CASP6 caspase 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CASP6provided by HGNC
Official Full Name: caspase 6provided by HGNC
Primary source: HGNC:HGNC:1507
See related: Ensembl:ENSG00000138794 MIM:601532; AllianceGenome:HGNC:1507
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: MCH2; CSP-6; caspase-6
Summary: This gene encodes a member of the cysteine-aspartic acid protease (caspase) family of enzymes. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic acid residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Alternative splicing of this gene results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Oct 2015]
Expression: Broad expression in duodenum (RPKM 18.7), colon (RPKM 18.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q25

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (109664388..109709767, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (112966324..113010471, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (110609784..110624601, complement)

Chromosome 4 - NC_000004.12 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 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?

NUAK1 promotes metabolic dysfunction-associated steatohepatitis progression by activating Caspase 6-driven pyroptosis and inflammation.
Title: NUAK1 promotes metabolic dysfunction-associated steatohepatitis progression by activating Caspase 6-driven pyroptosis and inflammation.
Caspase 6 promotes innate immune activation by functional crosstalk between RIPK1-IkappaBalpha axis in liver inflammation.
Title: Caspase 6 promotes innate immune activation by functional crosstalk between RIPK1-IκBα axis in liver inflammation.
Caspase-6 is a key regulator of cross-talk signal way in PANoptosis in cancer.
Title: Caspase-6 is a key regulator of cross-talk signal way in PANoptosis in cancer.
Dissection of pyroptosis-related prognostic signature and CASP6-mediated regulation in pancreatic adenocarcinoma: new sights to clinical decision-making.
Title: Dissection of pyroptosis-related prognostic signature and CASP6-mediated regulation in pancreatic adenocarcinoma: new sights to clinical decision-making.
Role of cited-1 and caspase-6 expression in HELLP syndrome.
Title: Role of cited-1 and caspase-6 expression in HELLP syndrome.
Rare CASP6N73T variant associated with hippocampal volume exhibits decreased proteolytic activity, synaptic transmission defect, and neurodegeneration.
Title: Rare CASP6N73T variant associated with hippocampal volume exhibits decreased proteolytic activity, synaptic transmission defect, and neurodegeneration.
Caspase-6-cleaved Tau fails to induce Tau hyperphosphorylation and aggregation, neurodegeneration, glial inflammation, and cognitive deficits.
Title: Caspase-6-cleaved Tau fails to induce Tau hyperphosphorylation and aggregation, neurodegeneration, glial inflammation, and cognitive deficits.
Identification of Allosteric Inhibitors against Active Caspase-6.
Title: Identification of Allosteric Inhibitors against Active Caspase-6.
Results show that two Casp6 variants, Casp6-G66R and Casp6-R65W, have less self-processing and exogenous proteolytic activity than Casp6-WT and reveal a novel regulatory area of Casp6 activity. Furthermore, the existence of these Casp6 variants suggests that full Casp6 activity may be dispensable in humans.
Title: Rare human Caspase-6-R65W and Caspase-6-G66R variants identify a novel regulatory region of Caspase-6 activity.
have identified an exosite on caspase-6 that is critical for protein substrate recognition and turnover and therefore highly relevant for diseases such as cancer in which caspase-6-mediated apoptosis is often disrupted, and in neurodegeneration in which caspase-6 plays a central role.
Title: Tri-arginine exosite patch of caspase-6 recruits substrates for hydrolysis.

Submit: New GeneRIF Correction See all GeneRIFs (68)

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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	The mRNA expression levels for alpha-tubulin, TRADD, IFN-gamma R2, GAS1, MADD, NF-kappaB, I-kappa B, 14-3-3 protein, APaf1, PARP, IGF-1 receptor, RB1, Rb2/p130, ARC, and caspase 6 are upregulated in human neuronal cells after treatment with HIV-1 gp120	PubMed
Vpr	vpr	Exposure of cultured human primary astrocytes to HIV-1 Vpr induces p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury	PubMed
	vpr	Overexpression of caspase-6 is induced by HIV-1 Vpr in the transfected 293T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

csnpcasp6-pcr2-1 (e-PCR)
- UniSTS:257061

csnpcasp6-pcr5-1 (e-PCR)
- UniSTS:257062

csnpcasp6-pcr6-1 (e-PCR)
- UniSTS:257063

D11S2560 (e-PCR)
- UniSTS:37928

CASP6_488 (e-PCR)
- UniSTS:277052

SHGC-51589 (e-PCR)
- UniSTS:60234

D15S1477 (e-PCR)
- UniSTS:474482

SHGC-19815 (e-PCR)
- UniSTS:24695

D4S262 (e-PCR)
- UniSTS:9357

SHGC-19828 (e-PCR)
- UniSTS:1447

RH102859 (e-PCR)
- UniSTS:97193

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
enables cysteine-type endopeptidase activity involved in apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
enables cysteine-type endopeptidase activity involved in execution phase of apoptosis	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type endopeptidase activity involved in execution phase of apoptosis	IMP Inferred from Mutant Phenotype more info	PubMed
enables cysteine-type peptidase activity	TAS Traceable Author Statement more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in activation of innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to staurosporine	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in epithelial cell differentiation	IEP Inferred from Expression Pattern more info	PubMed
involved_in execution phase of apoptosis	IEA Inferred from Electronic Annotation more info
involved_in hepatocyte apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in intrinsic apoptotic signaling pathway by p53 class mediator	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of necroptotic process	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 protein autoprocessing	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in pyroptotic inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of programmed cell death	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: caspase-6

Names: apoptotic protease MCH-2; caspase 6, apoptosis-related cysteine peptidase; caspase 6, apoptosis-related cysteine protease; mammalian Ced-3 homologue 2

NP_001217.2

EC 3.4.22.59

NP_116787.1

EC 3.4.22.59

XP_047272200.1

EC 3.4.22.59

XP_047272201.1

EC 3.4.22.59

XP_054206943.1

EC 3.4.22.59

XP_054206944.1

EC 3.4.22.59

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.

Genomic

NG_029187.2 RefSeqGene

Range

11322..26139

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001226.4 → NP_001217.2 caspase-6 isoform alpha precursor

See identical proteins and their annotated locations for NP_001217.2

Status: REVIEWED

Description

Transcript Variant: This variant (alpha) represents the longer transcript and encodes the longer isoform (alpha).

Source sequence(s)

AC004067, BC000305, U20536

Consensus CDS

CCDS3684.1

UniProtKB/Swiss-Prot

P55212, Q9BQE7

Related

ENSP00000265164.2, ENST00000265164.7

Conserved Domains (1) summary

smart00115
Location:37 → 290

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues
NM_032992.3 → NP_116787.1 caspase-6 isoform beta

See identical proteins and their annotated locations for NP_116787.1

Status: REVIEWED

Description

Transcript Variant: This variant (beta) lacks several exons in the coding region but maintains the reading frame, compared to variant alpha. It encodes isoform beta which is shorter than isoform alpha.

Source sequence(s)

AC004067, BM837197, U20536, U20537

Consensus CDS

CCDS3685.1

UniProtKB/Swiss-Prot

P55212

Related

ENSP00000285333.3, ENST00000352981.7

Conserved Domains (1) summary

cd00032
Location:14 → 200

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...

RNA

NR_133012.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (gamma) lacks an alternate internal exon, compared to variant alpha. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant alpha, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC004067, BX380795, U20536