clpp-1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0009368 endopeptidase Clp complex	IBA GO_REF:0000033	ACCEPT	Summary: CLPP-1 is the proteolytic core of the ClpXP protease complex. The protein forms a homo-oligomeric barrel (two heptameric rings) that assembles with ClpX ATPase to form the functional ATP-dependent protease in the mitochondrial matrix. This annotation is well-supported by phylogenetic inference from characterized ClpP proteins across species. Reason: The IBA annotation correctly identifies CLPP-1 as part of the endopeptidase Clp complex. CLPP-1 assembles as a homo-oligomeric barrel that partners with the AAA+ ATPase ClpX to form the ATP-dependent ClpXP protease. The ClpP proteolytic chamber requires association with ClpX ATPase for substrate recognition and unfolding. Supporting Evidence: file:worm/clpp-1/clpp-1-deep-research-falcon.md clpp-1 encodes the mitochondrial ClpP protease (EC 3.4.21.92), a serine protease of the S14 family that assembles as a homo-oligomeric barrel (typically two heptameric rings) and partners with the AAA+ ATPase ClpX to form the ATP-dependent ClpXP protease in the mitochondrial matrix
GO:0006515 protein quality control for misfolded or incompletely synthesized proteins	IBA GO_REF:0000033	ACCEPT	Summary: CLPP-1, as the proteolytic subunit of the ClpXP complex, degrades misfolded and damaged proteins in the mitochondrial matrix. This represents a core housekeeping function of the protein, providing protein quality control within the mitochondria. Reason: The IBA annotation correctly captures the protein quality control function of CLPP-1. As the proteolytic core of ClpXP, CLPP-1 degrades unfolded or selected proteins that are recognized, unfolded, and translocated by ClpX into the CLPP-1 chamber. Supporting Evidence: file:worm/clpp-1/clpp-1-deep-research-falcon.md CLPP-1 provides processive proteolysis of unfolded or selected proteins that are recognized, unfolded, and translocated by ClpX into the CLPP-1 chamber
GO:0004252 serine-type endopeptidase activity	IBA GO_REF:0000033	ACCEPT	Summary: CLPP-1 is a serine-type endopeptidase belonging to the peptidase S14 family. The protein contains conserved ClpP catalytic motifs with active site serine and histidine residues essential for proteolytic activity (EC 3.4.21.92). Reason: The IBA annotation correctly identifies the serine-type endopeptidase activity of CLPP-1. This is a core molecular function supported by domain architecture (ClpP domain with conserved Ser and His active sites), family membership (peptidase S14), and experimental validation in C. elegans. Supporting Evidence: file:worm/clpp-1/clpp-1-deep-research-falcon.md clpp-1 encodes the mitochondrial ClpP protease (EC 3.4.21.92), a serine protease of the S14 family
GO:0004176 ATP-dependent peptidase activity	IBA GO_REF:0000033	ACCEPT	Summary: CLPP-1 as the proteolytic subunit of the ClpXP complex exhibits ATP-dependent peptidase activity. While CLPP-1 itself does not hydrolyze ATP (that function resides in ClpX), the functional complex requires ATP hydrolysis by ClpX for substrate unfolding and translocation into the CLPP-1 proteolytic chamber. Reason: The IBA annotation is accurate for the ClpXP holoenzyme function. ATP hydrolysis is required for CLPP-1-mediated proteolysis in vivo. In isolated C. elegans mitochondria, ATP-dependent matrix proteolysis is CLPP-dependent and can be inhibited by the ClpP inhibitor LY-CMK. Supporting Evidence: file:worm/clpp-1/clpp-1-deep-research-falcon.md In isolated C. elegans mitochondria, ATP-dependent matrix proteolysis and peptide generation are substantially CLPP-dependent and inhibited by the ClpP inhibitor LY-CMK
GO:0051117 ATPase binding	IBA GO_REF:0000033	ACCEPT	Summary: CLPP-1 binds to the AAA+ ATPase ClpX to form the functional ClpXP protease complex. This interaction is essential for CLPP-1 function as ClpX provides substrate recognition, unfolding, and translocation into the CLPP-1 proteolytic chamber. Reason: The IBA annotation correctly identifies the ATPase binding function of CLPP-1. CLPP-1 partners with ClpX ATPase to form the ATP-dependent ClpXP protease. This is a conserved feature of all ClpP proteases that require AAA+ ATPase partners for substrate delivery. Supporting Evidence: file:worm/clpp-1/clpp-1-deep-research-falcon.md partners with the AAA+ ATPase ClpX to form the ATP-dependent ClpXP protease in the mitochondrial matrix
GO:0004176 ATP-dependent peptidase activity	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation derived from InterPro domain mapping (IPR001907 ClpP domain). This annotation is consistent with the experimentally validated function of CLPP-1 as part of the ATP-dependent ClpXP protease complex. Reason: This IEA annotation is redundant with the IBA annotation for the same term but is acceptable. The InterPro-based inference correctly identifies ATP-dependent peptidase activity based on the conserved ClpP domain.
GO:0004252 serine-type endopeptidase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation from combined automated methods based on InterPro domain and EC number (3.4.21.92). This is consistent with CLPP-1 being a serine protease of the peptidase S14 family with conserved active site serine. Reason: This IEA annotation is redundant with both IBA and IDA annotations for the same term but is acceptable. The automated inference correctly identifies serine-type endopeptidase activity.
