STUB1 (E3 ubiquitin-protein ligase CHIP, C-terminus of HSC70-interacting protein) is a cytoplasmic protein that couples the molecular-chaperone and ubiquitin-proteasome systems. It has a bipartite architecture: an N-terminal tetratricopeptide repeat (TPR) domain that binds the C-terminal EEVD/MEEVD motifs of HSP70/HSC70 and HSP90, and a C-terminal U-box domain that confers RING-type E3 ubiquitin-ligase activity. Acting as a chaperone-associated 'triage' factor, CHIP ubiquitinates chaperone-bound misfolded or damaged client proteins (in cooperation with E2 enzymes such as UBE2D and UBE2N/UBE2V1) and targets them for proteasomal degradation, while also modulating the activity of the HSP70/HSC70/HSP90 chaperone cycle as a co-chaperone. CHIP functions as a homodimer and additionally participates in protein quality control, ERAD, chaperone-mediated autophagy and mitophagy, and the regulated turnover of numerous specific substrates (e.g. tau, FOXO1, NOS1, POLB, ESR1). Loss of CHIP ubiquitin-ligase activity causes autosomal-recessive (SCAR16) and autosomal-dominant (SCA48) spinocerebellar ataxia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0045862 positive regulation of proteolysis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: positive regulation of proteolysis is a downstream process of CHIP's ubiquitin-ligase / quality-control activity. Reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0000209 protein polyubiquitination | IBA GO_REF:0000033 | ACCEPT | Summary: protein polyubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | IBA GO_REF:0000033 | ACCEPT | Summary: CHIP performs protein quality control by ubiquitinating misfolded chaperone clients for degradation. Reason: Central CHIP function: triage of misfolded chaperone substrates to the proteasome. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0030018 Z disc | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Z disc: specialized localization (Z-disc / nuclear inclusion body) in particular contexts. Reason: Context-specific localization; peripheral to CHIP's principal cytoplasmic QC role. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0071218 cellular response to misfolded protein | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: cellular response to misfolded protein: CHIP participates in cellular stress/misfolded-protein responses via its triage activity. Reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CHIP translocates to the nucleus under some conditions; nuclear pool is documented but secondary. Reason: UniProt lists Nucleus (translocates to the nucleus); non-core relative to the cytoplasmic function. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt Translocates to the nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CHIP localizes to mitochondria, linked to mitochondrial QC/mitophagy. Reason: UniProt lists Mitochondrion (by similarity); a specialized non-core localization. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt Mitochondrion |
| GO:0007165 signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: signal transduction: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000120 | ACCEPT | Summary: protein ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0030163 protein catabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: protein catabolic process is a downstream process of CHIP's ubiquitin-ligase / quality-control activity. Reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0033554 cellular response to stress | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: cellular response to stress: CHIP participates in cellular stress/misfolded-protein responses via its triage activity. Reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000120 | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005515 protein binding | IPI PMID:16275660 Identification of VCP/p97, carboxyl terminus of Hsp70-intera... | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as heat shock protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as heat shock protein binding, a core co-chaperone function. Proposed replacements: heat shock protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:16293251 CHIP interacts with heat shock factor 1 during heat stress. | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as heat shock protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as heat shock protein binding, a core co-chaperone function. Proposed replacements: heat shock protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:16307917 Chaperoned ubiquitylation--crystal structures of the CHIP U ... | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp90 protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as Hsp90 protein binding, a core co-chaperone function. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:19875381 A proteomic investigation of ligand-dependent HSP90 complexe... | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp90 protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as Hsp90 protein binding, a core co-chaperone function. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:20029029 Regulation of epidermal growth factor receptor trafficking b... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:20588253 CHIP-dependent termination of MEKK2 regulates temporal ERK a... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:20618441 CHIP participates in protein triage decisions by preferentia... | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as heat shock protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as heat shock protein binding, a core co-chaperone function. Proposed replacements: heat shock protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:21358815 Ubiquitinylation of Ξ±-synuclein by carboxyl terminus Hsp70-i... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:21360678 Label-free quantitative proteomics and SAINT analysis enable... | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp90 protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as Hsp90 protein binding, a core co-chaperone function. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:22190034 Global landscape of HIV-human protein complexes. | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:23973223 The ubiquitin ligase Stub1 negatively modulates regulatory T... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:24510904 Unbiased screen for interactors of leucine-rich repeat kinas... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp90 protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as Hsp90 protein binding, a core co-chaperone function. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:25260751 The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in respon... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:25277244 The functional landscape of Hsp27 reveals new cellular proce... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:29513927 Comparative Protein Interaction Network Analysis Identifies ... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive... | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp70 protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as Hsp70 protein binding, a core co-chaperone function. Proposed replacements: Hsp70 protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:31046837 Parkinson's disease-associated LRRK2-G2019S mutant acts thro... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp70 protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as Hsp70 protein binding, a core co-chaperone function. Proposed replacements: Hsp70 protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:35266954 The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its loc... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0000165 MAPK cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MAPK cascade: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0002931 response to ischemia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: response to ischemia: CHIP participates in cellular stress/misfolded-protein responses via its triage activity. Reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0006511 ubiquitin-dependent protein catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | IEA GO_REF:0000107 | ACCEPT | Summary: CHIP performs protein quality control by ubiquitinating misfolded chaperone clients for degradation. Reason: Central CHIP function: triage of misfolded chaperone substrates to the proteasome. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0010614 negative regulation of cardiac muscle hypertrophy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: negative regulation of cardiac muscle hypertrophy: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0030018 Z disc | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Z disc: specialized localization (Z-disc / nuclear inclusion body) in particular contexts. Reason: Context-specific localization; peripheral to CHIP's principal cytoplasmic QC role. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0030968 endoplasmic reticulum unfolded protein response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: endoplasmic reticulum unfolded protein response: CHIP participates in cellular stress/misfolded-protein responses via its triage activity. Reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0031398 positive regulation of protein ubiquitination | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: positive regulation of protein ubiquitination is a downstream process of CHIP's ubiquitin-ligase / quality-control activity. Reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ubiquitin protein ligase binding: a specific partner/substrate-binding annotation for CHIP. Reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0034392 negative regulation of smooth muscle cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: negative regulation of smooth muscle cell apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0034393 positive regulation of smooth muscle cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: positive regulation of smooth muscle cell apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0034450 ubiquitin-ubiquitin ligase activity | IEA GO_REF:0000107 | ACCEPT | Summary: CHIP elongates ubiquitin chains on substrates (ubiquitin-ubiquitin ligase / E4-like activity), consistent with its polyubiquitination role. Reason: Supported by CHIP's documented polyubiquitination of chaperone clients and chain elongation activity. