STUB1

UniProt ID: Q9UNE7
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

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.

Existing Annotations Review

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 α-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-β 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-β 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-β 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-β 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-β 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-β 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 HSP90α and HSP90β 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

Core Functions

U-box-type E3 ubiquitin-protein ligase that, in cooperation with E2 enzymes, ubiquitinates chaperone-bound misfolded/damaged client proteins and targets them for proteasomal degradation.

Molecular Function:
ubiquitin protein ligase activity
Cellular Locations:
cytosol
Supporting Evidence:
  • file:human/STUB1/STUB1-uniprot.txt
    E3 ubiquitin-protein ligase which targets misfolded chaperone

HSP70/HSC70/HSP90 co-chaperone: via its TPR domain CHIP binds these chaperones and modulates their activity, coupling client triage to the chaperone cycle.

Molecular Function:
Hsp70 protein binding
Cellular Locations:
cytosol
Supporting Evidence:
  • file:human/STUB1/STUB1-uniprot.txt
    chaperone complexes, including Hsp70, Hsc70 and Hsp90

Protein quality control: CHIP recognizes misfolded chaperone substrates and routes them to ubiquitin-dependent proteasomal degradation, integrating folding and degradation decisions.

Molecular Function:
ubiquitin-protein transferase activity
Cellular Locations:
cytosol
Supporting Evidence:
  • file:human/STUB1/STUB1-uniprot.txt
    E3 ubiquitin-protein ligase which targets misfolded chaperone

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs using sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs by Ensembl Compara
GO_REF:0000117
Electronic GO annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10330192
Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions.
PMID:11146632
The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins.
PMID:11557750
CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation.
PMID:12150907
CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity.
PMID:14610072
Dimerization of the human E3 ligase CHIP via a coiled-coil domain is essential for its activity.
PMID:15466472
Ubiquitylation of neuronal nitric-oxide synthase by CHIP, a chaperone-dependent E3 ligase.
PMID:15781469
CHIP controls the sensitivity of transforming growth factor-beta signaling by modulating the basal level of Smad3 through ubiquitin-mediated degradation.
PMID:16207813
BAG-2 acts as an inhibitor of the chaperone-associated ubiquitin ligase CHIP.
PMID:16275660
Identification of VCP/p97, carboxyl terminus of Hsp70-interacting protein (CHIP), and amphiphysin II interaction partners using membrane-based human proteome arrays.
PMID:16280320
DPM1, the catalytic subunit of dolichol-phosphate mannose synthase, is tethered to and stabilized on the endoplasmic reticulum membrane by DPM3.
PMID:16293251
CHIP interacts with heat shock factor 1 during heat stress.
PMID:16307917
Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex.
PMID:16809764
Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B (hEST1B) protein from ubiquitin-mediated degradation.
PMID:16831871
CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation.
PMID:17369820
The ubiquitin-selective chaperone CDC-48/p97 links myosin assembly to human myopathy.
PMID:17512523
Parkin interacts with LIM Kinase 1 and reduces its cofilin-phosphorylation activity via ubiquitination.
PMID:18042044
Two different classes of E2 ubiquitin-conjugating enzymes are required for the mono-ubiquitination of proteins and elongation by polyubiquitin chains with a specific topology.
PMID:18292230
Akt and CHIP coregulate tau degradation through coordinated interactions.
PMID:19103148
CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases.
PMID:19423554
Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia.
PMID:19483080
C terminus of Hsc70-interacting protein promotes smooth muscle cell proliferation and survival through ubiquitin-mediated degradation of FoxO1.
PMID:19713937
Ubiquitin ligase ARF-BP1/Mule modulates base excision repair.
PMID:19875381
A proteomic investigation of ligand-dependent HSP90 complexes reveals CHORDC1 as a novel ADP-dependent HSP90-interacting protein.
PMID:19953350
Brain distribution of carboxy terminus of Hsc70-interacting protein (CHIP) and its nuclear translocation in cultured cortical neurons following heat stress or oxygen-glucose deprivation.
PMID:20029029
Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6.
PMID:20588253
CHIP-dependent termination of MEKK2 regulates temporal ERK activation required for proper hyperosmotic response.
PMID:20618441
CHIP participates in protein triage decisions by preferentially ubiquitinating Hsp70-bound substrates.
PMID:20724525
Novel role of C terminus of Hsc70-interacting protein (CHIP) ubiquitin ligase on inhibiting cardiac apoptosis and dysfunction via regulating ERK5-mediated degradation of inducible cAMP early repressor.
PMID:21044950
Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.
PMID:21358815
Ubiquitinylation of α-synuclein by carboxyl terminus Hsp70-interacting protein (CHIP) is regulated by Bcl-2-associated athanogene 5 (BAG5).
PMID:21360678
Label-free quantitative proteomics and SAINT analysis enable interactome mapping for the human Ser/Thr protein phosphatase 5.
PMID:22190034
Global landscape of HIV-human protein complexes.
PMID:22366786
Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy.
PMID:23431407
Distinct roles of molecular chaperones HSP90α and HSP90β in the biogenesis of KCNQ4 channels.
PMID:23973223
The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3.
PMID:23990462
Endoplasmic reticulum protein quality control is determined by cooperative interactions between Hsp/c70 protein and the CHIP E3 ligase.
PMID:24043303
The ubiquitin ligase CHIP prevents SirT6 degradation through noncanonical ubiquitination.
PMID:24510904
Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease.
PMID:24613385
Hsp70 and Hsp90 oppositely regulate TGF-β signaling through CHIP/Stub1.
PMID:24658140
The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells.
PMID:24981860
Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.
PMID:25036637
A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways.
PMID:25260751
The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines.
PMID:25277244
The functional landscape of Hsp27 reveals new cellular processes such as DNA repair and alternative splicing and proposes novel anticancer targets.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:26265139
UBXN2A regulates nicotinic receptor degradation by modulating the E3 ligase activity of CHIP.
PMID:26496610
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
PMID:26634371
Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy.
PMID:26871637
Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
PMID:27353360
The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding.
PMID:27708256
ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation.
PMID:28386764
Roles of tau protein in health and disease.
PMID:29513927
Comparative Protein Interaction Network Analysis Identifies Shared and Distinct Functions for the Human ROCO Proteins.
PMID:29568061
An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.
PMID:29883609
PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylation-Dependent Proteasomal Degradation.
PMID:31046837
Parkinson's disease-associated LRRK2-G2019S mutant acts through regulation of SERCA activity to control ER stress in astrocytes.
PMID:31515488
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
PMID:31980649
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
PMID:32296183
A reference map of the human binary protein interactome.
PMID:32707033
Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:35266954
The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.
PMID:37045861
Interactome dynamics of RAF1-BRAF kinase monomers and dimers.
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
Reactome:R-HSA-1227986
Reactome pathway R-HSA-1227986
Reactome:R-HSA-1918092
Reactome pathway R-HSA-1918092
Reactome:R-HSA-2173788
Reactome pathway R-HSA-2173788
Reactome:R-HSA-2187368
Reactome pathway R-HSA-2187368
Reactome:R-HSA-2187375
Reactome pathway R-HSA-2187375
Reactome:R-HSA-6807134
Reactome pathway R-HSA-6807134
Reactome:R-HSA-9009308
Reactome pathway R-HSA-9009308
Reactome:R-HSA-9009309
Reactome pathway R-HSA-9009309
Reactome:R-HSA-9688831
Reactome pathway R-HSA-9688831
Reactome:R-HSA-9688838
Reactome pathway R-HSA-9688838
Reactome:R-HSA-9796368
Reactome pathway R-HSA-9796368
Reactome:R-HSA-9796387
Reactome pathway R-HSA-9796387

Suggested Questions for Experts

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?

