YDJ1

id: P25491
gene_symbol: YDJ1
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: >-
  YDJ1 (also known as MAS5) is a Type I Hsp40/DnaJ co-chaperone that functions as a key
  regulator of Hsp70 (Ssa1) chaperone activity in S. cerevisiae. It stimulates the ATPase
  activity of Ssa1 and delivers substrate proteins to the Hsp70 machinery for folding.
  YDJ1 contains a J-domain (residues 4-72) that interacts with Hsp70 to stimulate ATPase
  activity, a zinc finger-like cysteine-rich region (residues 130-213) that contributes to
  substrate recognition, and a C-terminal peptide-binding domain. YDJ1 functions in protein
  refolding (with Hsp104/Hsp70), de novo protein folding, ERAD, protein targeting to the ER,
  and regulation of the HAP1 transcription factor in response to heme/oxygen levels. It is
  farnesylated at Cys-406 and localized primarily to the cytosol and perinuclear region.
existing_annotations:
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA annotation for cytosol localization is well supported. YDJ1 was shown by
      immunofluorescence to localize to the cytoplasm and perinuclear region (PMID:1869583),
      and confirmed by large-scale HDA studies (PMID:26928762) and IDA (PMID:8144572).
    action: ACCEPT
    reason: >-
      Cytosol is a well-established localization for YDJ1. Multiple independent methods
      confirm cytosolic localization. IBA is consistent with IDA evidence from PMID:1869583
      and PMID:8144572.
- term:
    id: GO:0001671
    label: ATPase activator activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA annotation for ATPase activator activity is strongly supported. YDJ1 stimulates
      the ATPase activity of Hsp70 Ssa1 (PMID:1400408, PMID:9774392), which is the core
      molecular function of J-domain co-chaperones.
    action: ACCEPT
    reason: >-
      ATPase activator activity is the defining molecular function of the J-domain.
      Experimentally demonstrated by IDA (PMID:1400408, PMID:15342786) and conserved across
      the DnaJ family.
    supported_by:
      - reference_id: PMID:1400408
        supporting_text: >-
          We report that a purified cytoplasmic Hsp70 homolog from Saccharomyces cerevisiae,
          Hsp70SSA1, exhibits a weak ATPase activity, which is stimulated by a purified
          eukaryotic dnaJp homolog (YDJ1p).
      - reference_id: PMID:9774392
        supporting_text: >-
          This functional difference was explored and could not be accounted for by differences
          in the ability of Sis1 and Ydj1 to regulate Ssa1 ATPase activity.
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA annotation for cellular response to heat is appropriate. YDJ1 is a heat shock
      gene whose expression increases at elevated temperatures (UniProt). It participates
      in protein refolding after heat stress as part of the Hsp104/Hsp70/Hsp40 chaperone
      system (PMID:9674429). Also supported by IMP evidence (PMID:25344756).
    action: ACCEPT
    reason: >-
      YDJ1 is a bona fide heat shock protein involved in stress response. IBA is consistent
      with IMP evidence and the well-established role of Hsp40 in heat stress response.
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA annotation for protein refolding is well supported. Hsp104, Hsp70 (Ssa1), and
      Hsp40 (Ydj1) cooperate to refold aggregated proteins (PMID:9674429). YDJ1:Ssa1 can
      refold luciferase in vitro (PMID:9774392).
    action: ACCEPT
    reason: >-
      Protein refolding is a core biological process for YDJ1 as part of the
      Hsp104/Hsp70/Hsp40 disaggregation/refolding machinery. Confirmed by IDA (PMID:9674429).
    supported_by:
      - reference_id: PMID:9674429
        supporting_text: >-
          However, in concert with Hsp40 and Hsp70, Hsp104 can reactivate proteins that have
          been denatured and allowed to aggregate, substrates refractory to the action of
          other chaperones.
      - reference_id: PMID:9774392
        supporting_text: >-
          Ydj1 and Sis1 could both functionally interact with Ssa1, but not the Ssb1/2
          proteins, to refold luciferase. Interestingly, Ydj1:Ssa1 could promote up to four
          times more luciferase folding than Sis1:Ssa1.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GO:0051082 is proposed for obsoletion. YDJ1 does bind unfolded/denatured substrates
      via its C-terminal domain and zinc finger region (PMID:9774392), but its molecular
      function is more accurately described as protein folding chaperone activity
      (GO:0044183), since it actively participates in the folding process rather than
      merely binding unfolded proteins.