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0034605 cellular response to heat | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cellular response to heat: CHIP participates in cellular stress/misfolded-protein responses via its triage activity. Reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0035359 negative regulation of peroxisome proliferator activated receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: negative regulation of peroxisome proliferator activated receptor signaling pathway: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000107 | ACCEPT | Summary: CHIP forms a homodimer, required for its E3 ligase activity. Reason: CHIP functions as a homodimer; homodimerization is a genuine, specific molecular feature. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: negative regulation of apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0051087 protein-folding chaperone binding | IEA GO_REF:0000107 | ACCEPT | Summary: CHIP binds the folding chaperones HSP70/HSC70/HSP90, consistent with its co-chaperone role. Reason: Supported by UniProt FUNCTION; chaperone binding underpins CHIP's substrate-triage activity. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0061684 chaperone-mediated autophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: chaperone-mediated autophagy: CHIP modulates chaperone-mediated autophagy/mitophagy and chaperone complex assembly. Reason: Documented co-chaperone-linked process; non-core relative to CHIP's E3-ligase and chaperone-binding MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0071218 cellular response to misfolded protein | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cellular response to misfolded protein: CHIP participates in cellular stress/misfolded-protein responses via its triage activity. Reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cellular response to hypoxia: CHIP participates in cellular stress/misfolded-protein responses via its triage activity. Reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:1901526 positive regulation of mitophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: positive regulation of mitophagy: CHIP modulates chaperone-mediated autophagy/mitophagy and chaperone complex assembly. Reason: Documented co-chaperone-linked process; non-core relative to CHIP's E3-ligase and chaperone-binding MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:1904694 negative regulation of vascular associated smooth muscle contraction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: negative regulation of vascular associated smooth muscle contraction: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | TAS Reactome:R-HSA-2173788 | KEEP AS NON CORE | Summary: negative regulation of transforming growth factor beta receptor signaling pathway: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0038128 ERBB2 signaling pathway | TAS Reactome:R-HSA-1227986 | KEEP AS NON CORE | Summary: ERBB2 signaling pathway: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | TAS Reactome:R-HSA-6807134 | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | TAS Reactome:R-HSA-9009308 | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: CHIP translocates to the nucleus under some conditions; nuclear pool is documented but secondary. Reason: UniProt lists Nucleus (translocates to the nucleus); non-core relative to the cytoplasmic function. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt Translocates to the nucleus |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:17369820 The ubiquitin-selective chaperone CDC-48/p97 links myosin as... | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:23973223 The ubiquitin ligase Stub1 negatively modulates regulatory T... | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CHIP localizes to mitochondria, linked to mitochondrial QC/mitophagy. Reason: UniProt lists Mitochondrion (by similarity); a specialized non-core localization. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt Mitochondrion |
| GO:0061630 ubiquitin protein ligase activity | EXP PMID:11557750 CHIP is a U-box-dependent E3 ubiquitin ligase: identificatio... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | EXP PMID:15466472 Ubiquitylation of neuronal nitric-oxide synthase by CHIP, a ... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0002931 response to ischemia | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: response to ischemia: CHIP participates in cellular stress/misfolded-protein responses via its triage activity. Reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CHIP translocates to the nucleus under some conditions; nuclear pool is documented but secondary. Reason: UniProt lists Nucleus (translocates to the nucleus); non-core relative to the cytoplasmic function. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt Translocates to the nucleus |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0034605 cellular response to heat | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: cellular response to heat: CHIP participates in cellular stress/misfolded-protein responses via its triage activity. Reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0071456 cellular response to hypoxia | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: cellular response to hypoxia: CHIP participates in cellular stress/misfolded-protein responses via its triage activity. Reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0035359 negative regulation of peroxisome proliferator activated receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: negative regulation of peroxisome proliferator activated receptor signaling pathway: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:19713937 Ubiquitin ligase ARF-BP1/Mule modulates base excision repair... | ACCEPT | Summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-1918092 | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-2187368 | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0006511 ubiquitin-dependent protein catabolic process | IMP PMID:23990462 Endoplasmic reticulum protein quality control is determined ... | ACCEPT | Summary: ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0036503 ERAD pathway | IMP PMID:23990462 Endoplasmic reticulum protein quality control is determined ... | KEEP AS NON CORE | Summary: ERAD pathway is a downstream process of CHIP's ubiquitin-ligase / quality-control activity. Reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0034393 positive regulation of smooth muscle cell apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: positive regulation of smooth muscle cell apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0000165 MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: MAPK cascade: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005515 protein binding | IPI PMID:19483080 C terminus of Hsc70-interacting protein promotes smooth musc... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:20724525 Novel role of C terminus of Hsc70-interacting protein (CHIP)... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0034392 negative regulation of smooth muscle cell apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: negative regulation of smooth muscle cell apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0034392 negative regulation of smooth muscle cell apoptotic process | IMP PMID:20724525 Novel role of C terminus of Hsc70-interacting protein (CHIP)... | KEEP AS NON CORE | Summary: negative regulation of smooth muscle cell apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:1901526 positive regulation of mitophagy | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: positive regulation of mitophagy: CHIP modulates chaperone-mediated autophagy/mitophagy and chaperone complex assembly. Reason: Documented co-chaperone-linked process; non-core relative to CHIP's E3-ligase and chaperone-binding MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0045862 positive regulation of proteolysis | IMP PMID:26634371 Structural studies of UBXN2A and mortalin interaction and th... | KEEP AS NON CORE | Summary: positive regulation of proteolysis is a downstream process of CHIP's ubiquitin-ligase / quality-control activity. Reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005515 protein binding | IPI PMID:26265139 UBXN2A regulates nicotinic receptor degradation by modulatin... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:26265139 UBXN2A regulates nicotinic receptor degradation by modulatin... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:1904294 positive regulation of ERAD pathway | IMP PMID:26265139 UBXN2A regulates nicotinic receptor degradation by modulatin... | KEEP AS NON CORE | Summary: positive regulation of ERAD pathway is a downstream process of CHIP's ubiquitin-ligase / quality-control activity. Reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | IMP PMID:15781469 CHIP controls the sensitivity of transforming growth factor-... | KEEP AS NON CORE | Summary: negative regulation of transforming growth factor beta receptor signaling pathway: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:15781469 CHIP controls the sensitivity of transforming growth factor-... | ACCEPT | Summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | IMP PMID:15781469 CHIP controls the sensitivity of transforming growth factor-... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0070412 R-SMAD binding | IPI PMID:15781469 CHIP controls the sensitivity of transforming growth factor-... | KEEP AS NON CORE | Summary: R-SMAD binding: a specific partner/substrate-binding annotation for CHIP. Reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0042803 protein homodimerization activity | IPI PMID:23990462 Endoplasmic reticulum protein quality control is determined ... | ACCEPT | Summary: CHIP forms a homodimer, required for its E3 ligase activity. Reason: CHIP functions as a homodimer; homodimerization is a genuine, specific molecular feature. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0042803 protein homodimerization activity | ISS GO_REF:0000024 | ACCEPT | Summary: CHIP forms a homodimer, required for its E3 ligase activity. Reason: CHIP functions as a homodimer; homodimerization is a genuine, specific molecular feature. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:24043303 The ubiquitin ligase CHIP prevents SirT6 degradation through... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005634 nucleus | IDA PMID:23973223 The ubiquitin ligase Stub1 negatively modulates regulatory T... | KEEP AS NON CORE | Summary: CHIP translocates to the nucleus under some conditions; nuclear pool is documented but secondary. Reason: UniProt lists Nucleus (translocates to the nucleus); non-core relative to the cytoplasmic function. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt Translocates to the nucleus |
