UniProtKB - O08738 (CASP6_MOUSE)
Caspase-6
Casp6
Functioni
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).
By similarity7 PublicationsCatalytic activityi
- Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp-|-.2 Publications EC:3.4.22.59
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 104 | By similarity | 1 | |
Active sitei | 146 | 1 Publication | 1 |
GO - Molecular functioni
- cysteine-type endopeptidase activity Source: UniProtKB
- cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
- cysteine-type endopeptidase activity involved in execution phase of apoptosis Source: MGI
- endopeptidase activity Source: MGI
- identical protein binding Source: MGI
GO - Biological processi
- activation of innate immune response Source: UniProtKB
- acute inflammatory response to non-antigenic stimulus Source: MGI
- apoptotic process Source: GO_Central
- axonal fasciculation Source: MGI
- cellular response to staurosporine Source: MGI
- epithelial cell differentiation Source: Ensembl
- hepatocyte apoptotic process Source: UniProtKB
- intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of necroptotic process Source: UniProtKB
- positive regulation of neuron apoptotic process Source: MGI
- positive regulation of retinal cell programmed cell death Source: MGI
- protein autoprocessing Source: UniProtKB
- proteolysis Source: MGI
- pyroptosis Source: UniProtKB
- response to cytokine Source: MGI
- response to glucose Source: MGI
- response to hydrogen peroxide Source: MGI
- response to iron ion Source: MGI
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Apoptosis |
Enzyme and pathway databases
BRENDAi | 3.4.22.59, 3474 |
Reactomei | R-MMU-111465, Apoptotic cleavage of cellular proteins R-MMU-264870, Caspase-mediated cleavage of cytoskeletal proteins R-MMU-352238, Breakdown of the nuclear lamina |
Protein family/group databases
MEROPSi | C14.005 |
Names & Taxonomyi
Protein namesi | Recommended name: Caspase-61 Publication (EC:3.4.22.592 Publications)Short name: CASP-61 Publication Alternative name(s): Apoptotic protease Mch-21 Publication Cleaved into the following 2 chains: Caspase-6 subunit p18By similarity Caspase-6 subunit p11By similarity |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1312921, Casp6 |
VEuPathDBi | HostDB:ENSMUSG00000027997 |
Subcellular locationi
Cytosol
- cytosol Source: MGI
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: UniProtKB
Other locations
- axon Source: MGI
- cytoplasm Source: UniProtKB
- neuronal cell body Source: MGI
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 146 | C → A: Does not affect ability to promote ZBP1-mediated pyroptosis, apoptosis, and necroptosis (PANoptosis). 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
PropeptideiPRO_0000004612 | 1 – 5 | By similarity | 5 | |
ChainiPRO_0000004613 | 6 – 162 | Caspase-6 subunit p18By similarityAdd BLAST | 157 | |
PropeptideiPRO_0000004614 | 163 – 175 | By similarityAdd BLAST | 13 | |
ChainiPRO_0000004615 | 176 – 276 | Caspase-6 subunit p11By similarityAdd BLAST | 101 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 62 | PhosphoserineCombined sources | 1 | |
Modified residuei | 239 | PhosphoserineBy similarity | 1 | |
Lipidationi | 246 | S-palmitoyl cysteineBy similarity | 1 | |
Lipidationi | 259 | S-palmitoyl cysteineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Autocatalytic cleavage, Lipoprotein, Palmitate, Phosphoprotein, ZymogenProteomic databases
EPDi | O08738 |
jPOSTi | O08738 |
PaxDbi | O08738 |
PeptideAtlasi | O08738 |
PRIDEi | O08738 |
ProteomicsDBi | 265440 |
PTM databases
iPTMneti | O08738 |
PhosphoSitePlusi | O08738 |
SwissPalmi | O08738 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000027997, Expressed in stomach and 277 other tissues |
Genevisiblei | O08738, MM |
Interactioni
Subunit structurei
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 11 kDa (p11) subunit.
Interacts with BIRC6/bruce.
Interacts with RIPK3.
By similarityHeterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (Caspase-6 subunit p18) and a 11 kDa (Caspase-6 subunit p11) subunit.
By similarityHeterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (Caspase-6 subunit p18) and a 11 kDa (Caspase-6 subunit p11) subunit.