    action: MODIFY
    reason: >-
      GO:0051082 "unfolded protein binding" is proposed for obsoletion. YDJ1 is an active
      co-chaperone that delivers substrates to Hsp70 for folding. The replacement term
      GO:0044183 "protein folding chaperone" better captures the functional role of YDJ1.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
    supported_by:
      - reference_id: PMID:9774392
        supporting_text: >-
          Ydj1 was dramatically more effective than Sis1 at suppressing the thermally induced
          aggregation of luciferase. Paradoxically, Sis1 and Ydj1 could bind similar
          quantities of chemically denatured luciferase.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA annotation for nuclear localization. YDJ1 functions in the nucleus as part of
      the HMC complex regulating HAP1 transcription factor activity (PMID:15102838). Also
      involved in tRNA import into nucleus (PMID:25853343). Supported by NAS (PMID:15102838).
    action: ACCEPT
    reason: >-
      Nuclear localization is supported by its role in the HAP1 repressor complex and tRNA
      nuclear import. IBA is consistent with NAS evidence.
- term:
    id: GO:0001671
    label: ATPase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      IEA annotation for ATPase activator activity from ARBA machine learning. Consistent
      with IDA and IBA evidence for the same term.
    action: ACCEPT
    reason: >-
      Correct IEA annotation. ATPase activator activity is the core molecular function of
      YDJ1, confirmed by multiple experimental studies (PMID:1400408, PMID:15342786).
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation for ATP binding based on InterPro domain IPR012724 (DnaJ). While YDJ1
      stimulates the ATPase of Hsp70 and regulates substrate binding in an ATP-dependent
      manner, the ATP binding is a property of Hsp70 (Ssa1), not YDJ1 itself. YDJ1 does
      not have an intrinsic ATPase or ATP-binding domain.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      YDJ1 regulates Hsp70 ATPase activity but does not itself bind ATP. The InterPro
      mapping appears to be overly broad. The J-domain stimulates ATP hydrolysis by Hsp70
      but the DnaJ protein itself is not an ATPase or ATP-binding protein.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA annotation for cytoplasm based on UniProt subcellular location. Correct but
      less specific than cytosol (GO:0005829) which is supported by IDA evidence.
    action: ACCEPT
    reason: >-
      Cytoplasm is a correct broader localization, consistent with the more specific
      cytosol annotation. The IEA mapping from UniProt subcellular location is accurate.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation for protein folding from InterPro. YDJ1 participates in protein folding
      as a co-chaperone of Hsp70. This is accurate at the BP level.
    action: ACCEPT
    reason: >-
      Protein folding is a core biological process for YDJ1, supported by multiple
      experimental studies including its role in de novo protein folding (PMID:10567418)
      and protein refolding (PMID:9674429).
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      IEA annotation for zinc ion binding based on UniProt keyword. YDJ1 has a well-characterized
      zinc finger cysteine-rich domain (residues 130-213) with four CXXCXGXG repeats that
      coordinate two zinc ions. Supported by crystal structure (PMID:14656432).
    action: ACCEPT
    reason: >-
      Zinc binding is structurally confirmed. The zinc finger domain is essential for
      substrate recognition and chaperone function, distinguishing Type I from Type II
      Hsp40 proteins.
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation for response to heat. YDJ1 is a heat-inducible chaperone gene.
      This is a broader parent of the more specific IBA/IMP-supported cellular response
      to heat (GO:0034605).
    action: ACCEPT
    reason: >-
      Correct but less specific than GO:0034605. The IEA is consistent with the established
      role of YDJ1 as a heat shock protein.
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      IEA annotation for protein transport from UniProt keyword. YDJ1 is involved in
      protein targeting to the ER (PMID:1473150) and mitochondrial protein import, both
      of which involve protein transport.
    action: ACCEPT
    reason: >-
      Protein transport is a broad but accurate annotation. YDJ1 participates in
      translocation of pre-pro-alpha-factor (PMID:1473150) and was originally identified
      as MAS5 (mitochondrial assembly protein).
- term:
    id: GO:0030544
    label: Hsp70 protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation for Hsp70 protein binding from InterPro. YDJ1 physically interacts
      with Ssa1 (Hsp70) through its J-domain and functionally cooperates with it
      (PMID:1400408, PMID:9774392). Also interacts with Hsp82 (Hsp90).
    action: ACCEPT
    reason: >-
      Hsp70 binding is a core interaction for YDJ1 as a J-domain co-chaperone. However,
      this is a binding term and the functional relationship is better captured by
      GO:0001671 (ATPase activator activity). Acceptable as an IEA.
- term:
    id: GO:0031072
    label: heat shock protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation for heat shock protein binding from InterPro. YDJ1 binds Hsp70 (Ssa1)
      and Hsp90 (Hsp82). This is a broader parent of Hsp70 protein binding.
    action: ACCEPT
    reason: >-
      Correct but less specific than GO:0030544 (Hsp70 protein binding). Acceptable as
      a broad IEA annotation.
