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Gene Section
Short Communication
GSDMB (gasdermin B)
Masaru Tamura, Toshihiko Shiroishi
Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111
Yata, Mishima, Shizuoka, Japan (MT, TS)
Published in Atlas Database: November 2011
Online updated version : http://AtlasGeneticsOncology.org/Genes/GSDMBID43972ch17q12.html
DOI: 10.4267/2042/47298
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
Protein
Other names: GSDML, PRO2521
HGNC (Hugo): GSDMB
Location: 17q12
Local order: ERBB2, GRB7, IKZF3, ZPBP2,
GSDMB, ORMDL3, GSDMA, PSMD3, CSF3.
Description
The full length of GSDMB gene (GSDMB transcript
variant 3) encodes a 416 amino acid protein with
estimated molecular weight of 47345,44 Da. GSDM
family proteins have 9 conserved and unknown
function motifs (motif I to IX). GSDMB lacks motif
VIII where mouse alopecia mutation Rex-denuded
occurs (Runkel et al., 2004; Tamura et al., 2007).
DNA/RNA
Description
Expression
GSDMB belongs to the novel gene family Gasdermin
(GSDM) that consists of four genes in human:
GSDMA, GSDMB, GSDMC and GSDMD (Tamura et
al., 2007). The human GSDMB gene is located on
chromosome 17q21 and consists of 12 exons, spanning
14 kb of genomic DNA.
Expression of GSDMB was observed in esophagus and
gastric epithelium (Saeki et al., 2009). In addition,
GSDMB was frequently expressed in several cancer
tissues and cancer-derived cell lines.
Transcription
Cytoplasm (Carl-McGrath et al., 2008).
GSDMB has at least four alternatively spliced
transcripts variants that range from 1578 to 1646 bp in
length. These splicing variants, which lack exon 6, 7,
and both, are named GSDMB transcript variant 1
(Delta exon 6), GSDMB transcript variant 2 (Delta
exon 6 and exon 7), GSDMB transcript variant 3 (full
length) and GSDMB transcript variant 4 (Delta exon
7). GSDMB has two different promoters, Alu-derived
promoter and long-terminal-repeat (LTR)-derived
promoter (Sin et al., 2006; Huh et al., 2008; Komiyama
et al., 2010). These two promoters drive all GSDMB
transcriptions except for those starting from exon1a and
exon1b.
Function
Pseudogene
Homology
No GSDMB pseudogene has been identified in the
human genome.
GSDMB protein shares homology with other GSDM
family members for N- and C- terminal sequences. Its
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4)
Localisation
The function of GSDMB is largely unknown, because
GSDMB is a novel protein without characteristic
domains related to known function.
Expression level of GSDMB seems to be changed
along progression of several cancers. However, forced
expression of GSDMB could neither promote
malignant transformation of CHO cells nor confer
colony formation ability or carcinogenicity to CHO
cells in nude mice (Sun et al., 2008). Recent large-scale
genome wide association studies (GWAS) revealed that
GSDMB locus is strongly correlated with asthma
(Moffatt et al., 2010).
271
GSDMB (gasdermin B)
Tamura M, Shiroishi T
Runkel F, Marquardt A, Stoeger C, Kochmann E, Simon D,
Kohnke B, Korthaus D, Wattler F, Fuchs H, Hrabé de Angelis
M, Stumm G, Nehls M, Wattler S, Franz T, Augustin M. The
dominant alopecia phenotypes Bareskin, Rex-denuded, and
Reduced Coat 2 are caused by mutations in gasdermin 3.
Genomics. 2004 Nov;84(5):824-35
N-terminal sequence is also shared by DFNA5
(deafness, autosomal dominant 5) and DFNB59
(deafness, autosomal recessive 59, also known as
pejvakin), although the extent of similarity to these
proteins is lower than to the other GSDM family
members.
GSDMB ortholog is identified in the chimpanzee, dog
and cow, but not in the rat and mouse (Katoh and
Katoh, 2004; Tamura et al., 2007).
Sin HS, Huh JW, Kim DS, Kang DW, Min DS, Kim TH, Ha HS,
Kim HH, Lee SY, Kim HS. Transcriptional control of the HERVH LTR element of the GSDML gene in human tissues and
cancer cells. Arch Virol. 2006 Oct;151(10):1985-94
Tamura M, Tanaka S, Fujii T, Aoki A, Komiyama H, Ezawa K,
Sumiyama K, Sagai T, Shiroishi T. Members of a novel gene
family, Gsdm, are expressed exclusively in the epithelium of
the skin and gastrointestinal tract in a highly tissue-specific
manner. Genomics. 2007 May;89(5):618-29
Mutations
Note
No human GSDMB mutations have been reported to
date.
Huh JW, Kim DS, Kang DW, Ha HS, Ahn K, Noh YN, Min DS,
Chang KT, Kim HS. Transcriptional regulation of GSDML gene
by antisense-oriented HERV-H LTR element. Arch Virol.
2008;153(6):1201-5
Germinal
Not known.
Carl-McGrath S, Schneider-Stock R, Ebert M, Röcken C.
Differential expression and localisation of gasdermin-like
(GSDML), a novel member of the cancer-associated GSDMDC
protein family, in neoplastic and non-neoplastic gastric,
hepatic, and colon tissues. Pathology. 2008 Jan;40(1):13-24
Somatic
Not known.
Implicated in
Various cancers
Sun Q, Yang J, Xing G, Sun Q, Zhang L, He F. Expression of
GSDML Associates with Tumor Progression in Uterine Cervix
Cancer. Transl Oncol. 2008 Jul;1(2):73-83
Note
GSDMB is up-regulated in several cancers, such as
gastric, colorectal, hepatic, cervical carcinomas,
suggesting the possibility that it is used as a marker for
cancer development and progression.
Saeki N, Usui T, Aoyagi K, Kim DH, Sato M, Mabuchi T,
Yanagihara K, Ogawa K, Sakamoto H, Yoshida T, Sasaki H.
Distinctive expression and function of four GSDM family genes
(GSDMA-D) in normal and malignant upper gastrointestinal
epithelium.
Genes
Chromosomes
Cancer.
2009
Mar;48(3):261-71
Asthma
Komiyama H, Aoki A, Tanaka S, Maekawa H, Kato Y, Wada R,
Maekawa T, Tamura M, Shiroishi T. Alu-derived cis-element
regulates tumorigenesis-dependent gastric expression of
GASDERMIN B (GSDMB). Genes Genet Syst. 2010
Feb;85(1):75-83
Note
The genome wide association study (GWAS)
demonstrated that GSDMB locus is strongly associated
with asthma (Moffatt et al., 2010).
Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E,
Heath S, von Mutius E, Farrall M, Lathrop M, Cookson WO. A
large-scale, consortium-based genomewide association study
of asthma. N Engl J Med. 2010 Sep 23;363(13):1211-21
References
Katoh M, Katoh M. Evolutionary recombination hotspot around
GSDML-GSDM locus is closely linked to the oncogenomic
recombination hotspot around the PPP1R1B-ERBB2-GRB7
amplicon. Int J Oncol. 2004 Apr;24(4):757-63
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4)
This article should be referenced as such:
Tamura M, Shiroishi T. GSDMB (gasdermin B). Atlas Genet
Cytogenet Oncol Haematol. 2012; 16(4):271-272.
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