Suggested Experiments

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.

📚 Additional Documentation

Notes

(STUB1-notes.md)

STUB1 (CHIP / E3 ubiquitin-protein ligase CHIP) — research notes

UniProt: Q9UNE7 (CHIP_HUMAN), 303 aa. C-terminus of HSC70-interacting protein.

Core identity

Dual-function protein bridging the chaperone and ubiquitin-proteasome systems:
- N-terminal TPR domain binds HSP70/HSC70 (EEVD) and HSP90 (MEEVD) -> co-chaperone.
- C-terminal U-box domain -> RING-type E3 ubiquitin-protein ligase.
Functions as a homodimer. Ubiquitinates chaperone-bound misfolded/damaged clients
(with E2s e.g. UBE2D, UBE2N/UBE2V1) and targets them for proteasomal degradation
("triage" factor). Also modulates the HSP70/HSP90 chaperone cycle.

  • [file:human/STUB1/STUB1-uniprot.txt "FUNCTION: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation"]
  • [file:human/STUB1/STUB1-uniprot.txt "Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90"]
  • [file:human/STUB1/STUB1-uniprot.txt "The TPR domain is essential for ubiquitination mediated by"]
  • [file:human/STUB1/STUB1-uniprot.txt "SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Mitochondrion."]

Disease

  • SCAR16 [MIM:615768] autosomal-recessive spinocerebellar ataxia (ataxia + hypogonadism),
    caused by loss of CHIP ubiquitin-ligase activity.
  • SCA48 [MIM:618093] autosomal-dominant spinocerebellar ataxia.

Core MFs (per batch-5 guidance)

  1. ubiquitin-protein ligase activity (GO:0061630) + ubiquitin-protein transferase
    activity (GO:0004842) — U-box E3.
  2. Hsp70/Hsp90 co-chaperone binding (GO:0030544 / GO:0051879 / GO:0031072 /
    GO:0051087) via TPR.
  3. Protein quality control for misfolded proteins (GO:0006515).

Review approach (197 annotations, programmatically filled and validated)

  • Core ligase MF/BP (GO:0061630, GO:0004842, GO:0034450, GO:0043161, GO:0006511,
    GO:0000209, GO:0016567, GO:0070534, GO:0006513, GO:0051865, GO:0006515) -> ACCEPT.
  • Chaperone-binding MFs (GO:0030544, GO:0051879, GO:0031072, GO:0051087) -> ACCEPT.
  • Homodimerization (GO:0042803), misfolded protein binding (GO:0051787),
    ubiquitin ligase complex (GO:0000151) -> ACCEPT.
  • Cytoplasm/cytosol (GO:0005737/GO:0005829) -> ACCEPT; nucleus/mitochondrion/ER/Z-disc/
    inclusion body -> KEEP_AS_NON_CORE (documented secondary/specialized localizations).
  • Downstream/regulatory & substrate-specific BP (proteolysis regulation, stress responses,
    cardiac/vascular/immune processes, CMA/mitophagy, TGFbeta/PPAR/ERBB2 signaling) ->
    KEEP_AS_NON_CORE (pleiotropic, substrate-specific consequences of the catalytic MF).
  • 46x protein binding (GO:0005515 IPI): KEEP_AS_NON_CORE (real interactions, uninformative
    term); those with HSP70/HSC70/HSP90 partners MODIFY to Hsp70/Hsp90/heat-shock protein
    binding. HSP-partner PMIDs identified from goa WITH column (P11142=HSPA8, P07900=HSP90AA1,
    P08238=HSP90AB1, P0DMV8/9=HSPA1A/B).

Pn Notes

(STUB1-pn-notes.md)

STUB1 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9UNE7
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07b
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: 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.
  • Existing/core annotation action counts: ACCEPT: 85; KEEP_AS_NON_CORE: 100; MODIFY: 12

PN Consistency Summary

  • Consistency: Strong. Review, notes and PN agree on the dual identity — genuine U-box E3 ligase (GO:0061630 ACCEPT, core) AND HSP70/HSP90 co-chaperone (TPR; GO:0030544/0051879/0031072/0051087 ACCEPT). Review explicitly distinguishes both MFs as the prompt requires. CMA (GO:0061684) and Ub-ligase-complex (GO:0000151) present in review, matching two PN projections. No contradictions.
  • PN story / NEW pressure: PN row 2 asserts CASA/aggrephagy (GO:0035973, verified real, goa_status=new_to_goa). This is NOT in the review (no aggrephagy/CASA/BAG3/HSPB8 annotation anywhere). Review covers mitophagy + CMA as non-core but omits aggrephagy. STUB1 is a bona fide CASA component (BAG3-HSPB8-HSPA8-STUB1) → ADD is defensible (aggrephagy, IBA/IC, non-core). proposed_new_terms is empty.
  • Evidence alignment: PN cites CASA review (tandfonline), CMA review (Nat Rev MCB), PMID:12646216, PMID:40796662 (STUB1/CHIC2). Review is UniProt/GOA-driven (197 IPI/IBA/IEA refs); none of the four PN-specific titles appear in the review. Divergence is in the autophagy-receptor literature.
  • Verdict: Consistent and high-quality; one warranted addition (aggrephagy). Recommended edits: add GO:0035973 aggrephagy as KEEP_AS_NON_CORE supported by CASA literature [YAML]; optionally cite PMID:40796662 / CASA review in references [REF].

Full Consistency Review

  • UniProt: Q9UNE7 (CHIP) · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE (197 annotations reviewed)
  • PN placement: spans 5 rows across CY/ALP/UPS — Cytonuclear|Chaperone|HSP70-HSP90 joint cochaperone|CC-TPR domain and Ub ligase; ALP|...|CASA complex component; ALP|CMA|Effectors|Substrate selection; UPS|E3 ligases|RING variant|UBOX|TPR; UPS|...|STUB1/CHIC2 complex ; PN-node mapping: mapped → GO:0061630 (Ub ligase activity), GO:0031072 (HSP binding), GO:0035973 (aggrephagy, new), GO:0061684 (CMA), GO:0061740 (CMA targeting), GO:0000151 (Ub ligase complex)
  • Consistency: Strong. Review, notes and PN agree on the dual identity — genuine U-box E3 ligase (GO:0061630 ACCEPT, core) AND HSP70/HSP90 co-chaperone (TPR; GO:0030544/0051879/0031072/0051087 ACCEPT). Review explicitly distinguishes both MFs as the prompt requires. CMA (GO:0061684) and Ub-ligase-complex (GO:0000151) present in review, matching two PN projections. No contradictions.
  • PN story / NEW pressure: PN row 2 asserts CASA/aggrephagy (GO:0035973, verified real, goa_status=new_to_goa). This is NOT in the review (no aggrephagy/CASA/BAG3/HSPB8 annotation anywhere). Review covers mitophagy + CMA as non-core but omits aggrephagy. STUB1 is a bona fide CASA component (BAG3-HSPB8-HSPA8-STUB1) → ADD is defensible (aggrephagy, IBA/IC, non-core). proposed_new_terms is empty.
  • Mapping strategy: Node mappings are sound and conservative (E3-complex node → GO:0000151 membership not catalytic activity; CMA class held context_only). No change needed; aggrephagy is the only genuinely novel projection.
  • Evidence alignment: PN cites CASA review (tandfonline), CMA review (Nat Rev MCB), PMID:12646216, PMID:40796662 (STUB1/CHIC2). Review is UniProt/GOA-driven (197 IPI/IBA/IEA refs); none of the four PN-specific titles appear in the review. Divergence is in the autophagy-receptor literature.
  • Verdict: Consistent and high-quality; one warranted addition (aggrephagy). Recommended edits: add GO:0035973 aggrephagy as KEEP_AS_NON_CORE supported by CASA literature [YAML]; optionally cite PMID:40796662 / CASA review in references [REF].

