id: P31948
gene_symbol: STIP1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: STIP1 (stress-induced phosphoprotein 1), better known as HOP (Hsp70-Hsp90 organizing protein) or p60, is a cytoplasmic (and partly nuclear) TPR-domain adaptor co-chaperone. It contains three TPR (tetratricopeptide repeat) domains. The TPR1 domain binds the C-terminal EEVD motif of HSP70 (HSPA8/HSC70), while the TPR2A and TPR2B domains bind the C-terminal MEEVD motif of HSP90. By simultaneously engaging both chaperones, HOP physically bridges the HSP70 and HSP90 systems and coordinates the transfer of client proteins from HSP70 to HSP90 during the chaperone cycle. HOP has no catalytic activity; it functions as a scaffold/adaptor that modulates HSP90 conformation and client maturation. It is a defining component of the HSP70-HSP90 multichaperone machine and participates in the maturation of diverse clients including protein kinases and steroid hormone receptors.
alternative_products:
- name: '1'
  id: P31948-1
- name: '2'
  id: P31948-2
  sequence_note: VSP_055034
- name: '3'
  id: P31948-3
  sequence_note: VSP_055035
existing_annotations:
- term:
    id: GO:0051879
    label: Hsp90 protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: HOP binds HSP90 directly via its TPR2A/TPR2B domains (HSP90 C-terminal MEEVD). This is a core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION/DOMAIN and by experimental HSP90 interaction data; HSP90 binding is central to HOP's adaptor role.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: The TPR 4, 5 and 6 repeats (also called TPR2A domain) and TPR 7, 8 and 9 repeats (also called TPR2B domain) interact with HSP90.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: HOP is detected in the nucleus in addition to the cytoplasm; nuclear shuttling is documented.
    action: KEEP_AS_NON_CORE
    reason: UniProt lists Nucleus as a subcellular location; nuclear pool is real but HOP's principal chaperone-organizing function is cytoplasmic.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: HOP is predominantly cytoplasmic, where it organizes the HSP70-HSP90 machine.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm is the genuine principal compartment of HOP.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0120293
    label: dynein axonemal particle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: By-similarity localization to the dynein axonemal particle, reflecting a role of HOP/co-chaperones in cytoplasmic preassembly of axonemal dynein in ciliated cells.
    action: KEEP_AS_NON_CORE
    reason: Specialized, by-similarity localization in ciliated-cell contexts; peripheral to HOP's general cytoplasmic chaperone-organizing function.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: Dynein axonemal particle
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20029029
  qualifier: enables
  review:
    summary: Interaction with EGFR (P00533), an HSP90 client kinase. Bare protein binding is uninformative; the interaction is consistent with HOP's role in client maturation but is a generic binding term.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction with an HSP90 client (EGFR), but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21044950
  qualifier: enables
  review:
    summary: High-throughput interaction (partner Q96AP0). Bare protein binding is uninformative and the partner is not part of HOP's core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction but bare protein binding is uninformative; not core.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21170051
  qualifier: enables
  review:
    summary: Interaction with HSP90AB1 (P08238). Bare protein binding is uninformative; this HSP90 interaction is better captured as Hsp90 protein binding.
    action: MODIFY
    reason: The WITH partner is HSP90AB1 (P08238); the interaction is precisely captured as Hsp90 protein binding, a core HOP function.
    proposed_replacement_terms:
    - id: GO:0051879
      label: Hsp90 protein binding
    supported_by:
    - reference_id: file:human/STIP1/STIP1-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 PPP5C (P53041), a TPR-domain HSP90 co-chaperone phosphatase. Bare protein binding is uninformative; the partner is chaperone-machinery-related.
    action: KEEP_AS_NON_CORE
    reason: Real interaction with a co-chaperone (PPP5C) within the HSP90 machine, but bare protein binding is uninformative; not elevated to core.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-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: Quantitative chaperone interaction network capturing HOP with HSP90AB1 (P08238) and CDC37L1 (Q7L3B6) among others. Bare protein binding is uninformative; the meaningful partner is HSP90.
