CASP6

Existing Annotations Review

Gene Description

Existing Annotations Review

Core Functions

CASP6 is an Asp-directed cysteine endopeptidase that cleaves protein substrates after VEHD/VEID-like caspase recognition sequences and can activate its own zymogen by intersubunit-linker self-processing at Asp-193/Asp-179.

CASP6 carries out apoptotic substrate cleavage in intrinsic and executioner-caspase contexts, including RIPK1 cleavage downstream of cytochrome c/caspase-9 and cleavage of nuclear substrates such as lamins and SATB1.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

📄 View Raw YAML

GO Term	Evidence	Action	Reason
GO:0001650 fibrillar center	IDA GO_REF:0000052	UNDECIDED	Summary: The Human Protein Atlas places CASP6 in the fibrillar center, but the local cache has no image-level evidence and the curated CASP6 literature supports broader cytosolic/nuclear pools. Reason: Fibrillar center is a precise nucleolar subcompartment; because the evidence is only the HPA GO_REF row and the local CASP6 literature does not independently support a fibrillar-center pool, retain this for human curator review.
GO:0002218 activation of innate immune response	IDA PMID:32298652 Caspase-6 Is a Key Regulator of Innate Immunity, Inflammasom...	KEEP AS NON CORE	Summary: The influenza-associated CASP6–RIPK3–ZBP1 mechanism in PMID:32298652 is demonstrated in mouse cells and mice; its transfection experiments also use mouse CASP6/RIPK3 constructs. Reason: The influenza-associated CASP6–RIPK3–ZBP1 mechanism in PMID:32298652 is demonstrated in mouse cells and mice; its transfection experiments also use mouse CASP6/RIPK3 constructs. The human claim is retained as a plausible conserved contextual role, not as a directly demonstrated human experiment or a universal inflammasome requirement. Supporting Evidence: PMID:32298652 caspase-6 is able to enhance the interaction between ZBP1 and RIPK3
GO:0004175 endopeptidase activity	IEA GO_REF:0000107	MODIFY	Summary: CASP6 cleaves internal peptide bonds using a catalytic cysteine. Reason: CASP6 cleaves internal peptide bonds using a catalytic cysteine. Asp at the substrate cleavage site specifies recognition, not an aspartic catalytic mechanism. The supported specific activity is cysteine-type endopeptidase activity. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: file:human/CASP6/CASP6-uniprot.txt Belongs to the peptidase C14A family. PMID:32029622 active caspase-6 cleaved purified Bcl2 family protein Bid
GO:0004197 cysteine-type endopeptidase activity	IBA GO_REF:0000033	ACCEPT	Summary: CASP6 is an Asp-directed cysteine endopeptidase; this is its core catalytic activity. Reason: The caspase molecular function is well established by phylogenetic inference, electronic domain mappings, and direct biochemical assays of CASP6 self-processing and substrate cleavage. Supporting Evidence: file:human/CASP6/CASP6-uniprot.txt Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp PMID:7796396 recombinant Mch2 alpha, but not Mch2 beta, possesses protease activity
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:19133298 Self-activation of Caspase-6 in vitro and in vivo: Caspase-6...	ACCEPT	Summary: CASP6 is an Asp-directed cysteine endopeptidase; this is its core catalytic activity. Reason: The caspase molecular function is well established by phylogenetic inference, electronic domain mappings, and direct biochemical assays of CASP6 self-processing and substrate cleavage. Supporting Evidence: PMID:19133298 Casp6 was self-processed and activated in vitro and in vivo PMID:20890311 intramolecular cleavage at Asp 193 is a prerequisite for CASP6 self-activation
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:22858542 Intrinsic cleavage of receptor-interacting protein kinase-1 ...	ACCEPT	Summary: CASP6 is an Asp-directed cysteine endopeptidase; this is its core catalytic activity. Reason: The caspase molecular function is well established by phylogenetic inference, electronic domain mappings, and direct biochemical assays of CASP6 self-processing and substrate cleavage. Supporting Evidence: PMID:22858542 The only apoptotic caspase that cleaved more than 50% of total RIPK1 under these experimental conditions was the executioner caspase-6
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:24904167 Caspase-mediated cleavage of phospholipid flippase for apopt...	ACCEPT	Summary: CASP6 has independently established cysteine-type endopeptidase activity. Reason: CASP6 has independently established cysteine-type endopeptidase activity. The catalytic cysteine and Asp-directed substrate cleavage distinguish caspases from aspartic proteases. A source that does not isolate this activity by itself does not negate the same-target biochemical claim; the original citation remains preserved for provenance. Supporting Evidence: file:human/CASP6/CASP6-uniprot.txt Belongs to the peptidase C14A family. PMID:32029622 active caspase-6 cleaved purified Bcl2 family protein Bid
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:27032039 Reprogramming Caspase-7 Specificity by Regio-Specific Mutati...	ACCEPT	Summary: CASP6 is an Asp-directed cysteine endopeptidase; this is its core catalytic activity. Reason: The caspase molecular function is well established by phylogenetic inference, electronic domain mappings, and direct biochemical assays of CASP6 self-processing and substrate cleavage. Supporting Evidence: PMID:27032039 the global specificity toward natural protein substrates is remarkably similar to that of caspase-6
