR RefSeq; NP_001159430.1; NM_001165958.1. [Q8TAX9-4]
DR RefSeq; NP_001159431.1; NM_001165959.1. [Q8TAX9-6]
DR RefSeq; NP_061000.2; NM_018530.2. [Q8TAX9-2]
DR RefSeq; XP_016880339.1; XM_017024850.1.
DR RefSeq; XP_016880340.1; XM_017024851.1.
DR RefSeq; XP_016880341.1; XM_017024852.1.
DR PDB; 5TIB; X-ray; 2.60 A; A/B=251-411.
DR PDB; 5TJ2; X-ray; 2.80 A; A/B/C/D=251-411.
DR PDB; 5TJ4; X-ray; 3.50 A; A/B/C/D/E/F/G/H/I/J=222-413.
DR PDBsum; 5TIB; -.
DR PDBsum; 5TJ2; -.
DR PDBsum; 5TJ4; -.
DR AlphaFoldDB; Q8TAX9; -.
DR SMR; Q8TAX9; -.
DR BioGRID; 120972; 9.
DR IntAct; Q8TAX9; 6.
DR STRING; 9606.ENSP00000415049; -.
DR TCDB; 1.C.123.1.3; the pore-forming gasdermin (gasdermin) family.
DR iPTMnet; Q8TAX9; -.
DR PhosphoSitePlus; Q8TAX9; -.
DR BioMuta; GSDMB; -.
DR DMDM; 182647404; -.
DR jPOST; Q8TAX9; -.
DR MassIVE; Q8TAX9; -.
DR PaxDb; Q8TAX9; -.
DR PeptideAtlas; Q8TAX9; -.
DR PRIDE; Q8TAX9; -.
DR ProteomicsDB; 73934; -. [Q8TAX9-1]
DR ProteomicsDB; 73935; -. [Q8TAX9-2]
DR ProteomicsDB; 73936; -. [Q8TAX9-3]
DR ProteomicsDB; 73937; -. [Q8TAX9-4]
DR ProteomicsDB; 73938; -. [Q8TAX9-5]
DR ProteomicsDB; 73939; -. [Q8TAX9-6]
DR Antibodypedia; 4429; 232 antibodies from 31 providers.
DR DNASU; 55876; -.
DR Ensembl; ENST00000309481.11; ENSP00000312584.7; ENSG00000073605.19. [Q8TAX9-3]
DR Ensembl; ENST00000360317.7; ENSP00000353465.3; ENSG00000073605.19. [Q8TAX9-4]
DR Ensembl; ENST00000394175.6; ENSP00000377729.2; ENSG00000073605.19. [Q8TAX9-2]
DR Ensembl; ENST00000394179.5; ENSP00000377733.2; ENSG00000073605.19. [Q8TAX9-3]
DR Ensembl; ENST00000418519.6; ENSP00000415049.1; ENSG00000073605.19. [Q8TAX9-4]
DR Ensembl; ENST00000520542.5; ENSP00000430157.1; ENSG00000073605.19. [Q8TAX9-6]
DR GeneID; 55876; -.
DR KEGG; hsa:55876; -.
DR MANE-Select; ENST00000418519.6; ENSP00000415049.1; NM_001165958.2; NP_001159430.1.
DR UCSC; uc002htg.3; human. [Q8TAX9-4]
DR CTD; 55876; -.
DR DisGeNET; 55876; -.
DR GeneCards; GSDMB; -.
DR HGNC; HGNC:23690; GSDMB.
DR HPA; ENSG00000073605; Tissue enhanced (intestine, liver, stomach).
DR MIM; 611221; gene.
DR neXtProt; NX_Q8TAX9; -.
DR OpenTargets; ENSG00000073605; -.
DR PharmGKB; PA162390303; -.
DR VEuPathDB; HostDB:ENSG00000073605; -.
DR eggNOG; ENOG502TDKS; Eukaryota.
DR GeneTree; ENSGT00950000183140; -.
DR HOGENOM; CLU_058837_0_0_1; -.
DR InParanoid; Q8TAX9; -.
DR OMA; FPNMERM; -.
DR OrthoDB; 1170047at2759; -.
DR PhylomeDB; Q8TAX9; -.
DR TreeFam; TF331886; -.
DR PathwayCommons; Q8TAX9; -.
DR SignaLink; Q8TAX9; -.
DR BioGRID-ORCS; 55876; 22 hits in 1078 CRISPR screens.
DR ChiTaRS; GSDMB; human.
DR GenomeRNAi; 55876; -.
DR Pharos; Q8TAX9; Tbio.
DR PRO; PR:Q8TAX9; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8TAX9; protein.
DR Bgee; ENSG00000073605; Expressed in rectum and 126 other tissues.
DR ExpressionAtlas; Q8TAX9; baseline and differential.
DR Genevisible; Q8TAX9; HS.
DR GO; GO:0005737; C:cytoplasm; 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:0022829; F:wide pore channel activity; IDA:UniProtKB.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:1902483; P:cytotoxic T cell pyroptotic process; IDA:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central.
DR GO; GO:0140507; P:granzyme-mediated programmed cell death signaling pathway; IDA:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; IDA:UniProtKB.
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 3D-structure; Alternative splicing; Cell membrane; Coiled coil; Cytolysis;
KW Cytoplasm; Direct protein sequencing; Membrane; Necrosis;
KW Reference proteome; Transmembrane; Transmembrane beta strand.