GO:0005759 mitochondrial matrix	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation based on UniProtKB subcellular location vocabulary mapping. CLPP-1 localization to the mitochondrial matrix is supported by experimental evidence from mitoplast protection assays and the presence of an N-terminal mitochondrial targeting sequence. Reason: This IEA annotation is redundant with the IDA annotation for the same term but is acceptable. The subcellular location inference correctly identifies mitochondrial matrix localization, which has been experimentally validated.
GO:0006508 proteolysis	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation from combined automated methods. CLPP-1 is involved in proteolysis as the proteolytic subunit of the ClpXP complex, degrading proteins in the mitochondrial matrix. Reason: This IEA annotation is redundant with the IDA annotation for the same term but is acceptable. The term is very general but accurately describes a core function of CLPP-1. More specific terms (serine-type endopeptidase activity, protein quality control) provide additional detail.
GO:0008233 peptidase activity	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation based on UniProtKB keyword mapping (KW-0645 Protease). CLPP-1 has peptidase activity as part of its core function as the proteolytic subunit of the ClpXP complex. Reason: This IEA annotation is very general but accurate. More specific child terms (serine-type endopeptidase activity, ATP-dependent peptidase activity) are also annotated and provide better functional specificity.
GO:0008236 serine-type peptidase activity	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation based on UniProtKB keyword mapping (KW-0720 Serine protease). CLPP-1 is a serine-type peptidase belonging to the peptidase S14 family with conserved active site serine residue. Reason: This IEA annotation is accurate but less specific than the serine-type endopeptidase activity term (GO:0004252) which is also annotated with stronger evidence (IDA, IBA). Both annotations are acceptable.
GO:0016787 hydrolase activity	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation based on UniProtKB keyword mapping (KW-0378 Hydrolase). CLPP-1 has hydrolase activity as it catalyzes the hydrolysis of peptide bonds in protein substrates. Reason: This IEA annotation is very general but technically accurate. CLPP-1 is a hydrolase that cleaves peptide bonds. More specific child terms provide better functional characterization.
GO:0004252 serine-type endopeptidase activity	IDA PMID:17925224 ClpP mediates activation of a mitochondrial unfolded protein...	ACCEPT	Summary: IDA annotation based on direct experimental evidence from Haynes et al. 2007. CLPP-1 was shown to have serine-type endopeptidase activity as the proteolytic subunit of the ClpXP complex in the mitochondrial matrix. The protein belongs to the peptidase S14 family with conserved catalytic residues. Reason: This is a core molecular function annotation with direct experimental support. CLPP-1 encodes a mitochondrial matrix protease homologous to bacterial ClpP, which is a well-characterized serine protease. Supporting Evidence: PMID:17925224 clpp-1, which encodes a mitochondrial matrix protease homologous to bacterial ClpP
GO:0006508 proteolysis	IDA PMID:17925224 ClpP mediates activation of a mitochondrial unfolded protein...	ACCEPT	Summary: IDA annotation based on direct experimental evidence from Haynes et al. 2007. CLPP-1 is involved in proteolysis as the proteolytic subunit of the ClpXP complex, degrading proteins in the mitochondrial matrix. Reason: This annotation is accurate but general. The term proteolysis is a broad biological process term. More specific annotations (protein quality control, UPR-mt) provide better functional context. Supporting Evidence: PMID:17925224 clpp-1, which encodes a mitochondrial matrix protease homologous to bacterial ClpP
GO:0034514 mitochondrial unfolded protein response	IMP PMID:17925224 ClpP mediates activation of a mitochondrial unfolded protein...	ACCEPT	Summary: IMP annotation based on mutant phenotype analysis from Haynes et al. 2007. clpp-1(RNAi) attenuates UPR-mt activation, blocking DVE-1 nuclear redistribution and induction of mitochondrial chaperone genes. CLPP-1 acts upstream to generate peptide signals that are exported via HAF-1 to activate nuclear transcription factors. Reason: This is a core biological process annotation with strong experimental support. CLPP-1 is required for signaling the mitochondrial unfolded protein response. This represents a key function beyond simple housekeeping proteolysis - CLPP-1 generates signaling peptides that communicate mitochondrial stress to the nucleus. Supporting Evidence: PMID:17925224 These events and the downstream UPR(mt) are attenuated in animals with reduced activity of clpp-1, which encodes a mitochondrial matrix protease homologous to bacterial ClpP
GO:0005759 mitochondrial matrix	IDA PMID:17925224 ClpP mediates activation of a mitochondrial unfolded protein...	ACCEPT	Summary: IDA annotation based on direct localization evidence from Haynes et al. 2007. CLPP-1 was shown to localize to the mitochondrial matrix using mitoplast protection assays. The protein contains an N-terminal mitochondrial targeting sequence (residues 1-25) that directs import into the matrix. Reason: This is a well-supported cellular component annotation. CLPP-1 localization to the mitochondrial matrix is consistent with its function in the ClpXP protease complex that degrades matrix proteins and generates UPR-mt signals. Supporting Evidence: PMID:17925224 clpp-1, which encodes a mitochondrial matrix protease homologous to bacterial ClpP file:worm/clpp-1/clpp-1-deep-research-falcon.md CLPP-1 resides in the mitochondrial matrix; epitope-tagged CLPP-1 fractionates with mitochondrial pellets and is protected from exogenous protease in mitoplasts, consistent with matrix localization