CASP4 caspase 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CASP4provided by HGNC
Official Full Name: caspase 4provided by HGNC
Primary source: HGNC:HGNC:1505
See related: Ensembl:ENSG00000196954 MIM:602664; AllianceGenome:HGNC:1505
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TX; Mih1; ICH-2; Mih1/TX; ICEREL-II; ICE(rel)II
Summary: This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain and a large and small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This caspase is able to cleave and activate its own precursor protein, as well as caspase 1 precursor. When overexpressed, this gene induces cell apoptosis. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in appendix (RPKM 42.7), lymph node (RPKM 37.1) and 24 other tissues See more
Orthologs: all
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Genomic context

Location:: 11q22.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (104942866..104968574, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (104946956..104972673, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (104813593..104839301, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Dectin-1 aggravates neutrophil inflammation through caspase-11/4-mediated macrophage pyroptosis in asthma.
Title: Dectin-1 aggravates neutrophil inflammation through caspase-11/4-mediated macrophage pyroptosis in asthma.
Inflammation in Hypervolemic Hemodialysis Patients: The Roles of RelB and Caspase-4.
Title: Inflammation in Hypervolemic Hemodialysis Patients: The Roles of RelB and Caspase-4.
Structural insights into cytokine cleavage by inflammatory caspase-4.
Title: Structural insights into cytokine cleavage by inflammatory caspase-4.
Intracellular replication of Pseudomonas aeruginosa in epithelial cells requires suppression of the caspase-4 inflammasome.
Title: Intracellular replication of Pseudomonas aeruginosa in epithelial cells requires suppression of the caspase-4 inflammasome.
CASP4/11 Contributes to NLRP3 Activation and COVID-19 Exacerbation.
Title: CASP4/11 Contributes to NLRP3 Activation and COVID-19 Exacerbation.
Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis.
Title: Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis.
CASP4 and CASP8 as newly defined autophagy-pyroptosis-related genes associated with clinical and prognostic features of renal cell carcinoma.
Title: CASP4 and CASP8 as newly defined autophagy-pyroptosis-related genes associated with clinical and prognostic features of renal cell carcinoma.
Caspase-11/4 is involved in bacteria-mediated periodontitis by promoting the release of interleukin-1 beta and tumor necrosis factor-alpha.
Title: Caspase-11/4 is involved in bacteria-mediated periodontitis by promoting the release of interleukin-1 β and tumor necrosis factor-α.
Caspase-4/11 is critical for angiogenesis by repressing Notch1 signalling via inhibiting gamma-secretase activity.
Title: Caspase-4/11 is critical for angiogenesis by repressing Notch1 signalling via inhibiting γ-secretase activity.
Salmonella enterica Serovar Typhimurium Induces NAIP/NLRC4- and NLRP3/ASC-Independent, Caspase-4-Dependent Inflammasome Activation in Human Intestinal Epithelial Cells.
Title: Salmonella enterica Serovar Typhimurium Induces NAIP/NLRC4- and NLRP3/ASC-Independent, Caspase-4-Dependent Inflammasome Activation in Human Intestinal Epithelial Cells.

Submit: New GeneRIF Correction See all GeneRIFs (71)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S1886 (e-PCR), detects polymorphism
- UniSTS:45378

RH16178 (e-PCR)
- UniSTS:79691

D11S3145 (e-PCR)
- UniSTS:152234

D11S4641 (e-PCR)
- UniSTS:42692

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables CARD domain binding	IPI Inferred from Physical Interaction more info	PubMed
NOT enables cysteine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables lipid binding	IDA Inferred from Direct Assay more info	PubMed
enables lipopolysaccharide binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
NOT involved_in apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to amyloid-beta	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to Gram-positive bacterium	IDA Inferred from Direct Assay more info	PubMed
involved_in defense response to bacterium	IDA Inferred from Direct Assay more info	PubMed
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in intrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in non-canonical inflammasome complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-18-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neuron apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of tumor necrosis factor-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autoprocessing	IDA Inferred from Direct Assay more info	PubMed
involved_in protein maturation	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	TAS Traceable Author Statement more info	PubMed
involved_in pyroptotic inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of inflammatory response	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of NLRP1 inflammasome complex	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
part_of non-canonical inflammasome complex	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: caspase-4

Names: CASP-4; ICE and Ced-3 homolog 2; ICE(rel)-II; apoptotic cysteine protease Mih1/TX; caspase 4, apoptosis-related cysteine peptidase; caspase 4, apoptosis-related cysteine protease; protease ICH-2; protease TX

NP_001216.1

EC 3.4.22.57

NP_150649.1

EC 3.4.22.57

XP_011541321.1

EC 3.4.22.57

XP_054226106.1

EC 3.4.22.57

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001225.4 → NP_001216.1 caspase-4 isoform alpha precursor

Status: REVIEWED

Description

Transcript Variant: This variant (alpha) encodes the longest isoform (alpha).

Source sequence(s)

AI128358, AP002004, CN261701, Z48810

Consensus CDS

CCDS8327.1

UniProtKB/Swiss-Prot

A2NHL8, A2NHL9, A2NHM0, B3KPZ9, B4DJH5, B4E2D2, O95601, P49662, Q7KYX7, Q9UG96

Related

ENSP00000388566.2, ENST00000444739.7

Conserved Domains (2) summary

smart00115
Location:126 → 375

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

cd08325
Location:5 → 81

CARD_CASP1-like; Caspase activation and recruitment domain found in Caspase-1 and related proteins
NM_033306.3 → NP_150649.1 caspase-4 isoform gamma precursor

Status: REVIEWED

Description

Transcript Variant: This variant (gamma) includes an alternate exon in the 5' UTR and 5' coding region and uses a downstream in-frame start codon, compared to variant alpha. It encodes isoform gamma, which is shorter than isoform alpha.

Source sequence(s)

AI128358, AP001153, AP002004, U28978

Consensus CDS

CCDS41704.1

UniProtKB/Swiss-Prot

P49662

Related

ENSP00000376857.3, ENST00000393150.7

Conserved Domains (2) summary

smart00115
Location:70 → 319

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

cl14633
Location:1 → 25

DD; Death Domain Superfamily of protein-protein interaction domains

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

104942866..104968574 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011543019.2 → XP_011541321.1 caspase-4 isoform X1

UniProtKB/Swiss-Prot

P49662

Conserved Domains (1) summary

smart00115
Location:35 → 284

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

Reference GRCh38.p14 PATCHES

Genomic

NW_025791791.1 Reference GRCh38.p14 PATCHES

Range

241999..255831 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

104946956..104972673 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054370131.1 → XP_054226106.1 caspase-4 isoform X1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_033307.2: Suppressed sequence

Description

NM_033307.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.