UniProt functional annotation for Q8TAX9



	UniProt functional annotation for Q8TAX9

UniProt code: Q8TAX9.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: [Gasdermin-B]: Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death (PubMed:32299851). This form constitutes the precursor of the pore- forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-B, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:32299851). {ECO:0000269|PubMed:32299851}.

Function: [Gasdermin-B, N-terminal]: Pore-forming protein produced by cleavage by granzyme A (GZMA), which causes membrane permeabilization and pyroptosis in target cells of cytotoxic T and natural killer (NK) cells (PubMed:27281216, PubMed:32299851). Key downstream mediator of granzyme-mediated cell death: (1) granzyme A (GZMA), delivered to target cells from cytotoxic T- and NK-cells, (2) specifically cleaves Gasdermin-B to generate this form (PubMed:32299851). After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:32299851). Binds to membrane inner leaflet lipids, such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5- phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, and more weakly to phosphatidic acid (PubMed:28154144). Also binds sufatide, a component of the apical membrane of epithelial cells (PubMed:28154144). {ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:28154144, ECO:0000269|PubMed:32299851}.

Activity regulation: [Gasdermin-B]: The full-length protein before cleavage is inactive: intramolecular interactions between N- and C- terminal domains mediate autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-B, N-terminal) following cleavage by granzyme A (GZMA) (PubMed:32299851). {ECO:0000250|UniProtKB:Q5Y4Y6, ECO:0000269|PubMed:32299851}.

Subunit: [Gasdermin-B, N-terminal]: Homooligomer; homooligomeric ring- shaped pore complex containing 27-28 subunits when inserted in the membrane. {ECO:0000250|UniProtKB:Q5Y4Y6}.

Subcellular location: [Gasdermin-B]: Cytoplasm {ECO:0000269|PubMed:18038310}. Note=Vesicular localization in the apical region of gastric chief cells and colonic surface mucous cells, and the basal region of neuroendocrine cells. {ECO:0000269|PubMed:18038310}.

Subcellular location: [Gasdermin-B, N-terminal]: Cell membrane {ECO:0000250|UniProtKB:Q5Y4Y6}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q5Y4Y6}.

Tissue specificity: In the gastrointestinal tract, expressed in proliferating cells, including in the basal cell layer of esophagus and in isthmus/neck of stomach. {ECO:0000269|PubMed:19051310}.

Induction: Expression is induced by interferon-gamma (IFNG). {ECO:0000269|PubMed:32299851}.

Domain: Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain. {ECO:0000250|UniProtKB:Q5Y4Y6}.

Ptm: Cleavage by granzyme A (GZMA) relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-B, N-terminal) that initiates pyroptosis (PubMed:32299851). Not cleaved by other granzymes (PubMed:32299851). Major cleavage site takes places after Lys-239; a minor cleavage site takes place after Lys-233 (PubMed:32299851). {ECO:0000269|PubMed:32299851}.

Miscellaneous: Long terminal repeat (LTR) of endogenous retrovirus HERV-H with reverse orientation may serve as alternative promoters of GSDML gene. {ECO:0000269|PubMed:16625320}.

Miscellaneous: GSDML may be used as predictive markers of cervical lymph node metastasis and may help, with a panel of other genes, to discriminate between primary tumors of oral squamous cell carcinoma that metastasize to cervical lymph node and those that do not metastasize. {ECO:0000269|PubMed:17391312}.

Similarity: Belongs to the gasdermin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		[Gasdermin-B]: Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death (PubMed:32299851). This form constitutes the precursor of the pore- forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-B, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:32299851). {ECO:0000269\|PubMed:32299851}.



Function:		[Gasdermin-B, N-terminal]: Pore-forming protein produced by cleavage by granzyme A (GZMA), which causes membrane permeabilization and pyroptosis in target cells of cytotoxic T and natural killer (NK) cells (PubMed:27281216, PubMed:32299851). Key downstream mediator of granzyme-mediated cell death: (1) granzyme A (GZMA), delivered to target cells from cytotoxic T- and NK-cells, (2) specifically cleaves Gasdermin-B to generate this form (PubMed:32299851). After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:32299851). Binds to membrane inner leaflet lipids, such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5- phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, and more weakly to phosphatidic acid (PubMed:28154144). Also binds sufatide, a component of the apical membrane of epithelial cells (PubMed:28154144). {ECO:0000269\|PubMed:27281216, ECO:0000269\|PubMed:28154144, ECO:0000269\|PubMed:32299851}.


Activity regulation:		[Gasdermin-B]: The full-length protein before cleavage is inactive: intramolecular interactions between N- and C- terminal domains mediate autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-B, N-terminal) following cleavage by granzyme A (GZMA) (PubMed:32299851). {ECO:0000250\|UniProtKB:Q5Y4Y6, ECO:0000269\|PubMed:32299851}.
Subunit:		[Gasdermin-B, N-terminal]: Homooligomer; homooligomeric ring- shaped pore complex containing 27-28 subunits when inserted in the membrane. {ECO:0000250\|UniProtKB:Q5Y4Y6}.
Subcellular location:		[Gasdermin-B]: Cytoplasm {ECO:0000269\|PubMed:18038310}. Note=Vesicular localization in the apical region of gastric chief cells and colonic surface mucous cells, and the basal region of neuroendocrine cells. {ECO:0000269\|PubMed:18038310}.
Subcellular location:		[Gasdermin-B, N-terminal]: Cell membrane {ECO:0000250\|UniProtKB:Q5Y4Y6}; Multi-pass membrane protein {ECO:0000250\|UniProtKB:Q5Y4Y6}.
Tissue specificity:		In the gastrointestinal tract, expressed in proliferating cells, including in the basal cell layer of esophagus and in isthmus/neck of stomach. {ECO:0000269\|PubMed:19051310}.
Induction:		Expression is induced by interferon-gamma (IFNG). {ECO:0000269\|PubMed:32299851}.
Domain:		Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain. {ECO:0000250\|UniProtKB:Q5Y4Y6}.
Ptm:		Cleavage by granzyme A (GZMA) relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-B, N-terminal) that initiates pyroptosis (PubMed:32299851). Not cleaved by other granzymes (PubMed:32299851). Major cleavage site takes places after Lys-239; a minor cleavage site takes place after Lys-233 (PubMed:32299851). {ECO:0000269\|PubMed:32299851}.
Miscellaneous:		Long terminal repeat (LTR) of endogenous retrovirus HERV-H with reverse orientation may serve as alternative promoters of GSDML gene. {ECO:0000269\|PubMed:16625320}.
Miscellaneous:		GSDML may be used as predictive markers of cervical lymph node metastasis and may help, with a panel of other genes, to discriminate between primary tumors of oral squamous cell carcinoma that metastasize to cervical lymph node and those that do not metastasize. {ECO:0000269\|PubMed:17391312}.
Similarity:		Belongs to the gasdermin family. {ECO:0000305}.