FT CHAIN 1..416
FT /note="Gasdermin-B"
FT /id="PRO_0000329058"
FT CHAIN 1..244
FT /note="Gasdermin-B, N-terminal"
FT /evidence="ECO:0000305|PubMed:32299851"
FT /id="PRO_0000451672"
FT CHAIN 245..416
FT /note="Gasdermin-B, C-terminal"
FT /evidence="ECO:0000305|PubMed:32299851"
FT /id="PRO_0000451673"
FT TRANSMEM 83..100
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
FT TRANSMEM 104..125
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
FT TRANSMEM 168..183
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
FT TRANSMEM 187..199
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
FT REGION 1..280
FT /note="Triggers pyroptosis"
FT /evidence="ECO:0000269|PubMed:27281216"
FT REGION 229..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 248..276
FT /evidence="ECO:0000255"
FT SITE 91..92
FT /note="Cleavage; by CAPS3, CAPS6 and CAPS9"
FT /evidence="ECO:0000305|PubMed:28154144"
FT SITE 229..230
FT /note="Cleavage; by granzyme A"
FT /evidence="ECO:0000269|PubMed:32299851"
FT SITE 244..245
FT /note="Cleavage; by granzyme A"
FT /evidence="ECO:0000269|PubMed:32299851"
FT VAR_SEQ 1..253
FT /note="Missing (in isoform 5)"
FT /id="VSP_061486"
FT VAR_SEQ 221..243
FT /note="NIHFRGKTKSFPEEKDGASSCLG -> R (in isoform 2)"
FT /id="VSP_061487"
FT VAR_SEQ 221..234
FT /note="NIHFRGKTKSFPEE -> K (in isoform 3)"
FT /id="VSP_061488"
FT VAR_SEQ 221
FT /note="N -> SAGLD (in isoform 1)"
FT /id="VSP_061489"
FT VAR_SEQ 234..242
FT /note="Missing (in isoform 6 and isoform 1)"
FT /id="VSP_061490"
FT VARIANT 122
FT /note="E -> G (in dbSNP:rs12450091)"
FT /id="VAR_042632"
FT VARIANT 132
FT /note="T -> A (in dbSNP:rs4619433)"
FT /id="VAR_042633"
FT VARIANT 250
FT /note="D -> G (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_042634"
FT VARIANT 304
FT /note="G -> R (in dbSNP:rs2305479)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_042635"
FT VARIANT 311
FT /note="P -> S (in dbSNP:rs2305480)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_042636"
FT VARIANT 330
FT /note="R -> C (in dbSNP:rs16965388)"
FT /id="VAR_042637"
FT MUTAGEN 229
FT /note="K->A: Does not prevent cleavage by granzyme A
FT (GZMA)."
FT /evidence="ECO:0000269|PubMed:32299851"
FT MUTAGEN 244
FT /note="K->A: Abolished cleavage by granzyme A (GZMA),
FT preventing release of the N-terminal moiety (Gasdermin-B,
FT N-terminal) and ability to induce pyroptosis in target
FT cells of cytotoxic T-cells and natural killer (NK) cells."
FT /evidence="ECO:0000269|PubMed:32299851"
FT CONFLICT 65
FT /note="D -> H (in Ref. 1; AAF69638)"
FT /evidence="ECO:0000305"
FT HELIX 220..224
FT /evidence="ECO:0007829|PDB:5TIB"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:5TIB"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:5TJ4"
FT HELIX 249..261
FT /evidence="ECO:0007829|PDB:5TIB"
FT HELIX 265..276
FT /evidence="ECO:0007829|PDB:5TIB"
FT TURN 277..280
FT /evidence="ECO:0007829|PDB:5TIB"
FT HELIX 282..298
FT /evidence="ECO:0007829|PDB:5TIB"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:5TIB"
FT HELIX 309..313
FT /evidence="ECO:0007829|PDB:5TIB"
FT HELIX 323..337
FT /evidence="ECO:0007829|PDB:5TIB"
FT HELIX 342..352
FT /evidence="ECO:0007829|PDB:5TIB"
FT HELIX 355..365
FT /evidence="ECO:0007829|PDB:5TIB"
FT STRAND 366..368
FT /evidence="ECO:0007829|PDB:5TIB"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:5TJ2"
FT HELIX 384..404
FT /evidence="ECO:0007829|PDB:5TIB"
SQ SEQUENCE 416 AA; 47348 MW; 04DDA43952EF603F CRC64;
MFSVFEEITR IVVKEMDAGG DMIAVRSLVD ADRFRCFHLV GEKRTFFGCR HYTTGLTLMD
ILDTDGDKWL DELDSGLQGQ KAEFQILDNV DSTGELIVRL PKEITISGSF QGFHHQKIKI
SENRISQQYL ATLENRKLKR ELPFSFRSIN TRENLYLVTE TLETVKEETL KSDRQYKFWS
QISQGHLSYK HKGQREVTIP PNRVLSYRVK QLVFPNKETM NIHFRGKTKS FPEEKDGASS
CLGKSLGSED SRNMKEKLED MESVLKDLTE EKRKDVLNSL AKCLGKEDIR QDLEQRVSEV
LISGELHMED PDKPLLSSLF NAAGVLVEAR AKAILDFLDA LLELSEEQQF VAEALEKGTL
PLLKDQVKSV MEQNWDELAS SPPDMDYDPE ARILCALYVV VSILLELAEG PTSVSS
