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Protein

Gasdermin-D

Gene

GSDMD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of inflammasomes responsible for the execution of pyroptosis and the release of mature IL1B. In response to canonical, as well as non-canonical(such as cytosolic LPS) inflammasome activators, undergoes cleavage by inflammatory caspases CASP1 and CASP4, respectively. The released N-terminal moiety promotes pyroptosis and release of mature IL1B.By similarity2 Publications

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity, Necrosis

Names & Taxonomyi

Protein namesi
Recommended name:
Gasdermin-D
Alternative name(s):
Gasdermin domain-containing protein 1
Gene namesi
Name:GSDMD
Synonyms:DFNA5L, GSDMDC1
ORF Names:FKSG10
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:25697. GSDMD.

Subcellular locationi

  • Inflammasome By similarity

  • Note: In response to a canonical inflammasome stimulus, such as nigericin, recruited to NLRP3 inflammasone with similar kinetics to that of proCASP1.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Inflammasome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi275 – 2751D → A: Loss of cleavage by CASP1 and CASP4 and LPS-induced pyroptosis. 1 Publication

Organism-specific databases

PharmGKBiPA162390357.

Polymorphism and mutation databases

BioMutaiGSDMD.
DMDMi13124058.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 484484Gasdermin-DPRO_0000148175Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei37 – 371PhosphotyrosineCombined sources
Modified residuei158 – 1581PhosphotyrosineCombined sources
Modified residuei185 – 1851PhosphoserineCombined sources

Post-translational modificationi

Cleavage at Asp-275 by CASP1 (mature and uncleaved precursor forms) or CASP4 relieves autoinhibition and is sufficient to initiate pyroptosis.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei275 – 2762Cleavage (by inflammatory caspases CASP1 and CASP4)1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP57764.
MaxQBiP57764.
PaxDbiA8K702.
P57764.
PRIDEiP57764.

PTM databases

iPTMnetiP57764.
PhosphoSiteiP57764.

Expressioni

Tissue specificityi

Expressed in the suprabasal cells of esophagus, as well as in the isthmus/neck, pit, and gland of the stomach, suggesting preferential expression in differentiating cells.1 Publication

Gene expression databases

BgeeiP57764.
CleanExiHS_GSDMD.
ExpressionAtlasiP57764. baseline and differential.
GenevisibleiP57764. HS.

Organism-specific databases

HPAiCAB004656.
HPA044487.

Interactioni

Subunit structurei

In response to a canonical inflammasome stimulus, such as nigericin, recruited to NLRP3 inflammasone with similar kinetics to that of proCASP1. Although this recruitment is also observed in the absence of PYCARD, it is more efficient in its presence of PYCARD.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
KCTD6Q8NC693EBI-2798865,EBI-2511344

Protein-protein interaction databases

BioGridi122891. 1 interaction.
DIPiDIP-61775N.
IntActiP57764. 4 interactions.
STRINGi9606.ENSP00000262580.

Structurei

3D structure databases

ProteinModelPortaliP57764.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 243243Triggers pyroptosis1 PublicationAdd
BLAST

Domaini

Intramolecular interactions between N- and C-terminal domains may be important for autoinhibition in the absence of cleavage by inflammatory caspases CASP1 or CASP4. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain that is released upon cleavage by inflammatory caspases.1 Publication

Sequence similaritiesi

Belongs to the gasdermin family.Curated

Phylogenomic databases

eggNOGiENOG410IKA4. Eukaryota.
ENOG4111D9N. LUCA.
GeneTreeiENSGT00530000063218.
HOGENOMiHOG000082450.
HOVERGENiHBG099862.
InParanoidiP57764.
OrthoDBiEOG71K636.
PhylomeDBiP57764.
TreeFamiTF331886.

Family and domain databases

InterProiIPR007677. Gasdermin.
[Graphical view]
PANTHERiPTHR16399. PTHR16399. 1 hit.
PfamiPF04598. Gasdermin. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P57764-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSAFERVVR RVVQELDHGG EFIPVTSLQS STGFQPYCLV VRKPSSSWFW
60 70 80 90 100
KPRYKCVNLS IKDILEPDAA EPDVQRGRSF HFYDAMDGQI QGSVELAAPG
110 120 130 140 150
QAKIAGGAAV SDSSSTSMNV YSLSVDPNTW QTLLHERHLR QPEHKVLQQL
160 170 180 190 200
RSRGDNVYVV TEVLQTQKEV EVTRTHKREG SGRFSLPGAT CLQGEGQGHL
210 220 230 240 250
SQKKTVTIPS GSTLAFRVAQ LVIDSDLDVL LFPDKKQRTF QPPATGHKRS
260 270 280 290 300
TSEGAWPQLP SGLSMMRCLH NFLTDGVPAE GAFTEDFQGL RAEVETISKE
310 320 330 340 350
LELLDRELCQ LLLEGLEGVL RDQLALRALE EALEQGQSLG PVEPLDGPAG
360 370 380 390 400
AVLECLVLSS GMLVPELAIP VVYLLGALTM LSETQHKLLA EALESQTLLG
410 420 430 440 450
PLELVGSLLE QSAPWQERST MSLPPGLLGN SWGEGAPAWV LLDECGLELG
460 470 480
EDTPHVCWEP QAQGRMCALY ASLALLSGLS QEPH
Length:484
Mass (Da):52,801
Last modified:February 21, 2001 - v1
Checksum:iF7CE8073E0C0194D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti360 – 483124SGMLV…LSQEP → PECWCRNSLSLLSTCWG in AAG22861 (Ref. 1) CuratedAdd
BLAST
Sequence conflicti386 – 3861H → R in BAF84506 (PubMed:14702039).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY008304 mRNA. Translation: AAG22861.1.
AK022212 mRNA. Translation: BAB13986.1.
AK291817 mRNA. Translation: BAF84506.1.
AC067930 Genomic DNA. No translation available.
CH471162 Genomic DNA. Translation: EAW82243.1.
CH471162 Genomic DNA. Translation: EAW82245.1.
BC008904 mRNA. Translation: AAH08904.1.
BC069000 mRNA. Translation: AAH69000.1.
CCDSiCCDS34956.1.
RefSeqiNP_001159709.1. NM_001166237.1.
NP_079012.3. NM_024736.6.
UniGeneiHs.118983.