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:27911442 Palmitoylation of caspase-6 by HIP14 regulates its activatio...	ACCEPT	Summary: CASP6 is an Asp-directed cysteine endopeptidase; this is its core catalytic activity. Reason: The caspase molecular function is well established by phylogenetic inference, electronic domain mappings, and direct biochemical assays of CASP6 self-processing and substrate cleavage. Supporting Evidence: PMID:27911442 the palmitoylation of CASP6 inhibits its activation
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:32029622 An AMPK-caspase-6 axis controls liver damage in nonalcoholic...	ACCEPT	Summary: CASP6 is an Asp-directed cysteine endopeptidase; this is its core catalytic activity. Reason: The caspase molecular function is well established by phylogenetic inference, electronic domain mappings, and direct biochemical assays of CASP6 self-processing and substrate cleavage. Supporting Evidence: PMID:32029622 Active caspase-6 cleaved Bid to induce cytochrome c release, generating a feedforward loop that leads to hepatocyte death.
GO:0004197 cysteine-type endopeptidase activity	IEA GO_REF:0000120	ACCEPT	Summary: CASP6 is an Asp-directed cysteine endopeptidase; this is its core catalytic activity. Reason: The caspase molecular function is well established by phylogenetic inference, electronic domain mappings, and direct biochemical assays of CASP6 self-processing and substrate cleavage. Supporting Evidence: file:human/CASP6/CASP6-uniprot.txt Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp PMID:7796396 recombinant Mch2 alpha, but not Mch2 beta, possesses protease activity
GO:0004197 cysteine-type endopeptidase activity	IMP PMID:22253444 Apoptotic DNA degradation into oligonucleosomal fragments, b...	ACCEPT	Summary: CASP6 has independently established cysteine-type endopeptidase activity. Reason: CASP6 has independently established cysteine-type endopeptidase activity. The catalytic cysteine and Asp-directed substrate cleavage distinguish caspases from aspartic proteases. A source that does not isolate this activity by itself does not negate the same-target biochemical claim; the original citation remains preserved for provenance. Supporting Evidence: file:human/CASP6/CASP6-uniprot.txt Belongs to the peptidase C14A family. PMID:32029622 active caspase-6 cleaved purified Bcl2 family protein Bid
GO:0004197 cysteine-type endopeptidase activity	ISS GO_REF:0000024	ACCEPT	Summary: CASP6 is an Asp-directed cysteine endopeptidase; this is its core catalytic activity. Reason: The caspase molecular function is well established by phylogenetic inference, electronic domain mappings, and direct biochemical assays of CASP6 self-processing and substrate cleavage. Supporting Evidence: file:human/CASP6/CASP6-uniprot.txt Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp PMID:7796396 recombinant Mch2 alpha, but not Mch2 beta, possesses protease activity
GO:0005515 protein binding	IPI PMID:12888622 Caspase cleavage of tau: linking amyloid and neurofibrillary...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The cached MAPT/tau paper supports caspase-dependent tau cleavage but does not establish a CASP6-specific binding function; the bare protein binding term should not be retained. Supporting Evidence: PMID:12888622 Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease.
GO:0005515 protein binding	IPI PMID:18408014 SUMO conjugation to the matrix attachment region-binding pro...	MODIFY	Summary: The SATB1 interaction is a substrate/enzyme context for CASP6 cleavage, not an informative standalone binding activity. Reason: SATB1 is a nuclear substrate whose caspase cleavage is enhanced by sumoylation; the useful CASP6 molecular-function assertion is cysteine-type endopeptidase activity rather than generic protein binding. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:18408014 A SUMO-independent interaction of inactive caspase-6 and SATB1 was noted. Reactome:R-HSA-352268 Cleaved Satb1 dissociates from chromatin
GO:0005515 protein binding	IPI PMID:18723680 Executioner caspase-3 and caspase-7 are functionally distinc...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: CASP6 appears here as a substrate whose activation differs downstream of caspase-3 and caspase-7; the CASP6 side is not a standalone protein-binding activity. Supporting Evidence: PMID:18723680 Differential activity toward multiple substrate proteins, including Bid, XIAP, gelsolin, caspase-6, and cochaperone p23
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a pathway-scale proximity-ligation interaction resource and does not define a CASP6 molecular activity. Supporting Evidence: PMID:25241761 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from the HuRI reference interactome map and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from the HuRI reference interactome map and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from the HuRI reference interactome map and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding is not an informative GO molecular function for CASP6 in this interaction row. Reason: The row comes from a neurodegeneration interactome screen and does not define a CASP6 molecular activity. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.