    action: MODIFY
    reason: WITH partners include HSP90AB1 (P08238); the chaperone-network interaction is precisely captured as Hsp90 protein binding.
    proposed_replacement_terms:
    - id: GO:0051879
      label: Hsp90 protein binding
    supported_by:
    - reference_id: file:human/STIP1/STIP1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28330616
  qualifier: enables
  review:
    summary: Interaction with PPP5C (P53041), an HSP90 co-chaperone. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction with a chaperone-machinery component but uninformative protein binding term; not core.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Binary interactome capturing HOP with HSP90AB1 (P08238) and another partner. Bare protein binding is uninformative; the meaningful partner is HSP90.
    action: MODIFY
    reason: WITH partner HSP90AB1 (P08238); precisely captured as Hsp90 protein binding.
    proposed_replacement_terms:
    - id: GO:0051879
      label: Hsp90 protein binding
    supported_by:
    - reference_id: file:human/STIP1/STIP1-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: Interaction with EGFR (P00533) and ERBB2 (P04626), HSP90 client kinases. Bare protein binding is uninformative; consistent with HOP's client-maturation role.
    action: KEEP_AS_NON_CORE
    reason: Records real interactions with HSP90 client kinases, but bare protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-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: Large neurodegeneration interactome capturing many partners (e.g. MYC, p53), none being core chaperones. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome partners unrelated to HOP's chaperone-organizing function; uninformative protein binding.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-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: BioPlex interactome capturing HOP interactions (partners O15484, Q8IWD4). Bare protein binding is uninformative and these are not core chaperone partners.
    action: KEEP_AS_NON_CORE
    reason: Records real high-throughput interactions but uninformative protein binding; not core.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35140242
  qualifier: enables
  review:
    summary: Interaction with p53 (P04637). Bare protein binding is uninformative; p53 is an HSP90 client but this is a generic binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction with an HSP90 client (p53), but bare protein binding is uninformative; not core.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Chaperome interaction-landscape study capturing HOP with HSP90AB1 (P08238). Bare protein binding is uninformative; the meaningful partner is HSP90.
    action: MODIFY
    reason: WITH partner HSP90AB1 (P08238); precisely captured as Hsp90 protein binding.
    proposed_replacement_terms:
    - id: GO:0051879
      label: Hsp90 protein binding
    supported_by:
    - reference_id: file:human/STIP1/STIP1-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: Multimodal cell-maps interactome (partner Q8IWD4). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real high-throughput interaction but uninformative protein binding; not core.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-goa.tsv
      supporting_text: GO:0005515 protein binding
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence-similarity-based nuclear localization, consistent with HOP's documented nuclear pool.
    action: KEEP_AS_NON_CORE
    reason: Consistent with UniProt Nucleus location; nuclear pool is real but non-core relative to the cytoplasmic chaperone-organizing role.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence-similarity-based cytoplasm localization, consistent with HOP's principal compartment.
    action: ACCEPT
    reason: Matches UniProt subcellular location; cytoplasm is the genuine principal compartment.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0120293
    label: dynein axonemal particle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence-similarity-based localization to the dynein axonemal particle (ciliated-cell dynein preassembly context).
    action: KEEP_AS_NON_CORE
    reason: Specialized by-similarity localization; peripheral to HOP's general chaperone-organizing function.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: Dynein axonemal particle
- term:
    id: GO:0051879
    label: Hsp90 protein binding
  evidence_type: IPI
  original_reference_id: PMID:29127155
  qualifier: enables
  review:
    summary: Experimental evidence for HOP binding HSP90 within the HSP70-HSP90 multichaperone complex. Core molecular function.
    action: ACCEPT
    reason: Directly supported; HOP is a defining HSP90-binding component of the multichaperone machine described in this study and in UniProt SUBUNIT.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2
- term:
    id: GO:0101031
    label: protein folding chaperone complex
  evidence_type: IDA
  original_reference_id: PMID:29127155
  qualifier: part_of
  review:
    summary: HOP is part of the HSP70-HSP90 multichaperone complex, a folding chaperone complex. This is an accurate and core complex annotation.
