Casp6
entrez
12368
canonical
uniprot
O08738
canonical
ensembl
ENSMUSG00000027997
resolver
ensp
ENSMUSP00000029626
resolver
enst
ENSMUST00000029626
resolver
genesymbol
Casp6
resolver
genesymbol_syn
Mch2
resolver
uniprot
Q3TPJ9
resolver
uniprot_entry
CASP6_MOUSE
resolver
uniprot_entry
Q3TPJ9_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: During activation, the N-terminal disordered prodomain is removed by cleavage. Concomitantly, double cleavage gives rise to a large 18-kDa and a small 11-kDa subunit. The two large and two small subunits then assemble to form the active CASP6 complex. Can be cleaved and activated by different caspases, depending on the context. Cleaved and activated by caspase-8 (CASP8) and subsequently by caspase-3 (CASP3). Can also undergo autoactivation by mediating autocleavage at Asp-162 and Asp-175, while it is not able to cleave its N-terminal disordered prodomain. Intramolecular cleavage at Asp-175 is a prerequisite for CASP6 self-activation. Cleaved and activated by CASP1 in neurons, possibly in the context of inflammation. Phosphorylation at Ser-239 inhibits autocleavage, preventing caspase activation. {ECO:0000250|UniProtKB:P55212}.
uniprot
proteins
amino_acid_sequence
MTETDGFYKSREVFDPAEQYKMDHKRRGVALIFNHERFFWHLTLPERRGTNADRDNLTRRFSDLGFEVKCFNDLRAEELLLKIHEVSTSSHIDADCFICVFLSHGEGNHVYAYDAKIEIQTLTGLFKGDKCQSLVGKPKIFIIQACRGSQHDVPVVPLDMVDHQTDKLDNVTQVDAASVYTLPAGADFLMCYSVAEGYYSHRETVNGSWYIQDLCEMLARYGSSLEFTELLTLVNRKVSQRRVDFCKDPDAIGKKQVPCFASMLTKKLHFCPKPSK
uniprot
proteins
ec_number
3.4.22.59
uniprot
proteins
function
FUNCTION: Cysteine protease that plays essential roles in programmed cell death, axonal degeneration, development and innate immunity (PubMed:18981099, PubMed:22555455, PubMed:23695670, PubMed:32298652). Acts as a non-canonical executioner caspase during apoptosis: localizes in the nucleus and cleaves the nuclear structural protein NUMA1 and lamin A/LMNA thereby inducing nuclear shrinkage and fragmentation (By similarity). Lamin-A/LMNA cleavage is required for chromatin condensation and nuclear disassembly during apoptotic execution (By similarity). Acts as a regulator of liver damage by promoting hepatocyte apoptosis: in absence of phosphorylation by AMP-activated protein kinase (AMPK), catalyzes cleavage of BID, leading to cytochrome c release, thereby participating in nonalcoholic steatohepatitis (PubMed:32029622). Cleaves PARK7/DJ-1 in cells undergoing apoptosis (PubMed:22555455). Involved in intrinsic apoptosis by mediating cleavage of RIPK1 (By similarity). Furthermore, cleaves many transcription factors such as NF-kappa-B and cAMP response element-binding protein/CREBBP (By similarity). Cleaves phospholipid scramblase proteins XKR4 and XKR9 (PubMed:25231987). In addition to apoptosis, involved in different forms of programmed cell death (PubMed:32298652). Plays an essential role in defense against viruses by acting as a central mediator of the ZBP1-mediated pyroptosis, apoptosis, and necroptosis (PANoptosis), independently of its cysteine protease activity (PubMed:32298652). PANoptosis is a unique inflammatory programmed cell death, which provides a molecular scaffold that allows the interactions and activation of machinery required for inflammasome/pyroptosis, apoptosis and necroptosis (PubMed:32298652). Mechanistically, interacts with RIPK3 and enhances the interaction between RIPK3 and ZBP1, leading to ZBP1-mediated inflammasome activation and cell death (PubMed:32298652). Plays an essential role in axon degeneration during axon pruning which is the remodeling of axons during neurogenesis but not apoptosis (PubMed:23695670). Regulates B-cell programs both during early development and after antigen stimulation (PubMed:18981099, PubMed:29863787). {ECO:0000250|UniProtKB:P55212, ECO:0000269|PubMed:18981099, ECO:0000269|PubMed:22555455, ECO:0000269|PubMed:23695670, ECO:0000269|PubMed:25231987, ECO:0000269|PubMed:29863787, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:32298652}.; FUNCTION: (Microbial infection) Proteolytically cleaves the N protein of coronaviruses. The cleavage leads to two fragments and modulates coronavirus replication by regulating IFN signaling. The two fragments produced by the cleavage interact with IRF3 inhibiting its nuclear translocation after activation and reduce the expression of IFNB and IFN-stimulated genes. {ECO:0000269|PubMed:35922005}.
uniprot
proteins
mass_dalton
31595
uniprot
proteins
mutagenesis
MUTAGEN 146; /note="C->A: Does not affect ability to promote ZBP1-mediated pyroptosis, apoptosis, and necroptosis (PANoptosis)."; /evidence="ECO:0000269|PubMed:32298652
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by NUAK1; phosphorylation inhibits self-activation. Phosphorylation at Ser-239 by AMP-activated protein kinase (PRKAA1 or PRKAA2) inhibits autocleavage, preventing caspase activation, thereby preventing hepatocyte apoptosis. {ECO:0000250|UniProtKB:P55212}.; PTM: Palmitoylation by ZDHHC17 blocks dimerization and subsequent activation, leading to inhibit the cysteine protease activity. {ECO:0000250|UniProtKB:P55212}.; PTM: Can be cleaved and activated by different caspases, depending on the context. Cleaved and activated by caspase-8 (CASP8) and subsequently by caspase-3 (CASP3). Can also undergo autoactivation by mediating autocleavage at Asp-162 and Asp-175, while it is not able to cleave its N-terminal disordered prodomain. Cleaved and activated by CASP1, possibly in the context of inflammation. {ECO:0000250|UniProtKB:P55212}.
uniprot
proteins
protein_family
Peptidase C14A family
uniprot
proteins
pubmed
11062535
uniprot
proteins
pubmed
18981099
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22555455
uniprot
proteins
pubmed
23695670
uniprot
proteins
pubmed
25231987
uniprot
proteins
pubmed
29863787
uniprot
proteins
pubmed
32029622
uniprot
proteins
pubmed
32298652
uniprot
proteins
pubmed
35922005
uniprot
proteins
pubmed
9038361
uniprot
proteins
sequence_length
276
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P55212}. Nucleus {ECO:0000250|UniProtKB:P55212}.
uniprot
proteins