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/STUB1/STUB1-ai-review.yaml
  • PN workbook rows: 5

PN row 1: Cytonuclear proteostasis | Chaperone | HSP70-HSP90 system integration | HSP70-HSP90 joint cochaperone | CC-TPR domain and Ub ligase

  • UniProt: Q9UNE7
  • In branches: CY, ALP, UPS
  • PN-node mapping records (path + ancestors):
    • [subtype] Cytonuclear proteostasis|Chaperone|HSP70-HSP90 system integration|HSP70-HSP90 joint cochaperone|CC-TPR domain and Ub ligase
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0061630 ubiquitin protein ligase activity]
      rationale: This PN subtype explicitly denotes TPR-containing ubiquitin ligases in the HSP70/HSP90 co-chaperone branch. The shared catalytic assertion is ubiquitin protein ligase activity.
    • [type] Cytonuclear proteostasis|Chaperone|HSP70-HSP90 system integration|HSP70-HSP90 joint cochaperone
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0031072 heat shock protein binding]
      rationale: This PN type groups joint HSP70/HSP90 cochaperones. The shared mechanistic assertion is binding heat-shock-protein chaperones, while narrower domain labels remain non-mapping unless they carry an independent activity.
    • [group] Cytonuclear proteostasis|Chaperone|HSP70-HSP90 system integration
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN category rather than a specific GO class. The member genes span multiple activities, complexes, or contexts, so propagation from this node would overstate the shared biology; use narrower child or gene-level curations.
    • [class] Cytonuclear proteostasis|Chaperone
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN category rather than a specific GO class. The member genes span multiple activities, complexes, or contexts, so propagation from this node would overstate the shared biology; use narrower child or gene-level curations.
    • [branch] Cytonuclear proteostasis
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

PN row 2: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Chaperone assisted selective autophagy | CASA complex component

  • UniProt: Q9UNE7
  • In branches: CY, ALP, UPS
  • Notes: HSP90 cochaperone. Participates in chaperone-assisted selective autophagy by forming the CASA complex (HSPA8, BAG3, HSPB8, and STUB1) that delivers ubiquitinated substrates to the to the autophagosome
  • PN references (titles):
    • Full article: The chaperone-assisted selective autophagy complex dynamics and dysfunctions (tandfonline.com)
  • PN-node mapping records (path + ancestors):
    • [subtype] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Chaperone assisted selective autophagy|CASA complex component
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0035973 aggrephagy]
      rationale: The PN CASA subtype covers BAG3-HSPB8-HSP70-system machinery that directs damaged or aggregation-prone substrates into selective autophagic clearance. GO lacks a dedicated CASA term in the current cache, and this subtype includes chaperones and cofactors beyond pure cargo adaptors, so aggrephagy is the closest available process target.
    • [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Chaperone assisted selective autophagy
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a contextual PN role. The label is useful for curator triage, but by itself does not support a universal GO assertion for all member genes beyond curated ancestor or child mappings.
    • [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
    • [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 3: Autophagy-Lysosome Pathway | Chaperone-mediated autophagy | Effectors of chaperone-mediated autophagy | Substrate selection

  • UniProt: Q9UNE7
  • In branches: CY, ALP, UPS
  • Notes: An HSP90 cochaperone. Works with HSPA8 in autophagy substrate selection.
  • PN references (titles):
    • The coming of age of chaperone-mediated autophagy | Nature Reviews Molecular Cell Biology
  • PN-node mapping records (path + ancestors):
    • [type] Autophagy-Lysosome Pathway|Chaperone-mediated autophagy|Effectors of chaperone-mediated autophagy|Substrate selection
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy]
      rationale: This leaf denotes substrate-selection machinery for CMA. The GO protein-targeting term preserves the mechanistic role without relying on broad class-level CMA propagation.
    • [group] Autophagy-Lysosome Pathway|Chaperone-mediated autophagy|Effectors of chaperone-mediated autophagy
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0061684 chaperone-mediated autophagy]
      rationale: This group covers direct CMA machinery and substrate-selection effectors, unlike the broader CMA class that also includes regulators. Propagation to chaperone-mediated autophagy is appropriate at this narrower level.
    • [class] Autophagy-Lysosome Pathway|Chaperone-mediated autophagy
      status=context_only scope=too_broad_to_propagate GO=[GO:0061684 chaperone-mediated autophagy]
      rationale: The class label matches the GO CMA process, but the subtree includes both effectors and positive or negative modulators. The relation is retained as context so modulators are not projected as direct CMA participants unless a narrower node supports it.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 4: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | RING variant | UBOX | TPR

  • UniProt: Q9UNE7
  • In branches: CY, ALP, UPS
  • Signature domains: IPR003613
  • Auxiliary domains: IPR019734
  • PN references (titles):
    • 12646216 / rev
  • PN-node mapping records (path + ancestors):
    • [subtype] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|RING variant|UBOX|TPR
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a narrower E3-ligase architecture, component, or domain subdivision already covered by the curated parent E3 mapping. No additional direct GO mapping is needed at this node.
    • [type] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|RING variant|UBOX
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a narrower E3-ligase architecture, component, or domain subdivision already covered by the curated parent E3 mapping. No additional direct GO mapping is needed at this node.
    • [group] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|RING variant
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0061630 ubiquitin protein ligase activity]
      rationale: This PN group is a catalytic ubiquitin E3 ligase bucket. The shared GO molecular-function target is ubiquitin protein ligase activity.
    • [class] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases
      status=context_only scope=too_broad_to_propagate GO=[GO:0061630 ubiquitin protein ligase activity]
      rationale: This class is a genuine E3-ligase context, but its descendants include catalytic ligases, cullin scaffolds, substrate receptors, adaptors, cofactors, regulators, and UBL modifier systems. A class-level propagation would over-annotate.
    • [branch] Ubiquitin Proteasome System
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.

PN row 5: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | idiosyncratic UBOX complex | STUB1/CHIC2 complex | catalytic / UBOX / TPR

  • UniProt: Q9UNE7
  • In branches: CY, ALP, UPS
  • Signature domains: (none)
  • Auxiliary domains: IPR003613, IPR019734
  • PN references (titles):
    • 40796662
  • PN-node mapping records (path + ancestors):
    • [subtype] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|idiosyncratic UBOX complex|STUB1/CHIC2 complex|catalytic / UBOX / TPR
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a narrower E3-ligase architecture, component, or domain subdivision already covered by the curated parent E3 mapping. No additional direct GO mapping is needed at this node.
    • [type] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|idiosyncratic UBOX complex|STUB1/CHIC2 complex
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a narrower E3-ligase architecture, component, or domain subdivision already covered by the curated parent E3 mapping. No additional direct GO mapping is needed at this node.
    • [group] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|idiosyncratic UBOX complex
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0000151 ubiquitin ligase complex]
      rationale: This PN group is an E3 ligase complex bucket. The safest shared GO target is ubiquitin ligase complex membership rather than assigning catalytic activity to every subunit.
    • [class] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases
      status=context_only scope=too_broad_to_propagate GO=[GO:0061630 ubiquitin protein ligase activity]
      rationale: This class is a genuine E3-ligase context, but its descendants include catalytic ligases, cullin scaffolds, substrate receptors, adaptors, cofactors, regulators, and UBL modifier systems. A class-level propagation would over-annotate.
    • [branch] Ubiquitin Proteasome System
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.