| GO:0006513 protein monoubiquitination | IDA PMID:24043303 The ubiquitin ligase CHIP prevents SirT6 degradation through... | ACCEPT | Summary: protein monoubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0050821 protein stabilization | IDA PMID:24043303 The ubiquitin ligase CHIP prevents SirT6 degradation through... | KEEP AS NON CORE | Summary: protein stabilization is a downstream process of CHIP's ubiquitin-ligase / quality-control activity. Reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0048156 tau protein binding | NAS PMID:28386764 Roles of tau protein in health and disease. | KEEP AS NON CORE | Summary: CHIP binds tau (MAPT), a chaperone client it ubiquitinates. Reason: Real substrate interaction (tau); informative but a specific client-binding annotation, non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005515 protein binding | IPI PMID:29883609 PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylat... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0016567 protein ubiquitination | IMP PMID:29883609 PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylat... | ACCEPT | Summary: protein ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IMP PMID:29883609 PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylat... | ACCEPT | Summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | IMP PMID:23990462 Endoplasmic reticulum protein quality control is determined ... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0016567 protein ubiquitination | IDA PMID:14610072 Dimerization of the human E3 ligase CHIP via a coiled-coil d... | ACCEPT | Summary: protein ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:14610072 Dimerization of the human E3 ligase CHIP via a coiled-coil d... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005515 protein binding | IPI PMID:16207813 BAG-2 acts as an inhibitor of the chaperone-associated ubiqu... | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp70 protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as Hsp70 protein binding, a core co-chaperone function. Proposed replacements: Hsp70 protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0031072 heat shock protein binding | IPI PMID:16207813 BAG-2 acts as an inhibitor of the chaperone-associated ubiqu... | ACCEPT | Summary: CHIP binds heat shock proteins (HSP70/HSC70/HSP90) through its TPR domain. Reason: Supported by UniProt FUNCTION; binding HSP70/HSP90 chaperones is central to CHIP's triage role. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0051087 protein-folding chaperone binding | IPI PMID:16207813 BAG-2 acts as an inhibitor of the chaperone-associated ubiqu... | ACCEPT | Summary: CHIP binds the folding chaperones HSP70/HSC70/HSP90, consistent with its co-chaperone role. Reason: Supported by UniProt FUNCTION; chaperone binding underpins CHIP's substrate-triage activity. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0061630 ubiquitin protein ligase activity | IGI PMID:16207813 BAG-2 acts as an inhibitor of the chaperone-associated ubiqu... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0101031 protein folding chaperone complex | IPI PMID:16207813 BAG-2 acts as an inhibitor of the chaperone-associated ubiqu... | KEEP AS NON CORE | Summary: CHIP associates with HSP70/HSP90 chaperone complexes as a co-chaperone. Reason: CHIP partners with the folding-chaperone machinery; a reasonable complex annotation, non-core relative to its ligase/co-chaperone MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0006511 ubiquitin-dependent protein catabolic process | ISS PMID:18292230 Akt and CHIP coregulate tau degradation through coordinated ... | ACCEPT | Summary: ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0006511 ubiquitin-dependent protein catabolic process | IGI PMID:18292230 Akt and CHIP coregulate tau degradation through coordinated ... | ACCEPT | Summary: ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | TAS PMID:19953350 Brain distribution of carboxy terminus of Hsc70-interacting ... | ACCEPT | Summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005515 protein binding | IPI PMID:27708256 ARD1-mediated Hsp70 acetylation balances stress-induced prot... | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as heat shock protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as heat shock protein binding, a core co-chaperone function. Proposed replacements: heat shock protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:24613385 Hsp70 and Hsp90 oppositely regulate TGF-Ξ² signaling through ... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | IMP PMID:24613385 Hsp70 and Hsp90 oppositely regulate TGF-Ξ² signaling through ... | KEEP AS NON CORE | Summary: negative regulation of transforming growth factor beta receptor signaling pathway: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0030544 Hsp70 protein binding | IPI PMID:24613385 Hsp70 and Hsp90 oppositely regulate TGF-Ξ² signaling through ... | ACCEPT | Summary: CHIP binds HSP70/HSC70 via its TPR domain; Hsp70 protein binding is a core co-chaperone molecular function. Reason: Supported by UniProt FUNCTION (modulates Hsp70/Hsc70/Hsp90) and the TPR-domain HSP70-binding role of CHIP. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:24613385 Hsp70 and Hsp90 oppositely regulate TGF-Ξ² signaling through ... | ACCEPT | Summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0046332 SMAD binding | IPI PMID:24613385 Hsp70 and Hsp90 oppositely regulate TGF-Ξ² signaling through ... | KEEP AS NON CORE | Summary: SMAD binding: a specific partner/substrate-binding annotation for CHIP. Reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:24613385 Hsp70 and Hsp90 oppositely regulate TGF-Ξ² signaling through ... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005515 protein binding | IPI PMID:23431407 Distinct roles of molecular chaperones HSP90Ξ± and HSP90Ξ² in ... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005515 protein binding | IPI PMID:27353360 The FNIP co-chaperones decelerate the Hsp90 chaperone cycle ... | MODIFY | Summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp90 protein binding. Reason: The WITH partner is an HSP70/HSP90-family chaperone; CHIP's binding is precisely captured as Hsp90 protein binding, a core co-chaperone function. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:16809764 Histone deacetylase 8 safeguards the human ever-shorter telo... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0016567 protein ubiquitination | IDA PMID:16809764 Histone deacetylase 8 safeguards the human ever-shorter telo... | ACCEPT | Summary: protein ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0016567 protein ubiquitination | IMP PMID:16809764 Histone deacetylase 8 safeguards the human ever-shorter telo... | ACCEPT | Summary: protein ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0031647 regulation of protein stability | IDA PMID:16809764 Histone deacetylase 8 safeguards the human ever-shorter telo... | KEEP AS NON CORE | Summary: regulation of protein stability is a downstream process of CHIP's ubiquitin-ligase / quality-control activity. Reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:16809764 Histone deacetylase 8 safeguards the human ever-shorter telo... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | IMP PMID:16809764 Histone deacetylase 8 safeguards the human ever-shorter telo... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0030544 Hsp70 protein binding | IDA PMID:23990462 Endoplasmic reticulum protein quality control is determined ... | ACCEPT | Summary: CHIP binds HSP70/HSC70 via its TPR domain; Hsp70 protein binding is a core co-chaperone molecular function. Reason: Supported by UniProt FUNCTION (modulates Hsp70/Hsc70/Hsp90) and the TPR-domain HSP70-binding role of CHIP. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:16275660 Identification of VCP/p97, carboxyl terminus of Hsp70-intera... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:19103148 CYP3A4 ubiquitination by gp78 (the tumor autocrine motility ... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0000151 ubiquitin ligase complex | IDA PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | ACCEPT | Summary: CHIP functions within ubiquitin ligase complexes (with E2 enzymes and chaperones). Reason: Consistent with CHIP's E3 ligase activity acting in complex with E2s and chaperone-bound substrates. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0001664 G protein-coupled receptor binding | IPI PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | KEEP AS NON CORE | Summary: G protein-coupled receptor binding: a specific partner/substrate-binding annotation for CHIP. Reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005783 endoplasmic reticulum | IDA PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | KEEP AS NON CORE | Summary: CHIP participates in ER-associated degradation (ERAD) of certain substrates. Reason: ER context reflects CHIP's ERAD role (e.g. CHRNA3, CYP3A4); non-core localization. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | KEEP AS NON CORE | Summary: ubiquitin protein ligase binding: a specific partner/substrate-binding annotation for CHIP. Reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0000151 ubiquitin ligase complex | IDA PMID:16275660 Identification of VCP/p97, carboxyl terminus of Hsp70-intera... | ACCEPT | Summary: CHIP functions within ubiquitin ligase complexes (with E2 enzymes and chaperones). Reason: Consistent with CHIP's E3 ligase activity acting in complex with E2s and chaperone-bound substrates. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0000209 protein polyubiquitination | IDA PMID:16275660 Identification of VCP/p97, carboxyl terminus of Hsp70-intera... | ACCEPT | Summary: protein polyubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1918092 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2187368 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2187375 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6807134 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9009308 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9009309 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9688831 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9688838 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9796368 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9796387 | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005515 protein binding | IPI PMID:22366786 Mutations affecting the cytoplasmic functions of the co-chap... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0000151 ubiquitin ligase complex | IDA PMID:16307917 Chaperoned ubiquitylation--crystal structures of the CHIP U ... | ACCEPT | Summary: CHIP functions within ubiquitin ligase complexes (with E2 enzymes and chaperones). Reason: Consistent with CHIP's E3 ligase activity acting in complex with E2s and chaperone-bound substrates. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0051865 protein autoubiquitination | IDA PMID:16307917 Chaperoned ubiquitylation--crystal structures of the CHIP U ... | ACCEPT | Summary: protein autoubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:16307917 Chaperoned ubiquitylation--crystal structures of the CHIP U ... | ACCEPT | Summary: protein K63-linked ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0000209 protein polyubiquitination | IMP PMID:19713937 Ubiquitin ligase ARF-BP1/Mule modulates base excision repair... | ACCEPT | Summary: protein polyubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0004842 ubiquitin-protein transferase activity | IMP PMID:19713937 Ubiquitin ligase ARF-BP1/Mule modulates base excision repair... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0006511 ubiquitin-dependent protein catabolic process | IMP PMID:19713937 Ubiquitin ligase ARF-BP1/Mule modulates base excision repair... | ACCEPT | Summary: ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005515 protein binding | IPI PMID:19423554 Functional interaction of DYX1C1 with estrogen receptors sug... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:15466472 Ubiquitylation of neuronal nitric-oxide synthase by CHIP, a ... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0051865 protein autoubiquitination | IDA PMID:18042044 Two different classes of E2 ubiquitin-conjugating enzymes ar... | ACCEPT | Summary: protein autoubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0019900 kinase binding | IPI PMID:17512523 Parkin interacts with LIM Kinase 1 and reduces its cofilin-p... | KEEP AS NON CORE | Summary: kinase binding: a specific partner/substrate-binding annotation for CHIP. Reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005737 cytoplasm | IDA PMID:16831871 CHIP protects from the neurotoxicity of expanded and wild-ty... | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | IDA PMID:16831871 CHIP protects from the neurotoxicity of expanded and wild-ty... | ACCEPT | Summary: CHIP performs protein quality control by ubiquitinating misfolded chaperone clients for degradation. Reason: Central CHIP function: triage of misfolded chaperone substrates to the proteasome. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0031398 positive regulation of protein ubiquitination | IDA PMID:16831871 CHIP protects from the neurotoxicity of expanded and wild-ty... | KEEP AS NON CORE | Summary: positive regulation of protein ubiquitination is a downstream process of CHIP's ubiquitin-ligase / quality-control activity. Reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0042405 nuclear inclusion body | IDA PMID:16831871 CHIP protects from the neurotoxicity of expanded and wild-ty... | KEEP AS NON CORE | Summary: nuclear inclusion body: specialized localization (Z-disc / nuclear inclusion body) in particular contexts. Reason: Context-specific localization; peripheral to CHIP's principal cytoplasmic QC role. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0051787 misfolded protein binding | IDA PMID:16831871 CHIP protects from the neurotoxicity of expanded and wild-ty... | ACCEPT | Summary: CHIP recognizes misfolded chaperone-bound clients for ubiquitination. Reason: Supported by UniProt FUNCTION (targets misfolded chaperone substrates); misfolded protein binding underlies substrate selection. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0071218 cellular response to misfolded protein | IDA PMID:16831871 CHIP protects from the neurotoxicity of expanded and wild-ty... | KEEP AS NON CORE | Summary: cellular response to misfolded protein: CHIP participates in cellular stress/misfolded-protein responses via its triage activity. Reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0090035 positive regulation of chaperone-mediated protein complex assembly | IDA PMID:16831871 CHIP protects from the neurotoxicity of expanded and wild-ty... | KEEP AS NON CORE | Summary: positive regulation of chaperone-mediated protein complex assembly: CHIP modulates chaperone-mediated autophagy/mitophagy and chaperone complex assembly. Reason: Documented co-chaperone-linked process; non-core relative to CHIP's E3-ligase and chaperone-binding MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0051879 Hsp90 protein binding | IDA PMID:11146632 The co-chaperone CHIP regulates protein triage decisions med... | ACCEPT | Summary: CHIP binds HSP90 via its TPR domain; Hsp90 protein binding is a core co-chaperone molecular function. Reason: Supported by UniProt FUNCTION (modulates Hsp70/Hsc70/Hsp90); CHIP is a TPR co-chaperone of HSP90. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0034450 ubiquitin-ubiquitin ligase activity | ISS GO_REF:0000024 | ACCEPT | Summary: CHIP elongates ubiquitin chains on substrates (ubiquitin-ubiquitin ligase / E4-like activity), consistent with its polyubiquitination role. Reason: Supported by CHIP's documented polyubiquitination of chaperone clients and chain elongation activity. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0019899 enzyme binding | IPI PMID:16280320 DPM1, the catalytic subunit of dolichol-phosphate mannose sy... | KEEP AS NON CORE | Summary: enzyme binding: a specific partner/substrate-binding annotation for CHIP. Reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0005515 protein binding | IPI PMID:11146632 The co-chaperone CHIP regulates protein triage decisions med... | KEEP AS NON CORE | Summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative. Reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core. Supporting Evidence: file:human/STUB1/STUB1-goa.tsv GO:0005515 protein binding |