    action: ACCEPT
    reason: Directly supported by UniProt SUBUNIT (HSP90/HSP70/STIP1/CDC37/PPP5C/p23/TSC1 complex); HOP is a defining organizing subunit.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23349634
  qualifier: enables
  review:
    summary: Interaction with the lysine methyltransferase EEF1AKMT3 (Q96AZ1). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction but bare protein binding is uninformative; not core.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: Interacts with EEF1AKMT3
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:23349634
  qualifier: part_of
  review:
    summary: Generic protein-containing complex annotation from a methyltransferase study. Less informative than the specific HSP70-HSP90 multichaperone complex term.
    action: KEEP_AS_NON_CORE
    reason: Generic complex term; the informative complex annotation is GO:0101031 (HSP70-HSP90 multichaperone complex).
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: Interacts with EEF1AKMT3
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24880080
  qualifier: enables
  review:
    summary: Interaction with HSP90AB1 (P08238), modulated by SMYD2-dependent HSP90AB1 methylation. Bare protein binding is uninformative; the meaningful partner is HSP90.
    action: MODIFY
    reason: WITH partner HSP90AB1 (P08238); precisely captured as Hsp90 protein binding.
    proposed_replacement_terms:
    - id: GO:0051879
      label: Hsp90 protein binding
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: Interacts with HSP90AB1; upon SMYD2-dependent HSP90AB1 methylation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23431407
  qualifier: enables
  review:
    summary: Interaction with partner P56696. Bare protein binding is uninformative and not part of HOP's core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction but bare protein binding is uninformative; not core.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-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 HSP90AA1 (P07900) and the FLCN/FNIP co-chaperone module. Bare protein binding is uninformative; the meaningful partner is HSP90.
    action: MODIFY
    reason: WITH partner HSP90AA1 (P07900); precisely captured as Hsp90 protein binding, a core HOP function.
    proposed_replacement_terms:
    - id: GO:0051879
      label: Hsp90 protein binding
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: Acts as a co-chaperone for HSP90AA1
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3371503
  qualifier: located_in
  review:
    summary: Curated (Reactome) cytosolic localization, consistent with HOP's cytoplasmic chaperone role.
    action: ACCEPT
    reason: Cytosol is the genuine principal compartment of HOP; consistent with UniProt.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5618085
  qualifier: located_in
  review:
    summary: Curated (Reactome) cytosolic localization, consistent with HOP's cytoplasmic chaperone role.
    action: ACCEPT
    reason: Cytosol is the genuine principal compartment of HOP; consistent with UniProt (one of several redundant Reactome cytosol annotations).
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5618098
  qualifier: located_in
  review:
    summary: Curated (Reactome) cytosolic localization, consistent with HOP's cytoplasmic chaperone role.
    action: ACCEPT
    reason: Cytosol is the genuine principal compartment of HOP; consistent with UniProt (one of several redundant Reactome cytosol annotations).
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5618105
  qualifier: located_in
  review:
    summary: Curated (Reactome) cytosolic localization, consistent with HOP's cytoplasmic chaperone role.
    action: ACCEPT
    reason: Cytosol is the genuine principal compartment of HOP; consistent with UniProt (one of several redundant Reactome cytosol annotations).
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5618107
  qualifier: located_in
  review:
    summary: Curated (Reactome) cytosolic localization, consistent with HOP's cytoplasmic chaperone role.
    action: ACCEPT
    reason: Cytosol is the genuine principal compartment of HOP; consistent with UniProt (one of several redundant Reactome cytosol annotations).
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5618110
  qualifier: located_in
  review:
    summary: Curated (Reactome) cytosolic localization, consistent with HOP's cytoplasmic chaperone role.
    action: ACCEPT
    reason: Cytosol is the genuine principal compartment of HOP; consistent with UniProt (one of several redundant Reactome cytosol annotations).