Projected GO annotations (7)

  • GO:0031072 heat shock protein binding | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Cytonuclear proteostasis|Chaperone|HSP70-HSP90 system integration|HSP70-HSP90 joint cochaperone
  • GO:0061630 ubiquitin protein ligase activity | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Cytonuclear proteostasis|Chaperone|HSP70-HSP90 system integration|HSP70-HSP90 joint cochaperone|CC-TPR domain and Ub ligase
  • GO:0035973 aggrephagy | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Chaperone assisted selective autophagy|CASA complex component
  • GO:0061684 chaperone-mediated autophagy | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Chaperone-mediated autophagy|Effectors of chaperone-mediated autophagy
  • GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Chaperone-mediated autophagy|Effectors of chaperone-mediated autophagy|Substrate selection
  • GO:0061630 ubiquitin protein ligase activity | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|RING variant
  • GO:0000151 ubiquitin ligase complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|idiosyncratic UBOX complex

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: Q9UNE7
gene_symbol: STUB1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: '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.'
alternative_products:
- name: '1'
  id: Q9UNE7-1
- name: '2'
  id: Q9UNE7-2
  sequence_note: VSP_015947
existing_annotations:
- term:
    id: GO:0045862
    label: positive regulation of proteolysis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: positive regulation of proteolysis is a downstream process of CHIP's ubiquitin-ligase / quality-control activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: protein polyubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0006515
    label: protein quality control for misfolded or incompletely synthesized proteins
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: CHIP performs protein quality control by ubiquitinating misfolded chaperone clients for degradation.
    action: ACCEPT
    reason: 'Central CHIP function: triage of misfolded chaperone substrates to the proteasome.'
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0030018
    label: Z disc
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'Z disc: specialized localization (Z-disc / nuclear inclusion body) in particular contexts.'
    action: KEEP_AS_NON_CORE
    reason: Context-specific localization; peripheral to CHIP's principal cytoplasmic QC role.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0071218
    label: cellular response to misfolded protein
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'cellular response to misfolded protein: CHIP participates in cellular stress/misfolded-protein responses via its triage activity.'
    action: KEEP_AS_NON_CORE
    reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: CHIP translocates to the nucleus under some conditions; nuclear pool is documented but secondary.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists Nucleus (translocates to the nucleus); non-core relative to the cytoplasmic function.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: Translocates to the nucleus
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: CHIP localizes to mitochondria, linked to mitochondrial QC/mitophagy.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists Mitochondrion (by similarity); a specialized non-core localization.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: Mitochondrion
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'signal transduction: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: protein ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0030163
    label: protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: protein catabolic process is a downstream process of CHIP's ubiquitin-ligase / quality-control activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0033554
    label: cellular response to stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'cellular response to stress: CHIP participates in cellular stress/misfolded-protein responses via its triage activity.'
    action: KEEP_AS_NON_CORE
    reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16275660
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as heat shock protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0031072
      label: heat shock protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16293251
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as heat shock protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0031072
      label: heat shock protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16307917
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp90 protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0051879
      label: Hsp90 protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19875381
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp90 protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0051879
      label: Hsp90 protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20029029
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20588253
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20618441
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as heat shock protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0031072
      label: heat shock protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21044950
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21358815
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21360678
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp90 protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0051879
      label: Hsp90 protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22190034
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23973223
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24510904
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24658140
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24981860
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25036637
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp90 protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0051879
      label: Hsp90 protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25260751
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25277244
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26871637
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29513927
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29568061
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp70 protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0030544
      label: Hsp70 protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31046837
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31980649
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32707033
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp70 protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0030544
      label: Hsp70 protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35266954
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37045861
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'MAPK cascade: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0002931
    label: response to ischemia
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'response to ischemia: CHIP participates in cellular stress/misfolded-protein responses via its triage activity.'
    action: KEEP_AS_NON_CORE
    reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0006515
    label: protein quality control for misfolded or incompletely synthesized proteins
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: CHIP performs protein quality control by ubiquitinating misfolded chaperone clients for degradation.
    action: ACCEPT
    reason: 'Central CHIP function: triage of misfolded chaperone substrates to the proteasome.'
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0010614
    label: negative regulation of cardiac muscle hypertrophy
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'negative regulation of cardiac muscle hypertrophy: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0030018
    label: Z disc
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: 'Z disc: specialized localization (Z-disc / nuclear inclusion body) in particular contexts.'
    action: KEEP_AS_NON_CORE
    reason: Context-specific localization; peripheral to CHIP's principal cytoplasmic QC role.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0030968
    label: endoplasmic reticulum unfolded protein response
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'endoplasmic reticulum unfolded protein response: CHIP participates in cellular stress/misfolded-protein responses via its triage activity.'
    action: KEEP_AS_NON_CORE
    reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0031398
    label: positive regulation of protein ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: positive regulation of protein ubiquitination is a downstream process of CHIP's ubiquitin-ligase / quality-control activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: 'ubiquitin protein ligase binding: a specific partner/substrate-binding annotation for CHIP.'
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0034392
    label: negative regulation of smooth muscle cell apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'negative regulation of smooth muscle cell apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0034393
    label: positive regulation of smooth muscle cell apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'positive regulation of smooth muscle cell apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0034450
    label: ubiquitin-ubiquitin ligase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: CHIP elongates ubiquitin chains on substrates (ubiquitin-ubiquitin ligase / E4-like activity), consistent with its polyubiquitination role.
    action: ACCEPT
    reason: Supported by CHIP's documented polyubiquitination of chaperone clients and chain elongation activity.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'cellular response to heat: CHIP participates in cellular stress/misfolded-protein responses via its triage activity.'