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      IEA annotation for metal ion binding from UniProt keyword. YDJ1 binds zinc ions via
      its cysteine-rich domain. This is a broader parent of GO:0008270 (zinc ion binding).
    action: ACCEPT
    reason: >-
      Correct but less specific than zinc ion binding. Acceptable as a broad IEA annotation.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA annotation for perinuclear region based on UniProt subcellular location.
      Consistent with IDA evidence from PMID:1869583 showing YDJ1 is concentrated in
      a perinuclear ring.
    action: ACCEPT
    reason: >-
      Correct annotation supported by experimental evidence. UniProt notes YDJ1 is
      concentrated in a perinuclear ring as well as in the cytoplasm.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation for unfolded protein binding from InterPro. Same issue as the IBA
      annotation for this term - GO:0051082 is proposed for obsoletion, and the functional
      activity is better described as protein folding chaperone (GO:0044183).
    action: MODIFY
    reason: >-
      GO:0051082 is proposed for obsoletion. YDJ1 is an active co-chaperone, not merely a
      passive binder of unfolded proteins. Should be replaced with GO:0044183.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11805837
  review:
    summary: >-
      IPI annotation for protein binding from large-scale mass spectrometry identification
      of protein complexes. IntAct records interactions with RAD3, RAD24, and CTR9.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding (GO:0005515) is uninformative. The relevant interactions are better
      captured by more specific terms like Hsp70 protein binding (GO:0030544) or
      protein-folding chaperone binding (GO:0051087). Large-scale studies often detect
      indirect associations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15879519
  review:
    summary: >-
      IPI annotation for protein binding from two-hybrid screen for Hsp90 interactors.
      IntAct records interaction with HSP82 (P02829).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. The YDJ1-Hsp90 interaction is functionally
      relevant (co-chaperone relationship) but better captured by heat shock protein
      binding (GO:0031072).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16429126
  review:
    summary: >-
      IPI annotation for protein binding from proteome survey. IntAct records interaction
      with RAD3.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative for a chaperone/co-chaperone protein that interacts
      with many substrates and partners.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17441508
  review:
    summary: >-
      IPI annotation for protein binding showing YDJ1 interaction with SGT2 and MDY2.
      These are components of the TRC/GET pathway for tail-anchored protein insertion.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. The interaction with SGT2 and MDY2 is functionally
      relevant to YDJ1's role in the TRC complex (GO:0072380) for tail-anchored protein
      targeting.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18833196
  review:
    summary: >-
      IPI annotation for protein binding showing interaction with SUP35 (Q7LKB1, a prion
      protein). Part of the Hsp104/Hsp70/Hsp40 system regulating prion formation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. The interaction with SUP35 reflects YDJ1's
      chaperone function in prion regulation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19536198
  review:
    summary: >-
      IPI annotation for protein binding from atlas of chaperone-protein interactions.
      IntAct records multiple interactions including HSP82, RAD3, SSA1, SSE1, and others.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative for a co-chaperone. The interactions with Ssa1
      (Hsp70) and Hsp82 (Hsp90) are better captured by specific binding terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23217712
  review:
    summary: >-
      IPI annotation for protein binding showing interaction with SSA1 (P10591).
      CDK-dependent phosphorylation of Hsp70 regulates G1 cyclin abundance.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. The Ssa1 interaction is the core functional
      partnership of YDJ1 as a J-domain co-chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37968396
  review:
    summary: >-
      IPI annotation for protein binding from social and structural architecture of yeast
      protein interactome. IntAct records interactions with TIF2, EFT2, and SSE1.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative for a co-chaperone that interacts broadly with
      substrates and partner chaperones.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:15102838
  review:
    summary: >-
      NAS annotation for nuclear localization from ComplexPortal, based on YDJ1 function
      in the HMC complex that regulates HAP1 transcription factor (PMID:15102838). YDJ1
      is part of the Hsp70-Ydj1 complex that represses HAP1 activity in the absence of heme.
    action: ACCEPT
    reason: >-
      Nuclear localization is supported by YDJ1's role in the HAP1 repressor complex.
      Consistent with IBA evidence for the same term.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: NAS
  original_reference_id: PMID:15102838
  review:
    summary: >-
      NAS annotation from ComplexPortal. YDJ1 is part of the HMC complex that represses
      HAP1 transcriptional activity in the absence of heme (PMID:15102838, PMID:11689685).
    action: KEEP_AS_NON_CORE
    reason: >-
      YDJ1 participates in transcriptional repression of HAP1 as part of the Hsp70-Ydj1
      chaperone complex, but this is a secondary function. The primary role of YDJ1 is as
      a co-chaperone, and the transcriptional regulatory effect is a consequence of its
      chaperoning of HAP1.