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9696271
  qualifier: located_in
  review:
    summary: Curated (Reactome) cytosolic localization, consistent with HOP's cytoplasmic chaperone role.
    action: ACCEPT
    reason: Cytosol is the genuine principal compartment of HOP; consistent with UniProt (one of several redundant Reactome cytosol annotations).
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: mRNA-interactome-capture detection of HOP as an RNA-binder. No characterized RNA-dependent function for HOP exists.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput RNA-interactome capture without a validated functional role; not part of HOP's chaperone-organizing function.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-goa.tsv
      supporting_text: GO:0003723 RNA binding
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: TAS
  original_reference_id: PMID:16130169
  qualifier: located_in
  review:
    summary: Curated nuclear localization of HOP, consistent with its documented nuclear pool.
    action: KEEP_AS_NON_CORE
    reason: Nuclear pool is real (UniProt lists Nucleus) but non-core relative to the cytoplasmic chaperone-organizing role.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: TAS
  original_reference_id: PMID:1569099
  qualifier: located_in
  review:
    summary: Early curated nuclear localization of HOP/p60.
    action: KEEP_AS_NON_CORE
    reason: Consistent with the documented nuclear pool; non-core relative to the cytoplasmic function.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: TAS
  original_reference_id: PMID:1569099
  qualifier: located_in
  review:
    summary: Early curated Golgi localization of HOP/p60. Not corroborated by the current UniProt subcellular-location record (cytoplasm/nucleus/dynein axonemal particle).
    action: KEEP_AS_NON_CORE
    reason: Historical localization not supported as a principal compartment in current UniProt; peripheral to HOP's cytoplasmic chaperone function.
    supported_by:
    - reference_id: file:human/STIP1/STIP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
references:
- 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:0000044
  title: Gene Ontology annotation based on UniProtKB Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:1569099
  title: 'Molecular cloning and expression of a transformation-sensitive human protein containing the TPR motif and sharing identity to the stress-inducible yeast protein STI1.'
  findings: []
- id: PMID:16130169
  title: Proteomics of human umbilical vein endothelial cells applied to etoposide-induced apoptosis.
  findings: []
- id: PMID:20029029
  title: Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6.
  findings: []
- id: PMID:21044950
  title: Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.
  findings: []
- id: PMID:21170051
  title: Mixed Hsp90-cochaperone complexes are important for the progression of the reaction cycle.
  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:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
- id: PMID:23349634
  title: A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity.
  findings:
  - statement: HOP/STIP1 interacts with the methyltransferase EEF1AKMT3.
    reference_section_type: RESULTS
- id: PMID:23431407
  title: Distinct roles of molecular chaperones HSP90α and HSP90β in the biogenesis of KCNQ4 channels.
  findings: []
- id: PMID:24880080
  title: SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by regulating the chaperone complex formation.
  findings: []
- id: PMID:25036637
  title: A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways.
  findings:
  - statement: HOP/STIP1 is a hub co-chaperone within the HSP90 module, interacting with HSP90AA1/HSP90AB1.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches PubMed; the quantitative chaperone-interaction network places HOP/STIP1 as a hub co-chaperone of the HSP90 module interacting with HSP90AA1/HSP90AB1, supporting its core Hsp70-Hsp90 organizing/adaptor function (GO:0051879).
- id: PMID:27353360
  title: The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding.
  findings:
  - statement: HOP/STIP1 acts as a co-chaperone for HSP90AA1; its interaction with HSP90 modulates the chaperone cycle.
    reference_section_type: RESULTS
- id: PMID:28330616
  title: Systematic Analysis of Human Protein Phosphatase Interactions and Dynamics.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:29127155
  title: Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients.
  findings:
  - statement: HOP/STIP1 is a component of the HSP70-HSP90 multichaperone complex (with CDC37, PPP5C, p23, TSC1) that matures kinase and non-kinase clients.
    reference_section_type: RESULTS
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: GOA-anchored (this PMID supports GO:0051879 Hsp90 protein binding, IPI, and GO:0101031 chaperone complex in STIP1-goa.tsv); corroborates STIP1/HOP as a component of the HSP70-HSP90 multichaperone machine maturing kinase/non-kinase clients.