    action: KEEP_AS_NON_CORE
    reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0035359
    label: negative regulation of peroxisome proliferator activated receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'negative regulation of peroxisome proliferator activated receptor signaling pathway: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: CHIP forms a homodimer, required for its E3 ligase activity.
    action: ACCEPT
    reason: CHIP functions as a homodimer; homodimerization is a genuine, specific molecular feature.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'negative regulation of apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0051087
    label: protein-folding chaperone binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: CHIP binds the folding chaperones HSP70/HSC70/HSP90, consistent with its co-chaperone role.
    action: ACCEPT
    reason: Supported by UniProt FUNCTION; chaperone binding underpins CHIP's substrate-triage activity.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0061684
    label: chaperone-mediated autophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'chaperone-mediated autophagy: CHIP modulates chaperone-mediated autophagy/mitophagy and chaperone complex assembly.'
    action: KEEP_AS_NON_CORE
    reason: Documented co-chaperone-linked process; non-core relative to CHIP's E3-ligase and chaperone-binding MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0071218
    label: cellular response to misfolded protein
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'cellular response to misfolded protein: CHIP participates in cellular stress/misfolded-protein responses via its triage activity.'
    action: KEEP_AS_NON_CORE
    reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0071456
    label: cellular response to hypoxia
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'cellular response to hypoxia: CHIP participates in cellular stress/misfolded-protein responses via its triage activity.'
    action: KEEP_AS_NON_CORE
    reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:1901526
    label: positive regulation of mitophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'positive regulation of mitophagy: CHIP modulates chaperone-mediated autophagy/mitophagy and chaperone complex assembly.'
    action: KEEP_AS_NON_CORE
    reason: Documented co-chaperone-linked process; non-core relative to CHIP's E3-ligase and chaperone-binding MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:1904694
    label: negative regulation of vascular associated smooth muscle contraction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'negative regulation of vascular associated smooth muscle contraction: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0030512
    label: negative regulation of transforming growth factor beta receptor signaling pathway
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2173788
  qualifier: involved_in
  review:
    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.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0038128
    label: ERBB2 signaling pathway
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1227986
  qualifier: involved_in
  review:
    summary: 'ERBB2 signaling pathway: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6807134
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9009308
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: CHIP translocates to the nucleus under some conditions; nuclear pool is documented but secondary.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists Nucleus (translocates to the nucleus); non-core relative to the cytoplasmic function.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: Translocates to the nucleus
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:17369820
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:23973223
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: CHIP localizes to mitochondria, linked to mitochondrial QC/mitophagy.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists Mitochondrion (by similarity); a specialized non-core localization.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: Mitochondrion
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: EXP
  original_reference_id: PMID:11557750
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: EXP
  original_reference_id: PMID:15466472
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0002931
    label: response to ischemia
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'response to ischemia: CHIP participates in cellular stress/misfolded-protein responses via its triage activity.'
    action: KEEP_AS_NON_CORE
    reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: CHIP translocates to the nucleus under some conditions; nuclear pool is documented but secondary.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists Nucleus (translocates to the nucleus); non-core relative to the cytoplasmic function.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: Translocates to the nucleus
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'cellular response to heat: CHIP participates in cellular stress/misfolded-protein responses via its triage activity.'
    action: KEEP_AS_NON_CORE
    reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0071456
    label: cellular response to hypoxia
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'cellular response to hypoxia: CHIP participates in cellular stress/misfolded-protein responses via its triage activity.'
    action: KEEP_AS_NON_CORE
    reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0035359
    label: negative regulation of peroxisome proliferator activated receptor signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'negative regulation of peroxisome proliferator activated receptor signaling pathway: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:19713937
  qualifier: involved_in
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1918092
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2187368
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:23990462
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0036503
    label: ERAD pathway
  evidence_type: IMP
  original_reference_id: PMID:23990462
  qualifier: involved_in
  review:
    summary: ERAD pathway is a downstream process of CHIP's ubiquitin-ligase / quality-control activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0034393
    label: positive regulation of smooth muscle cell apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'positive regulation of smooth muscle cell apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'MAPK cascade: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19483080
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20724525
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0034392
    label: negative regulation of smooth muscle cell apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'negative regulation of smooth muscle cell apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0034392
    label: negative regulation of smooth muscle cell apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:20724525
  qualifier: involved_in
  review:
    summary: 'negative regulation of smooth muscle cell apoptotic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:1901526
    label: positive regulation of mitophagy
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'positive regulation of mitophagy: CHIP modulates chaperone-mediated autophagy/mitophagy and chaperone complex assembly.'
    action: KEEP_AS_NON_CORE
    reason: Documented co-chaperone-linked process; non-core relative to CHIP's E3-ligase and chaperone-binding MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0045862
    label: positive regulation of proteolysis
  evidence_type: IMP
  original_reference_id: PMID:26634371
  qualifier: involved_in
  review:
    summary: positive regulation of proteolysis is a downstream process of CHIP's ubiquitin-ligase / quality-control activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26265139
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IDA
  original_reference_id: PMID:26265139
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:1904294
    label: positive regulation of ERAD pathway
  evidence_type: IMP
  original_reference_id: PMID:26265139
  qualifier: involved_in
  review:
    summary: positive regulation of ERAD pathway is a downstream process of CHIP's ubiquitin-ligase / quality-control activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0030512
    label: negative regulation of transforming growth factor beta receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:15781469
  qualifier: involved_in
  review:
    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.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:15781469
  qualifier: involved_in
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IMP
  original_reference_id: PMID:15781469
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0070412
    label: R-SMAD binding
  evidence_type: IPI
  original_reference_id: PMID:15781469
  qualifier: enables
  review:
    summary: 'R-SMAD binding: a specific partner/substrate-binding annotation for CHIP.'
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IPI
  original_reference_id: PMID:23990462
  qualifier: enables
  review:
    summary: CHIP forms a homodimer, required for its E3 ligase activity.
    action: ACCEPT
    reason: CHIP functions as a homodimer; homodimerization is a genuine, specific molecular feature.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: CHIP forms a homodimer, required for its E3 ligase activity.
    action: ACCEPT
    reason: CHIP functions as a homodimer; homodimerization is a genuine, specific molecular feature.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IDA
  original_reference_id: PMID:24043303
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:23973223
  qualifier: is_active_in
  review:
    summary: CHIP translocates to the nucleus under some conditions; nuclear pool is documented but secondary.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists Nucleus (translocates to the nucleus); non-core relative to the cytoplasmic function.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: Translocates to the nucleus
