CASP6 caspase 6, apoptosis-related cysteine peptidase [Homo sapiens] - Gene

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Summary

Official Symbol: CASP6provided by HGNC
Official Full Name: caspase 6, apoptosis-related cysteine peptidaseprovided by HGNC
Primary source: HGNC:1507
See related: Ensembl:ENSG00000138794; HPRD:03321; MIM:601532; Vega:OTTHUMG00000131914
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
Summary: This gene encodes a protein which 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 which undergo proteolytic processing at conserved aspartic 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 two transcript variants that encode different isoforms. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 4q25

Sequence :: Chromosome: 4; NC_000004.11 (110609785..110624629, complement)

See CASP6 in Epigenomics, MapViewer

Chromosome 4 - NC_000004.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Caspase-6 cleaves human TERT at residues E129 and D637 as part of the apoptosis pathway in cultured cells.
Title: The catalytic subunit of human telomerase is a unique caspase-6 and caspase-7 substrate.
Data suggest that Casp4, Casp 6 and TNFSF10 are differentially expressed in potentially fertile and subfertile men and represent useful biomarkers for predicting male fertility in combination with P1 and P2.
Title: Apoptotic gene expression in potentially fertile and subfertile men.
New crystal form of apo-caspase-6 is presented in canonical conformation by identifying the previous apostructure as a hydrogen-ion concentration (pH)-inactivated form of caspase-6.
Title: A new apo-caspase-6 crystal form reveals the active conformation of the apoenzyme.
These data suggest that caspase-6 undergoes a significant conformational change upon substrate binding, adopting a structure that is more like canonical caspases.
Title: Substrate-induced conformational changes occur in all cleaved forms of caspase-6.
CASP6 can be activated and regulated through intramolecular self-cleavage.
Title: Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation.
Intact IRAK-M is strongly expressed in resting alveolar macrophages but is cleaved in patients with pneumonia via neutrophil-mediated induction of CASP-6 activity.
Title: Neutrophils activate alveolar macrophages by producing caspase-6-mediated cleavage of IL-1 receptor-associated kinase-M.
These results imply that pro-Casp6b could negatively regulate pro-Casp6a activation in neurons and prevent Casp6a-mediated axonal degeneration.
Title: Alternatively spliced caspase-6B isoform inhibits the activation of caspase-6A.
The NPM mutant specifically inhibits the activities of the cell-death proteases, caspase-6 and -8, through direct interaction with their cleaved, active forms, but not the immature procaspases.
Title: Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition.
a central and so far underappreciated role of caspase-8 dimerization/dissociation in avoiding unwanted cell death by lethal amplification of caspase responses via the caspase-8, -3, -6 loop.
Title: The caspase-8 dimerization/dissociation balance is a highly potent regulator of caspase-8, -3, -6 signaling.
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
Title: Polymorphisms in the caspase genes and the risk of lung cancer.

Submit: New GeneRIF Correction See all (38)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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HIV-1 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

