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CASP4 caspase 4 [ Homo sapiens (human) ]

Gene ID: 837, updated on 13-Apr-2024

Summary

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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

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See CASP4 in Genome Data Viewer
Location:
11q22.3
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (104942866..104968574, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (104946956..104972673, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (104813593..104839301, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene NANOG hESC enhancer GRCh37_chr11:104765419-104765947 Neighboring gene caspase 12 (gene/pseudogene) Neighboring gene caspase 4 like, pseudogene Neighboring gene uncharacterized LOC124902813 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr11:104839101-104840300 Neighboring gene Sharpr-MPRA regulatory region 11455 Neighboring gene caspase 5 Neighboring gene uncharacterized LOC124902742 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5460 Neighboring gene caspase 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Caspase-4/11 is critical for angiogenesis by repressing Notch1 signalling via inhibiting γ-secretase activity. Fan L, et al. Br J Pharmacol, 2022 Oct. PMID 35737588
  2. Expression of human caspase-4 in the gingival epithelium affected with periodontitis: Its involvement in Porphyromonas gingivalis-challenged gingival epithelial cells. Kantrong N, et al. Arch Oral Biol, 2022 Aug. PMID 35640321
  3. CASP4 gene silencing in epithelial cancer cells leads to impairment of cell migration, cell-matrix adhesion and tissue invasion. Papoff G, et al. Sci Rep, 2018 Dec 7. PMID 30531914, Free PMC Article
  4. Entamoeba histolytica-induced IL-1β secretion is dependent on caspase-4 and gasdermin D. Quach J, et al. Mucosal Immunol, 2019 Mar. PMID 30361535
  5. A Type III Effector NleF from EHEC Inhibits Epithelial Inflammatory Cell Death by Targeting Caspase-4. Song T, et al. Biomed Res Int, 2017. PMID 28593173, Free PMC Article

See all (110) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. Structural insights into cytokine cleavage by inflammatory caspase-4.
    Title: Structural insights into cytokine cleavage by inflammatory caspase-4.
  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.
  5. CASP4/11 Contributes to NLRP3 Activation and COVID-19 Exacerbation.
    Title: CASP4/11 Contributes to NLRP3 Activation and COVID-19 Exacerbation.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables CARD domain binding IPI
Inferred from Physical Interaction
more info
 PubMed 
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 
NOT enables cysteine-type endopeptidase activity involved in apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
  
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 inflammatory response IEA
Inferred from Electronic Annotation
more info
  
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 pyroptosis 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 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
NP_150649.1
XP_011541321.1
XP_054226106.1

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)

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

    See identical proteins and their annotated locations for NP_001216.1

    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

  2. NM_033306.3 → NP_150649.1  caspase-4 isoform gamma precursor

    See identical proteins and their annotated locations for NP_150649.1

    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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    104942866..104968574 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    See identical proteins and their annotated locations for XP_011541321.1

    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

  1. NW_025791791.1 Reference GRCh38.p14 PATCHES

    Range
    241999..255831 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    104946956..104972673 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_033307.2: Suppressed sequence

    Description
    NM_033307.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P49662.1 GenPept UniProtKB/Swiss-Prot:P49662

Gene LinkOut

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