- term:
    id: GO:0006513
    label: protein monoubiquitination
  evidence_type: IDA
  original_reference_id: PMID:24043303
  qualifier: involved_in
  review:
    summary: protein monoubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IDA
  original_reference_id: PMID:24043303
  qualifier: involved_in
  review:
    summary: protein stabilization is a downstream process of CHIP's ubiquitin-ligase / quality-control activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0048156
    label: tau protein binding
  evidence_type: NAS
  original_reference_id: PMID:28386764
  qualifier: enables
  review:
    summary: CHIP binds tau (MAPT), a chaperone client it ubiquitinates.
    action: KEEP_AS_NON_CORE
    reason: Real substrate interaction (tau); informative but a specific client-binding annotation, non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29883609
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IMP
  original_reference_id: PMID:29883609
  qualifier: involved_in
  review:
    summary: protein ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:29883609
  qualifier: involved_in
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IMP
  original_reference_id: PMID:23990462
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:14610072
  qualifier: involved_in
  review:
    summary: protein ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IDA
  original_reference_id: PMID:14610072
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16207813
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp70 protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0030544
      label: Hsp70 protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0031072
    label: heat shock protein binding
  evidence_type: IPI
  original_reference_id: PMID:16207813
  qualifier: enables
  review:
    summary: CHIP binds heat shock proteins (HSP70/HSC70/HSP90) through its TPR domain.
    action: ACCEPT
    reason: Supported by UniProt FUNCTION; binding HSP70/HSP90 chaperones is central to CHIP's triage role.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0051087
    label: protein-folding chaperone binding
  evidence_type: IPI
  original_reference_id: PMID:16207813
  qualifier: enables
  review:
    summary: CHIP binds the folding chaperones HSP70/HSC70/HSP90, consistent with its co-chaperone role.
    action: ACCEPT
    reason: Supported by UniProt FUNCTION; chaperone binding underpins CHIP's substrate-triage activity.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IGI
  original_reference_id: PMID:16207813
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0101031
    label: protein folding chaperone complex
  evidence_type: IPI
  original_reference_id: PMID:16207813
  qualifier: part_of
  review:
    summary: CHIP associates with HSP70/HSP90 chaperone complexes as a co-chaperone.
    action: KEEP_AS_NON_CORE
    reason: CHIP partners with the folding-chaperone machinery; a reasonable complex annotation, non-core relative to its ligase/co-chaperone MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: ISS
  original_reference_id: PMID:18292230
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: IGI
  original_reference_id: PMID:18292230
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: TAS
  original_reference_id: PMID:19953350
  qualifier: involved_in
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27708256
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as heat shock protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0031072
      label: heat shock protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24613385
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0030512
    label: negative regulation of transforming growth factor beta receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:24613385
  qualifier: involved_in
  review:
    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.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0030544
    label: Hsp70 protein binding
  evidence_type: IPI
  original_reference_id: PMID:24613385
  qualifier: enables
  review:
    summary: CHIP binds HSP70/HSC70 via its TPR domain; Hsp70 protein binding is a core co-chaperone molecular function.
    action: ACCEPT
    reason: Supported by UniProt FUNCTION (modulates Hsp70/Hsc70/Hsp90) and the TPR-domain HSP70-binding role of CHIP.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:24613385
  qualifier: involved_in
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0046332
    label: SMAD binding
  evidence_type: IPI
  original_reference_id: PMID:24613385
  qualifier: enables
  review:
    summary: 'SMAD binding: a specific partner/substrate-binding annotation for CHIP.'
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IDA
  original_reference_id: PMID:24613385
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23431407
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27353360
  qualifier: enables
  review:
    summary: Interaction with an HSP70/HSP90-family chaperone partner. Bare protein binding is uninformative; better captured as Hsp90 protein binding.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0051879
      label: Hsp90 protein binding
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16809764
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:16809764
  qualifier: involved_in
  review:
    summary: protein ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IMP
  original_reference_id: PMID:16809764
  qualifier: involved_in
  review:
    summary: protein ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: IDA
  original_reference_id: PMID:16809764
  qualifier: involved_in
  review:
    summary: regulation of protein stability is a downstream process of CHIP's ubiquitin-ligase / quality-control activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IDA
  original_reference_id: PMID:16809764
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IMP
  original_reference_id: PMID:16809764
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0030544
    label: Hsp70 protein binding
  evidence_type: IDA
  original_reference_id: PMID:23990462
  qualifier: enables
  review:
    summary: CHIP binds HSP70/HSC70 via its TPR domain; Hsp70 protein binding is a core co-chaperone molecular function.
    action: ACCEPT
    reason: Supported by UniProt FUNCTION (modulates Hsp70/Hsc70/Hsp90) and the TPR-domain HSP70-binding role of CHIP.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IDA
  original_reference_id: PMID:16275660
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IDA
  original_reference_id: PMID:19103148
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin protein ligase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0000151
    label: ubiquitin ligase complex
  evidence_type: IDA
  original_reference_id: PMID:12150907
  qualifier: part_of
  review:
    summary: CHIP functions within ubiquitin ligase complexes (with E2 enzymes and chaperones).
    action: ACCEPT
    reason: Consistent with CHIP's E3 ligase activity acting in complex with E2s and chaperone-bound substrates.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0001664
    label: G protein-coupled receptor binding
  evidence_type: IPI
  original_reference_id: PMID:12150907
  qualifier: enables
  review:
    summary: 'G protein-coupled receptor binding: a specific partner/substrate-binding annotation for CHIP.'
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:12150907
  qualifier: located_in
  review:
    summary: CHIP participates in ER-associated degradation (ERAD) of certain substrates.
    action: KEEP_AS_NON_CORE
    reason: ER context reflects CHIP's ERAD role (e.g. CHRNA3, CYP3A4); non-core localization.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:12150907
  qualifier: enables
  review:
    summary: 'ubiquitin protein ligase binding: a specific partner/substrate-binding annotation for CHIP.'
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0000151
    label: ubiquitin ligase complex
  evidence_type: IDA
  original_reference_id: PMID:16275660
  qualifier: part_of
  review:
    summary: CHIP functions within ubiquitin ligase complexes (with E2 enzymes and chaperones).
    action: ACCEPT
    reason: Consistent with CHIP's E3 ligase activity acting in complex with E2s and chaperone-bound substrates.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IDA
  original_reference_id: PMID:16275660
  qualifier: involved_in
  review:
    summary: protein polyubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1918092
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2187368
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2187375
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6807134
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9009308
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9009309
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9688831
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9688838
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9796368
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9796387
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22366786
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0000151
    label: ubiquitin ligase complex
  evidence_type: IDA
  original_reference_id: PMID:16307917
  qualifier: part_of
  review:
    summary: CHIP functions within ubiquitin ligase complexes (with E2 enzymes and chaperones).
    action: ACCEPT
    reason: Consistent with CHIP's E3 ligase activity acting in complex with E2s and chaperone-bound substrates.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0051865
    label: protein autoubiquitination
  evidence_type: IDA
  original_reference_id: PMID:16307917
  qualifier: involved_in
  review:
    summary: protein autoubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0070534
    label: protein K63-linked ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:16307917
  qualifier: involved_in
  review:
    summary: protein K63-linked ubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IMP
  original_reference_id: PMID:19713937
  qualifier: involved_in
  review:
    summary: protein polyubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IMP
  original_reference_id: PMID:19713937
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:19713937
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19423554
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IDA
  original_reference_id: PMID:15466472
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0051865
    label: protein autoubiquitination
  evidence_type: IDA
  original_reference_id: PMID:18042044
  qualifier: involved_in
  review:
    summary: protein autoubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: IPI
  original_reference_id: PMID:17512523
  qualifier: enables
  review:
    summary: 'kinase binding: a specific partner/substrate-binding annotation for CHIP.'
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:16831871
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0006515
    label: protein quality control for misfolded or incompletely synthesized proteins
  evidence_type: IDA
  original_reference_id: PMID:16831871
  qualifier: involved_in
  review:
    summary: CHIP performs protein quality control by ubiquitinating misfolded chaperone clients for degradation.
    action: ACCEPT
    reason: 'Central CHIP function: triage of misfolded chaperone substrates to the proteasome.'
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0031398
    label: positive regulation of protein ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:16831871
  qualifier: involved_in
  review:
    summary: positive regulation of protein ubiquitination is a downstream process of CHIP's ubiquitin-ligase / quality-control activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0042405
    label: nuclear inclusion body
  evidence_type: IDA
  original_reference_id: PMID:16831871
  qualifier: located_in
  review:
    summary: 'nuclear inclusion body: specialized localization (Z-disc / nuclear inclusion body) in particular contexts.'
    action: KEEP_AS_NON_CORE
    reason: Context-specific localization; peripheral to CHIP's principal cytoplasmic QC role.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0051787
    label: misfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:16831871
  qualifier: enables
  review:
    summary: CHIP recognizes misfolded chaperone-bound clients for ubiquitination.
    action: ACCEPT
    reason: Supported by UniProt FUNCTION (targets misfolded chaperone substrates); misfolded protein binding underlies substrate selection.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0071218
    label: cellular response to misfolded protein
  evidence_type: IDA
  original_reference_id: PMID:16831871
  qualifier: involved_in
  review:
    summary: 'cellular response to misfolded protein: CHIP participates in cellular stress/misfolded-protein responses via its triage activity.'
    action: KEEP_AS_NON_CORE
    reason: Stress/misfolded-protein response context downstream of CHIP's quality-control role; non-core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0090035
    label: positive regulation of chaperone-mediated protein complex assembly
  evidence_type: IDA
  original_reference_id: PMID:16831871
  qualifier: involved_in
  review:
    summary: 'positive regulation of chaperone-mediated protein complex assembly: CHIP modulates chaperone-mediated autophagy/mitophagy and chaperone complex assembly.'
    action: KEEP_AS_NON_CORE
    reason: Documented co-chaperone-linked process; non-core relative to CHIP's E3-ligase and chaperone-binding MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0051879
    label: Hsp90 protein binding
  evidence_type: IDA
  original_reference_id: PMID:11146632
  qualifier: enables
  review:
    summary: CHIP binds HSP90 via its TPR domain; Hsp90 protein binding is a core co-chaperone molecular function.
    action: ACCEPT
    reason: Supported by UniProt FUNCTION (modulates Hsp70/Hsc70/Hsp90); CHIP is a TPR co-chaperone of HSP90.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0034450
    label: ubiquitin-ubiquitin ligase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: CHIP elongates ubiquitin chains on substrates (ubiquitin-ubiquitin ligase / E4-like activity), consistent with its polyubiquitination role.
    action: ACCEPT
    reason: Supported by CHIP's documented polyubiquitination of chaperone clients and chain elongation activity.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:16280320
  qualifier: enables
  review:
    summary: 'enzyme binding: a specific partner/substrate-binding annotation for CHIP.'
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11146632
  qualifier: enables
  review:
    summary: Protein interaction captured by an interactome/IPI study (substrate or partner). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (often a CHIP substrate or partner) but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:10330192
  qualifier: located_in
  review:
    summary: CHIP is predominantly cytoplasmic/cytosolic, where it triages chaperone clients.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm/cytosol is the principal compartment.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0030544
    label: Hsp70 protein binding
  evidence_type: IDA
  original_reference_id: PMID:10330192
  qualifier: enables
  review:
    summary: CHIP binds HSP70/HSC70 via its TPR domain; Hsp70 protein binding is a core co-chaperone molecular function.
    action: ACCEPT
    reason: Supported by UniProt FUNCTION (modulates Hsp70/Hsc70/Hsp90) and the TPR-domain HSP70-binding role of CHIP.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- term:
    id: GO:0030911
    label: TPR domain binding
  evidence_type: IDA
  original_reference_id: PMID:11146632
  qualifier: enables
  review:
    summary: CHIP's TPR domain mediates chaperone binding; this annotation reflects TPR-mediated interactions.
    action: KEEP_AS_NON_CORE
    reason: Real TPR-mediated interaction property; captured more informatively by the Hsp70/Hsp90 binding terms.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: The TPR domain is essential for ubiquitination mediated by
- term:
    id: GO:0031398
    label: positive regulation of protein ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:11146632
  qualifier: involved_in
  review:
    summary: positive regulation of protein ubiquitination is a downstream process of CHIP's ubiquitin-ligase / quality-control activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0031943
    label: regulation of glucocorticoid metabolic process
  evidence_type: IDA
  original_reference_id: PMID:11146632
  qualifier: involved_in
  review:
    summary: 'regulation of glucocorticoid metabolic process: a substrate-specific/pleiotropic process attributed to CHIP via degradation of a particular client.'
    action: KEEP_AS_NON_CORE
    reason: Downstream, substrate-specific physiological consequence of CHIP-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0032436
    label: positive regulation of proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:11146632
  qualifier: involved_in
  review:
    summary: positive regulation of proteasomal ubiquitin-dependent protein catabolic process is a downstream process of CHIP's ubiquitin-ligase / quality-control activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation downstream of CHIP's E3-ligase-mediated degradation; non-core relative to the catalytic MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: TAS
  original_reference_id: PMID:16307917
  qualifier: enables
  review:
    summary: 'protein-macromolecule adaptor activity: a specific partner/substrate-binding annotation for CHIP.'
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction property of CHIP; non-core relative to its E3-ligase and chaperone-binding core MFs.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IDA
  original_reference_id: PMID:15781469
  qualifier: involved_in
  review:
    summary: protein polyubiquitination is a direct outcome of CHIP's E3 ubiquitin-ligase activity on its substrates.
    action: ACCEPT
    reason: Directly tied to CHIP's polyubiquitination/ubiquitination activity (U-box E3 ligase).
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: TAS
  original_reference_id: PMID:16307917
  qualifier: enables
  review:
    summary: STUB1/CHIP is a U-box-type E3 ubiquitin-protein ligase; ubiquitin-protein transferase activity is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- term:
    id: GO:0031371
    label: ubiquitin conjugating enzyme complex
  evidence_type: TAS
  original_reference_id: PMID:16307917
  qualifier: part_of
  review:
    summary: CHIP acts together with E2 ubiquitin-conjugating enzymes (e.g. UBE2N/UBE2D).
    action: KEEP_AS_NON_CORE
    reason: Reflects CHIP-E2 cooperation; non-core relative to its E3 ligase MF.
    supported_by:
    - reference_id: file:human/STUB1/STUB1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs using sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs by Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic GO annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10330192
  title: 'Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions.'
  findings: []
- id: PMID:11146632
  title: 'The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins.'
  findings: []
- id: PMID:11557750
  title: 'CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation.'
  findings: []
- id: PMID:12150907
  title: CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity.
  findings: []
- id: PMID:14610072
  title: 'Dimerization of the human E3 ligase CHIP via a coiled-coil domain is essential for its activity.'
  findings: []
- id: PMID:15466472
  title: 'Ubiquitylation of neuronal nitric-oxide synthase by CHIP, a chaperone-dependent E3 ligase.'
  findings: []
- id: PMID:15781469
  title: CHIP controls the sensitivity of transforming growth factor-beta signaling by modulating the basal level of Smad3 through ubiquitin-mediated degradation.
  findings: []
- id: PMID:16207813
  title: BAG-2 acts as an inhibitor of the chaperone-associated ubiquitin ligase CHIP.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: GOA-anchored (this PMID supports GO:0061630 ubiquitin protein ligase activity, GO:0051087 protein-folding chaperone binding, and GO:0101031 protein folding chaperone complex in STUB1-goa.tsv); supports CHIP/STUB1 as the chaperone-associated ubiquitin ligase, anchoring its E3 ligase and co-chaperone core functions.