| GO:0005737 cytoplasm | IDA PMID:10330192 Identification of CHIP, a novel tetratricopeptide repeat-con... | ACCEPT | Summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients. Reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0030544 Hsp70 protein binding | IDA PMID:10330192 Identification of CHIP, a novel tetratricopeptide repeat-con... | ACCEPT | Summary: CHIP binds HSP70/HSC70 via its TPR domain; Hsp70 protein binding is a core co-chaperone molecular function. Reason: Supported by UniProt FUNCTION (modulates Hsp70/Hsc70/Hsp90) and the TPR-domain HSP70-binding role of CHIP. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt chaperone complexes, including Hsp70, Hsc70 and Hsp90 |
| GO:0030911 TPR domain binding | IDA PMID:11146632 The co-chaperone CHIP regulates protein triage decisions med... | KEEP AS NON CORE | Summary: CHIP's TPR domain mediates chaperone binding; this annotation reflects TPR-mediated interactions. Reason: Real TPR-mediated interaction property; captured more informatively by the Hsp70/Hsp90 binding terms. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt The TPR domain is essential for ubiquitination mediated by |
| GO:0031398 positive regulation of protein ubiquitination | IDA PMID:11146632 The co-chaperone CHIP regulates protein triage decisions med... | KEEP AS NON CORE | Summary: positive regulation of protein ubiquitination is a downstream process of CHIP's ubiquitin-ligase / quality-control activity. Reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0031943 regulation of glucocorticoid metabolic process | IDA PMID:11146632 The co-chaperone CHIP regulates protein triage decisions med... | KEEP AS NON CORE | Summary: regulation of glucocorticoid metabolic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client. Reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IDA PMID:11146632 The co-chaperone CHIP regulates protein triage decisions med... | KEEP AS NON CORE | Summary: positive regulation of proteasomal ubiquitin-dependent protein catabolic process is a downstream process of CHIP's ubiquitin-ligase / quality-control activity. Reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0030674 protein-macromolecule adaptor activity | TAS PMID:16307917 Chaperoned ubiquitylation--crystal structures of the CHIP U ... | KEEP AS NON CORE | Summary: protein-macromolecule adaptor activity: a specific partner/substrate-binding annotation for CHIP. Reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0000209 protein polyubiquitination | IDA PMID:15781469 CHIP controls the sensitivity of transforming growth factor-... | ACCEPT | Summary: protein polyubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates. Reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase). Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0004842 ubiquitin-protein transferase activity | TAS PMID:16307917 Chaperoned ubiquitylation--crystal structures of the CHIP U ... | ACCEPT | Summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function. Reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
| GO:0031371 ubiquitin conjugating enzyme complex | TAS PMID:16307917 Chaperoned ubiquitylation--crystal structures of the CHIP U ... | KEEP AS NON CORE | Summary: CHIP acts together with E2 ubiquitin-conjugating enzymes (e.g. UBE2N/UBE2D). Reason: Reflects CHIP-E2 cooperation; non-core relative to its E3 ligase MF. Supporting Evidence: file:human/STUB1/STUB1-uniprot.txt E3 ubiquitin-protein ligase which targets misfolded chaperone |
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Download this section (compressed HTML)Q: How does CHIP discriminate between chaperone clients destined for refolding versus ubiquitination/degradation, and which features of the chaperone-client complex bias this triage decision?
Q: How do the SCAR16 (recessive) and SCA48 (dominant) STUB1 variants differ mechanistically (loss of ligase activity, loss of dimerization, or dominant-negative effects on the chaperone-ligase axis)?
Q: To what extent are CHIP's many substrate-specific physiological roles (cardiac, immune, vascular) driven by tissue-specific chaperone/co-chaperone context versus intrinsic substrate selectivity?
Experiment: Reconstitute CHIP-mediated ubiquitination in vitro with HSP70/HSP90-bound model clients and defined E2s to dissect how TPR-domain chaperone binding and U-box catalysis are coordinated, using TPR and U-box point mutants.
Experiment: Compare client/substrate profiles (ubiquitinome and stability proteomics) in CHIP-knockout versus SCAR16/SCA48 patient-variant knock-in cells to map disease-relevant substrate dysregulation.
Experiment: Quantify CHIP homodimerization and its requirement for E3 activity using engineered monomeric variants, correlating with chaperone binding and substrate turnover.
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