By similarityGO - Molecular functioni
- identical protein binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 198498, 13 interactors |
ComplexPortali | CPX-3944, Caspase-6 complex |
STRINGi | 10090.ENSMUSP00000029626 |
Miscellaneous databases
RNActi | O08738, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 25 – 27 | Tri-arginine exositeBy similarity | 3 | |
Regioni | 108 – 125 | 130's regionBy similarityAdd BLAST | 18 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3573, Eukaryota |
GeneTreei | ENSGT00940000155140 |
HOGENOMi | CLU_036904_2_0_1 |
InParanoidi | O08738 |
OMAi | ACRGSQH |
OrthoDBi | 984395at2759 |
PhylomeDBi | O08738 |
TreeFami | TF102023 |
Family and domain databases
CDDi | cd00032, CASc, 1 hit |
InterProi | View protein in InterPro IPR029030, Caspase-like_dom_sf IPR037554, Caspase_6 IPR033139, Caspase_cys_AS IPR016129, Caspase_his_AS IPR002398, Pept_C14 IPR002138, Pept_C14_p10 IPR001309, Pept_C14_p20 IPR015917, Pept_C14A |
PANTHERi | PTHR10454, PTHR10454, 1 hit PTHR10454:SF206, PTHR10454:SF206, 1 hit |
PRINTSi | PR00376, IL1BCENZYME |
SMARTi | View protein in SMART SM00115, CASc, 1 hit |
SUPFAMi | SSF52129, SSF52129, 1 hit |
PROSITEi | View protein in PROSITE PS01122, CASPASE_CYS, 1 hit PS01121, CASPASE_HIS, 1 hit PS50207, CASPASE_P10, 1 hit PS50208, CASPASE_P20, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MTETDGFYKS REVFDPAEQY KMDHKRRGVA LIFNHERFFW HLTLPERRGT
60 70 80 90 100
NADRDNLTRR FSDLGFEVKC FNDLRAEELL LKIHEVSTSS HIDADCFICV
110 120 130 140 150
FLSHGEGNHV YAYDAKIEIQ TLTGLFKGDK CQSLVGKPKI FIIQACRGSQ
160 170 180 190 200
HDVPVVPLDM VDHQTDKLDN VTQVDAASVY TLPAGADFLM CYSVAEGYYS
210 220 230 240 250
HRETVNGSWY IQDLCEMLAR YGSSLEFTEL LTLVNRKVSQ RRVDFCKDPD
260 270
AIGKKQVPCF ASMLTKKLHF CPKPSK
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y13087 mRNA Translation: CAA73529.1 |
CCDSi | CCDS17838.1 |
RefSeqi | NP_033941.3, NM_009811.4 |
Genome annotation databases
Ensembli | ENSMUST00000029626; ENSMUSP00000029626; ENSMUSG00000027997 |
GeneIDi | 12368 |
KEGGi | mmu:12368 |
UCSCi | uc008riq.3, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y13087 mRNA Translation: CAA73529.1 |
CCDSi | CCDS17838.1 |
RefSeqi | NP_033941.3, NM_009811.4 |
3D structure databases
SMRi | O08738 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 198498, 13 interactors |
ComplexPortali | CPX-3944, Caspase-6 complex |
STRINGi | 10090.ENSMUSP00000029626 |
Protein family/group databases
MEROPSi | C14.005 |
PTM databases
iPTMneti | O08738 |
PhosphoSitePlusi | O08738 |
SwissPalmi | O08738 |
Proteomic databases
EPDi | O08738 |
jPOSTi | O08738 |
PaxDbi | O08738 |
PeptideAtlasi | O08738 |
PRIDEi | O08738 |
ProteomicsDBi | 265440 |
Protocols and materials databases
Antibodypediai | 1733, 1146 antibodies from 43 providers |
DNASUi | 12368 |
Genome annotation databases
Ensembli | ENSMUST00000029626; ENSMUSP00000029626; ENSMUSG00000027997 |
GeneIDi | 12368 |
KEGGi | mmu:12368 |
UCSCi | uc008riq.3, mouse |
Organism-specific databases
CTDi | 839 |
MGIi | MGI:1312921, Casp6 |
VEuPathDBi | HostDB:ENSMUSG00000027997 |
Phylogenomic databases
eggNOGi | KOG3573, Eukaryota |
GeneTreei | ENSGT00940000155140 |
HOGENOMi | CLU_036904_2_0_1 |
InParanoidi | O08738 |
OMAi | ACRGSQH |
OrthoDBi | 984395at2759 |
PhylomeDBi | O08738 |
TreeFami | TF102023 |
Enzyme and pathway databases
BRENDAi | 3.4.22.59, 3474 |
Reactomei | R-MMU-111465, Apoptotic cleavage of cellular proteins R-MMU-264870, Caspase-mediated cleavage of cytoskeletal proteins R-MMU-352238, Breakdown of the nuclear lamina |
Miscellaneous databases
BioGRID-ORCSi | 12368, 0 hits in 50 CRISPR screens |
ChiTaRSi | Casp6, mouse |
PROi | PR:O08738 |
RNActi | O08738, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000027997, Expressed in stomach and 277 other tissues |
Genevisiblei | O08738, MM |
Family and domain databases
CDDi | cd00032, CASc, 1 hit |
InterProi | View protein in InterPro IPR029030, Caspase-like_dom_sf IPR037554, Caspase_6 IPR033139, Caspase_cys_AS IPR016129, Caspase_his_AS IPR002398, Pept_C14 IPR002138, Pept_C14_p10 IPR001309, Pept_C14_p20 IPR015917, Pept_C14A |
PANTHERi | PTHR10454, PTHR10454, 1 hit PTHR10454:SF206, PTHR10454:SF206, 1 hit |
PRINTSi | PR00376, IL1BCENZYME |
SMARTi | View protein in SMART SM00115, CASc, 1 hit |
SUPFAMi | SSF52129, SSF52129, 1 hit |
PROSITEi | View protein in PROSITE PS01122, CASPASE_CYS, 1 hit PS01121, CASPASE_HIS, 1 hit PS50207, CASPASE_P10, 1 hit PS50208, CASPASE_P20, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CASP6_MOUSE | |
Accessioni | O08738Primary (citable) accession number: O08738 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | July 1, 1997 | |
Last modified: | February 23, 2022 | |
This is version 181 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families