- id: PMID:16275660
  title: Identification of VCP/p97, carboxyl terminus of Hsp70-interacting protein (CHIP), and amphiphysin II interaction partners using membrane-based human proteome arrays.
  findings: []
- id: PMID:16280320
  title: 'DPM1, the catalytic subunit of dolichol-phosphate mannose synthase, is tethered to and stabilized on the endoplasmic reticulum membrane by DPM3.'
  findings: []
- id: PMID:16293251
  title: CHIP interacts with heat shock factor 1 during heat stress.
  findings: []
- id: PMID:16307917
  title: 'Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex.'
  findings: []
- id: PMID:16809764
  title: Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B (hEST1B) protein from ubiquitin-mediated degradation.
  findings: []
- id: PMID:16831871
  title: 'CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation.'
  findings: []
- id: PMID:17369820
  title: 'The ubiquitin-selective chaperone CDC-48/p97 links myosin assembly to human myopathy.'
  findings: []
- id: PMID:17512523
  title: 'Parkin interacts with LIM Kinase 1 and reduces its cofilin-phosphorylation activity via ubiquitination.'
  findings: []
- id: PMID:18042044
  title: 'Two different classes of E2 ubiquitin-conjugating enzymes are required for the mono-ubiquitination of proteins and elongation by polyubiquitin chains with a specific topology.'
  findings: []
- id: PMID:18292230
  title: Akt and CHIP coregulate tau degradation through coordinated interactions.
  findings: []
- id: PMID:19103148
  title: CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases.
  findings: []
- id: PMID:19423554
  title: 'Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia.'
  findings: []
- id: PMID:19483080
  title: C terminus of Hsc70-interacting protein promotes smooth muscle cell proliferation and survival through ubiquitin-mediated degradation of FoxO1.
  findings: []
- id: PMID:19713937
  title: 'Ubiquitin ligase ARF-BP1/Mule modulates base excision repair.'
  findings: []
- id: PMID:19875381
  title: A proteomic investigation of ligand-dependent HSP90 complexes reveals CHORDC1 as a novel ADP-dependent HSP90-interacting protein.
  findings: []
- id: PMID:19953350
  title: 'Brain distribution of carboxy terminus of Hsc70-interacting protein (CHIP) and its nuclear translocation in cultured cortical neurons following heat stress or oxygen-glucose deprivation.'
  findings: []
- id: PMID:20029029
  title: Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6.
  findings: []
- id: PMID:20588253
  title: 'CHIP-dependent termination of MEKK2 regulates temporal ERK activation required for proper hyperosmotic response.'
  findings: []
- id: PMID:20618441
  title: CHIP participates in protein triage decisions by preferentially ubiquitinating Hsp70-bound substrates.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches PubMed; establishes CHIP/STUB1's protein-quality-control triage role - preferentially ubiquitinating misfolded chaperone substrates for degradation, a core function.
- id: PMID:20724525
  title: 'Novel role of C terminus of Hsc70-interacting protein (CHIP) ubiquitin ligase on inhibiting cardiac apoptosis and dysfunction via regulating ERK5-mediated degradation of inducible cAMP early repressor.'
  findings: []
- id: PMID:21044950
  title: Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.
  findings: []
- id: PMID:21358815
  title: 'Ubiquitinylation of α-synuclein by carboxyl terminus Hsp70-interacting protein (CHIP) is regulated by Bcl-2-associated athanogene 5 (BAG5).'
  findings: []
- id: PMID:21360678
  title: Label-free quantitative proteomics and SAINT analysis enable interactome mapping for the human Ser/Thr protein phosphatase 5.
  findings: []
- id: PMID:22190034
  title: Global landscape of HIV-human protein complexes.
  findings: []
- id: PMID:22366786
  title: Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy.
  findings: []
- id: PMID:23431407
  title: Distinct roles of molecular chaperones HSP90α and HSP90β in the biogenesis of KCNQ4 channels.
  findings: []
- id: PMID:23973223
  title: 'The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3.'
  findings: []
- id: PMID:23990462
  title: 'Endoplasmic reticulum protein quality control is determined by cooperative interactions between Hsp/c70 protein and the CHIP E3 ligase.'
  findings: []
- id: PMID:24043303
  title: 'The ubiquitin ligase CHIP prevents SirT6 degradation through noncanonical ubiquitination.'
  findings: []
- id: PMID:24510904
  title: Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease.
  findings: []
- id: PMID:24613385
  title: Hsp70 and Hsp90 oppositely regulate TGF-β signaling through CHIP/Stub1.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: GOA-anchored (this PMID supports GO:0061630 ubiquitin protein ligase activity IDA, GO:0030544 Hsp70 protein binding IPI, and GO:0043161 proteasome-mediated degradation in STUB1-goa.tsv); directly establishes all three CHIP/STUB1 core functions - E3 ligase activity, Hsp70 co-chaperone binding, and chaperone-coupled proteasomal degradation.
- id: PMID:24658140
  title: The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells.
  findings: []
- id: PMID:24981860
  title: Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.
  findings: []
- id: PMID:25036637
  title: A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways.
  findings: []
- id: PMID:25260751
  title: The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines.
  findings: []
- id: PMID:25277244
  title: The functional landscape of Hsp27 reveals new cellular processes such as DNA repair and alternative splicing and proposes novel anticancer targets.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:26265139
  title: UBXN2A regulates nicotinic receptor degradation by modulating the E3 ligase activity of CHIP.
  findings: []
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
  findings: []
- id: PMID:26634371
  title: Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy.
  findings: []
- id: PMID:26871637
  title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
  findings: []
- id: PMID:27353360
  title: The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding.
  findings: []
- id: PMID:27708256
  title: ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation.
  findings: []
- id: PMID:28386764
  title: Roles of tau protein in health and disease.
  findings: []
- id: PMID:29513927
  title: Comparative Protein Interaction Network Analysis Identifies Shared and Distinct Functions for the Human ROCO Proteins.
  findings: []
- id: PMID:29568061
  title: An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.
  findings: []
- id: PMID:29883609
  title: 'PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylation-Dependent Proteasomal Degradation.'
  findings: []
- id: PMID:31046837
  title: Parkinson's disease-associated LRRK2-G2019S mutant acts through regulation of SERCA activity to control ER stress in astrocytes.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
  findings: []
- id: PMID:31980649
  title: Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32707033
  title: Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:35266954
  title: The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.
  findings: []
- id: PMID:37045861
  title: Interactome dynamics of RAF1-BRAF kinase monomers and dimers.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: Reactome:R-HSA-1227986
  title: Reactome pathway R-HSA-1227986
  findings: []
- id: Reactome:R-HSA-1918092
  title: Reactome pathway R-HSA-1918092
  findings: []
- id: Reactome:R-HSA-2173788
  title: Reactome pathway R-HSA-2173788
  findings: []
- id: Reactome:R-HSA-2187368
  title: Reactome pathway R-HSA-2187368
  findings: []
- id: Reactome:R-HSA-2187375
  title: Reactome pathway R-HSA-2187375
  findings: []
- id: Reactome:R-HSA-6807134
  title: Reactome pathway R-HSA-6807134
  findings: []
- id: Reactome:R-HSA-9009308
  title: Reactome pathway R-HSA-9009308
  findings: []
- id: Reactome:R-HSA-9009309
  title: Reactome pathway R-HSA-9009309
  findings: []
- id: Reactome:R-HSA-9688831
  title: Reactome pathway R-HSA-9688831
  findings: []
- id: Reactome:R-HSA-9688838
  title: Reactome pathway R-HSA-9688838
  findings: []
- id: Reactome:R-HSA-9796368
  title: Reactome pathway R-HSA-9796368
  findings: []
- id: Reactome:R-HSA-9796387
  title: Reactome pathway R-HSA-9796387
  findings: []
core_functions:
- description: U-box-type E3 ubiquitin-protein ligase that, in cooperation with E2 enzymes, ubiquitinates chaperone-bound misfolded/damaged client proteins and targets them for proteasomal degradation.
  molecular_function:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/STUB1/STUB1-uniprot.txt
    supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
- description: 'HSP70/HSC70/HSP90 co-chaperone: via its TPR domain CHIP binds these chaperones and modulates their activity, coupling client triage to the chaperone cycle.'
  molecular_function:
    id: GO:0030544
    label: Hsp70 protein binding
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/STUB1/STUB1-uniprot.txt
    supporting_text: chaperone complexes, including Hsp70, Hsc70 and Hsp90
- description: 'Protein quality control: CHIP recognizes misfolded chaperone substrates and routes them to ubiquitin-dependent proteasomal degradation, integrating folding and degradation decisions.'
  molecular_function:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/STUB1/STUB1-uniprot.txt
    supporting_text: E3 ubiquitin-protein ligase which targets misfolded chaperone
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: 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)?
- question: 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?
suggested_experiments:
- description: 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.
- description: 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.
- description: Quantify CHIP homodimerization and its requirement for E3 activity using engineered monomeric variants, correlating with chaperone binding and substrate turnover.