- term:
    id: GO:0070482
    label: response to oxygen levels
  evidence_type: NAS
  original_reference_id: PMID:15102838
  review:
    summary: >-
      NAS annotation from ComplexPortal. YDJ1 mediates heme-dependent regulation of HAP1,
      which is a heme-responsive transcription factor that senses oxygen/heme levels
      (PMID:15102838).
    action: KEEP_AS_NON_CORE
    reason: >-
      YDJ1's role in oxygen response is indirect, through its chaperone function in the
      HAP1 regulatory complex. It is not an oxygen sensor itself.
- term:
    id: GO:0070482
    label: response to oxygen levels
  evidence_type: NAS
  original_reference_id: PMID:9632766
  review:
    summary: >-
      NAS annotation from ComplexPortal. Same biological role as above - YDJ1 participates
      in the higher-order complex mediating heme regulation of HAP1 (PMID:9632766).
    action: KEEP_AS_NON_CORE
    reason: >-
      Duplicate biological process annotation with different reference. YDJ1's role in
      oxygen response is through the HAP1 chaperone complex, not a direct sensory function.
- term:
    id: GO:0009267
    label: cellular response to starvation
  evidence_type: IMP
  original_reference_id: PMID:25853343
  review:
    summary: >-
      IMP annotation for cellular response to starvation. PMID:25853343 describes YDJ1's
      role in tRNA import into the nucleus, which is involved in the starvation response.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cellular response to starvation is a downstream phenotypic consequence of YDJ1's
      co-chaperone function in tRNA nuclear import. Not a core function of YDJ1.
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: IMP
  original_reference_id: PMID:25344756
  review:
    summary: >-
      IMP annotation for cellular response to heat. YDJ1 is a heat-inducible co-chaperone
      that participates in the heat stress response through protein refolding and
      quality control.
    action: ACCEPT
    reason: >-
      Cellular response to heat is a core biological process for YDJ1. It is induced by
      heat stress and functions in the Hsp104/Hsp70/Hsp40 refolding system.
- term:
    id: GO:0036503
    label: ERAD pathway
  evidence_type: IMP
  original_reference_id: PMID:15252059
  review:
    summary: >-
      IMP annotation for ERAD pathway. YDJ1 is required for efficient ERAD of both
      soluble luminal and multispanning membrane ERAD substrates (PMID:15252059).
    action: ACCEPT
    reason: >-
      ERAD is a well-documented function of YDJ1. As a cytosolic co-chaperone, YDJ1
      assists in the retrotranslocation and degradation of misfolded ER proteins.
- term:
    id: GO:0036503
    label: ERAD pathway
  evidence_type: IMP
  original_reference_id: PMID:15342786
  review:
    summary: >-
      IMP annotation for ERAD pathway. YDJ1 plays distinct roles from Hsp90 in CFTR
      degradation in yeast (PMID:15342786). YDJ1 stimulates Ssa1 ATPase activity to
      promote CFTR degradation.
    action: ACCEPT
    reason: >-
      Additional evidence supporting YDJ1's role in ERAD, specifically for CFTR
      degradation. Consistent with the other ERAD annotation.
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: RCA
  original_reference_id: PMID:30358795
  review:
    summary: >-
      RCA annotation for zinc ion binding from analysis of the yeast zinc proteome.
      Consistent with the known zinc finger domain (residues 130-213) with four
      CXXCXGXG repeats coordinating two Zn2+ ions.
    action: ACCEPT
    reason: >-
      Zinc binding is structurally confirmed by crystal structure (PMID:14656432).
      The RCA annotation is well supported.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: HDA
  original_reference_id: PMID:26928762
  review:
    summary: >-
      HDA annotation for cytosol localization from large-scale yeast library creation
      and analysis (PMID:26928762). Consistent with IDA evidence.
    action: ACCEPT
    reason: >-
      High-throughput data supporting cytosol localization. Consistent with targeted
      IDA studies (PMID:1869583, PMID:8144572).
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:25344756
  review:
    summary: >-
      IMP annotation for ubiquitin-dependent protein catabolic process. YDJ1 participates
      in ubiquitin-dependent degradation of misfolded or damaged proteins, particularly
      during heat stress.
    action: KEEP_AS_NON_CORE
    reason: >-
      YDJ1 facilitates ubiquitin-dependent degradation as part of its co-chaperone function
      in protein quality control. This is a downstream consequence of its chaperone activity
      rather than a direct enzymatic function.