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_001217.2	NP_002102.2	HTT	BIND	PubMed	Htt interacts with caspase 6.
NP_001217.2	NP_000312.1	RB1	BIND	PubMed	CASP6 (caspase-6) cleaves RB-1 (hRB) at the DSID consensus site to produce the p68 form.
P55212	P05067	APP	HPRD	PubMed
P55212	Q92851	CASP10	HPRD	PubMed
P55212	P42574	CASP3	HPRD	PubMed
P55212	Q14790	CASP8	HPRD	PubMed
P55212	O15519	CFLAR	HPRD	PubMed
P55212	Q12873	CHD3	HPRD	PubMed
P55212	P15924	DSP	HPRD	PubMed
P55212	P05198	EIF2S1	HPRD	PubMed
P55212	P42858	HTT	HPRD	PubMed
P55212	P05783	KRT18	HPRD	PubMed
P55212	P02545	LMNA	HPRD	PubMed
P55212	P20700	LMNB1	HPRD	PubMed
P55212	P10636	MAPT	HPRD	PubMed
P55212	P46934	NEDD4	HPRD	PubMed
P55212	O60285	NUAK1	HPRD	PubMed
P55212	P49585	PCYT1A	HPRD	PubMed
P55212	O60437	PPL	HPRD	PubMed
P55212	Q05513	PRKCZ	HPRD	PubMed
P55212	P49768	PSEN1	HPRD	PubMed
P55212	P49810	PSEN2	HPRD	PubMed
P55212	P61289	PSME3	HPRD	PubMed
P55212	P06400	RB1	HPRD	PubMed
P55212	Q01826	SATB1	HPRD	PubMed
P55212	P11831	SRF	HPRD	PubMed
P55212	O76094	SRP72	HPRD	PubMed
P55212	P05549	TFAP2A	HPRD	PubMed
P55212	P11387	TOP1	HPRD	PubMed
P55212	Q13077	TRAF1	HPRD	PubMed
P55212	O95155	UBE4B	HPRD	PubMed
P55212	P08670	VIM	HPRD	PubMed
	NP_057336.1	BIRC6	BIND	PubMed	BRUCE interacts with Casp-6. This interaction was modeled on a demonstrated interaction between mouse BRUCE and human Casp-6.
BioGRID:107289	BioGRID:107293	CASP10	BioGRID	PubMed	Biochemical Activity
BioGRID:107289	BioGRID:107286	CASP3	BioGRID	PubMed	Biochemical Activity
BioGRID:107289	BioGRID:107289	CASP6	BioGRID	PubMed	Biochemical Activity
BioGRID:107289	BioGRID:107291	CASP8	BioGRID	PubMed	Biochemical Activity
BioGRID:107289	BioGRID:107532	CHD3	BioGRID	PubMed	Two-hybrid
BioGRID:107289	BioGRID:111583	MAPK6	BioGRID	PubMed	Two-hybrid
BioGRID:107289	BioGRID:111317	PIN1	BioGRID	PubMed	Two-hybrid
BioGRID:107289	BioGRID:115717	TAB1	BioGRID	PubMed	Two-hybrid
BioGRID:107289	BioGRID:113037	TRAF1	BioGRID	PubMed	Biochemical Activity
BioGRID:107289	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107289	BioGRID:114757	UBE4A	BioGRID	PubMed	Biochemical Activity
	NP_001158.2	XIAP	BIND	PubMed	XIAP interacts with Casp-6.

Function	Evidence Code	Pubs
cysteine-type endopeptidase activity	TAS Traceable Author Statement more info
cysteine-type peptidase activity	TAS Traceable Author Statement more info	PubMed
peptidase activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acute inflammatory response to non-antigenic stimulus	IEA Inferred from Electronic Annotation more info
apoptotic process	TAS Traceable Author Statement more info
cellular component disassembly involved in apoptosis	TAS Traceable Author Statement more info
induction of apoptosis	TAS Traceable Author Statement more info	PubMed
lens development in camera-type eye	IEA Inferred from Electronic Annotation more info
positive regulation of neuron apoptosis	IEA Inferred from Electronic Annotation more info
positive regulation of retinal cell programmed cell death	IEA Inferred from Electronic Annotation more info
proteolysis	IDA Inferred from Direct Assay more info	PubMed
response to cytokine stimulus	IEA Inferred from Electronic Annotation more info
response to estradiol stimulus	IEA Inferred from Electronic Annotation more info
response to gamma radiation	IEA Inferred from Electronic Annotation more info
response to glucose stimulus	IEA Inferred from Electronic Annotation more info
response to heat	IEA Inferred from Electronic Annotation more info
response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
response to iron ion	IEA Inferred from Electronic Annotation more info
response to organic nitrogen	IEA Inferred from Electronic Annotation more info
response to testosterone stimulus	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: caspase-6

Names: caspase-6; apoptotic protease MCH-2; caspase 6, apoptosis-related cysteine protease

NP_001217.2

EC 3.4.22.59

NP_116787.1

EC 3.4.22.59

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NCBI Reference Sequences (RefSeq)

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_029187.1 RefSeqGene

Range

5001..19845

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001226.3 → NP_001217.2 caspase-6 isoform alpha preproprotein

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

Related

ENSP00000265164, OTTHUMP00000162742, ENST00000265164, OTTHUMT00000254866

Conserved Domains (1) summary

cd00032
Location:37 – 289
Blast Score: 773

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 ...
NM_032992.2 → NP_116787.1 caspase-6 isoform beta

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, OTTHUMP00000162743, ENST00000352981, OTTHUMT00000254867

Conserved Domains (1) summary

cd00032
Location:14 – 200
Blast Score: 576

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 ...

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000004.11 Reference GRCh37.p5 Primary Assembly

Range

110609785..110624629, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000136.1 Alternate HuRef

Range

106342777..106357627, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC004067.1 (116151..130995)	None
genomic	AY254046.1	AAO63494.1
genomic	CH471057.1	EAX06244.1
		EAX06245.1
mRNA	BC000305.2	AAH00305.1
mRNA	BC004460.1	AAH04460.1
mRNA	BM837197.1	None
mRNA	U20536.1	AAC50168.1
mRNA	U20537.1	AAC50169.1
other-genetic	DQ894589.2	ABM85515.1
other-genetic	EU176306.1	ABW03757.1