- id: PMID:31980649
  title: Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
  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:35140242
  title: Human transcription factor protein interaction networks.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: Reactome:R-HSA-3371503
  title: HSF1 activation / cytosolic chaperone pathway
  findings: []
- id: Reactome:R-HSA-5618085
  title: Cytosolic chaperone (HSP90) pathway
  findings: []
- id: Reactome:R-HSA-5618098
  title: Cytosolic chaperone (HSP90) pathway
  findings: []
- id: Reactome:R-HSA-5618105
  title: Cytosolic chaperone (HSP90) pathway
  findings: []
- id: Reactome:R-HSA-5618107
  title: Cytosolic chaperone (HSP90) pathway
  findings: []
- id: Reactome:R-HSA-5618110
  title: Cytosolic chaperone (HSP90) pathway
  findings: []
- id: Reactome:R-HSA-9696271
  title: Cytosolic chaperone (HSP90) pathway
  findings: []
- id: file:human/STIP1/STIP1-uniprot.txt
  title: UniProt entry P31948 (STIP1_HUMAN), stress-induced phosphoprotein 1 / HOP
  findings:
  - statement: HOP/STIP1 is a TPR-domain co-chaperone that mediates the association of HSC70/HSPA8 and HSP90; TPR1 binds HSC70 and TPR2A/TPR2B bind HSP90; it is part of the HSP70-HSP90 multichaperone complex and is cytoplasmic/nuclear.
    reference_section_type: OTHER
core_functions:
- description: Hsp70-Hsp90 organizing protein (HOP); a TPR-domain adaptor co-chaperone that binds HSP90 (via TPR2A/TPR2B) and bridges it to HSP70/HSC70 (via TPR1), coordinating transfer of client proteins from HSP70 to HSP90.
  molecular_function:
    id: GO:0051879
    label: Hsp90 protein binding
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/STIP1/STIP1-uniprot.txt
    supporting_text: Mediates the association of the molecular chaperones HSPA8/HSC70 and HSP90
  - reference_id: file:human/STIP1/STIP1-uniprot.txt
    supporting_text: The TPR 4, 5 and 6 repeats (also called TPR2A domain) and TPR 7, 8 and 9 repeats (also called TPR2B domain) interact with HSP90.
- description: Component of the HSP70-HSP90 multichaperone machine that organizes client maturation; HOP acts as a scaffold without catalytic activity, holding HSP90 in a client-loading-competent state.
  molecular_function:
    id: GO:0051879
    label: Hsp90 protein binding
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/STIP1/STIP1-uniprot.txt
    supporting_text: Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2
  in_complex:
    id: GO:0101031
    label: protein folding chaperone complex
proposed_new_terms: []
suggested_questions:
- question: How is the HOP-mediated HSP70-to-HSP90 client handoff regulated in human cells, and is HOP strictly required or can clients transfer via HOP-independent routes (as suggested in some organisms)?
- question: What determines the cytoplasmic versus nuclear partitioning of HOP, and does the nuclear pool have a chaperone-independent function?
- question: Do the alternative HOP isoforms (P31948-2, P31948-3) differ in TPR-domain composition and thus in HSP70/HSP90 binding or client specificity?
suggested_experiments:
- description: Reconstitute the HSP70-HOP-HSP90 client-transfer reaction in vitro with a model client (e.g. a kinase or steroid receptor) and TPR-domain point mutants to dissect the HSP70-binding (TPR1) versus HSP90-binding (TPR2A/2B) contributions to handoff.
- description: HOP knockout/knockdown followed by client stability profiling (kinases, steroid receptors) to quantify HOP dependence of the HSP90 clientele in human cells.
- description: Crosslinking-MS or cryo-EM of the human HSP70-HOP-HSP90 intermediate to define the architecture of the client-loading complex.