Genome annotation databases

EnsembliENST00000262580; ENSP00000262580; ENSG00000104518.
ENST00000526406; ENSP00000433209; ENSG00000104518.
ENST00000615119; ENSP00000482096; ENSG00000278718.
ENST00000631751; ENSP00000488012; ENSG00000278718.
GeneIDi79792.
KEGGihsa:79792.
UCSCiuc003yyg.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY008304 mRNA. Translation: AAG22861.1.
AK022212 mRNA. Translation: BAB13986.1.
AK291817 mRNA. Translation: BAF84506.1.
AC067930 Genomic DNA. No translation available.
CH471162 Genomic DNA. Translation: EAW82243.1.
CH471162 Genomic DNA. Translation: EAW82245.1.
BC008904 mRNA. Translation: AAH08904.1.
BC069000 mRNA. Translation: AAH69000.1.
CCDSiCCDS34956.1.
RefSeqiNP_001159709.1. NM_001166237.1.
NP_079012.3. NM_024736.6.
UniGeneiHs.118983.

3D structure databases

ProteinModelPortaliP57764.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122891. 1 interaction.
DIPiDIP-61775N.
IntActiP57764. 4 interactions.
STRINGi9606.ENSP00000262580.

PTM databases

iPTMnetiP57764.
PhosphoSiteiP57764.

Polymorphism and mutation databases

BioMutaiGSDMD.
DMDMi13124058.

Proteomic databases

EPDiP57764.
MaxQBiP57764.
PaxDbiA8K702.
P57764.
PRIDEiP57764.

Protocols and materials databases

DNASUi79792.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262580; ENSP00000262580; ENSG00000104518.
ENST00000526406; ENSP00000433209; ENSG00000104518.
ENST00000615119; ENSP00000482096; ENSG00000278718.
ENST00000631751; ENSP00000488012; ENSG00000278718.
GeneIDi79792.
KEGGihsa:79792.
UCSCiuc003yyg.4. human.

Organism-specific databases

CTDi79792.
GeneCardsiGSDMD.
HGNCiHGNC:25697. GSDMD.
HPAiCAB004656.
HPA044487.
neXtProtiNX_P57764.
PharmGKBiPA162390357.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKA4. Eukaryota.
ENOG4111D9N. LUCA.
GeneTreeiENSGT00530000063218.
HOGENOMiHOG000082450.
HOVERGENiHBG099862.
InParanoidiP57764.
OrthoDBiEOG71K636.
PhylomeDBiP57764.
TreeFamiTF331886.

Miscellaneous databases

ChiTaRSiGSDMD. human.
GenomeRNAii79792.
NextBioi69324.
PROiP57764.

Gene expression databases

BgeeiP57764.
CleanExiHS_GSDMD.
ExpressionAtlasiP57764. baseline and differential.
GenevisibleiP57764. HS.

Family and domain databases

InterProiIPR007677. Gasdermin.
[Graphical view]
PANTHERiPTHR16399. PTHR16399. 1 hit.
PfamiPF04598. Gasdermin. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of FKSG10, a novel gene related to breast cancer."
    Wang Y.-G.
    Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Mammary gland.
  3. "DNA sequence and analysis of human chromosome 8."
    Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T.
    , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
    Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Lymph and Salivary gland.
  6. "Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death."
    Shi J., Zhao Y., Wang K., Shi X., Wang Y., Huang H., Zhuang Y., Cai T., Wang F., Shao F.
    Nature 526:660-665(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 276-281, FUNCTION, CLEAVAGE BY CASP1 AND CASP4, MUTAGENESIS OF ASP-275, AUTOINHIBITION.
  7. "Identification and characterization of human DFNA5L, mouse Dfna5l, and rat Dfna5l genes in silico."
    Katoh M., Katoh M.
    Int. J. Oncol. 25:765-770(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: GENE STRUCTURE.
  8. "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
    Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
    Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-37 AND TYR-158, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  10. "Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium."
    Saeki N., Usui T., Aoyagi K., Kim D.H., Sato M., Mabuchi T., Yanagihara K., Ogawa K., Sakamoto H., Yoshida T., Sasaki H.
    Genes Chromosomes Cancer 48:261-271(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  11. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  13. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  14. Cited for: FUNCTION, CLEAVAGE BY CASP4.
  15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiGSDMD_HUMAN
AccessioniPrimary (citable) accession number: P57764
Secondary accession number(s): A8K702, D3DWJ9, Q96Q98
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: May 11, 2016
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.