- term:
    id: GO:0051131
    label: chaperone-mediated protein complex assembly
  evidence_type: IDA
  original_reference_id: PMID:10811660
  review:
    summary: >-
      IDA annotation for chaperone-mediated protein complex assembly. PMID:10811660 describes
      crystal structure and activity of human p23, an Hsp90 co-chaperone, but the annotation
      appears to be made in the context of YDJ1's role in the Hsp90 chaperone cycle for
      complex assembly.
    action: KEEP_AS_NON_CORE
    reason: >-
      YDJ1 can participate in chaperone-mediated complex assembly as part of the Hsp70/Hsp90
      chaperone machinery, but this is a secondary role. The primary reference is about
      human p23/Hsp90, not YDJ1 directly.
- term:
    id: GO:0035719
    label: tRNA import into nucleus
  evidence_type: IMP
  original_reference_id: PMID:25853343
  review:
    summary: >-
      IMP annotation for tRNA import into nucleus. Cytosolic Hsp70 and its co-chaperones
      (including YDJ1) constitute a novel system for tRNA import into the nucleus
      (PMID:25853343).
    action: KEEP_AS_NON_CORE
    reason: >-
      tRNA nuclear import is a specific function of the Hsp70-YDJ1 co-chaperone system
      but is not the core molecular function of YDJ1. It represents a specialized
      application of its general co-chaperone activity.
- term:
    id: GO:0001671
    label: ATPase activator activity
  evidence_type: IDA
  original_reference_id: PMID:1400408
  review:
    summary: >-
      IDA annotation for ATPase activator activity. This is the foundational paper
      demonstrating that YDJ1p stimulates the ATPase activity of Hsp70 Ssa1 (PMID:1400408).
    action: ACCEPT
    reason: >-
      Core molecular function of YDJ1, demonstrated by direct biochemical assay.
    supported_by:
      - reference_id: PMID:1400408
        supporting_text: >-
          We report that a purified cytoplasmic Hsp70 homolog from Saccharomyces cerevisiae,
          Hsp70SSA1, exhibits a weak ATPase activity, which is stimulated by a purified
          eukaryotic dnaJp homolog (YDJ1p).
- term:
    id: GO:0001671
    label: ATPase activator activity
  evidence_type: IDA
  original_reference_id: PMID:15342786
  review:
    summary: >-
      IDA annotation for ATPase activator activity from study of Hsp40/Hsp90 roles in
      CFTR degradation. YDJ1 stimulates Ssa1 ATPase activity in the context of ERAD.
    action: ACCEPT
    reason: >-
      Additional experimental evidence confirming ATPase activator activity, the core
      molecular function of YDJ1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:1869583
  review:
    summary: >-
      IDA annotation for cytosol localization from the original characterization of YDJ1
      by immunofluorescence (PMID:1869583).
    action: ACCEPT
    reason: >-
      Primary experimental evidence for cytosol localization from the founding
      characterization paper.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:8144572
  review:
    summary: >-
      IDA annotation for cytosol localization from differential regulation study of Hsp70
      subfamilies by YDJ1 (PMID:8144572).
    action: ACCEPT
    reason: >-
      Additional experimental evidence for cytosol localization.
- term:
    id: GO:0006458
    label: "'de novo' protein folding"
  evidence_type: IMP
  original_reference_id: PMID:10567418
  review:
    summary: >-
      IMP annotation for de novo protein folding. Mutations in YDJ1 cause defects in Axl1
      biogenesis and pro-alpha-factor processing (PMID:10567418), indicating a role in
      de novo folding of newly synthesized proteins.
    action: ACCEPT
    reason: >-
      De novo protein folding is a core biological process for YDJ1. As a co-chaperone of
      Hsp70, YDJ1 assists in folding newly synthesized polypeptides.
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IDA
  original_reference_id: PMID:9674429
  review:
    summary: >-
      IDA annotation for protein refolding. Hsp104, Hsp70, and Hsp40 (YDJ1) cooperate to
      rescue previously aggregated proteins (PMID:9674429).
    action: ACCEPT
    reason: >-
      Protein refolding is a core biological process for YDJ1. Direct assay evidence from
      the landmark Glover and Lindquist paper.
    supported_by:
      - reference_id: PMID:9674429
        supporting_text: >-
          However, in concert with Hsp40 and Hsp70, Hsp104 can reactivate proteins that have
          been denatured and allowed to aggregate, substrates refractory to the action of
          other chaperones.
- term:
    id: GO:0045047
    label: protein targeting to ER
  evidence_type: IMP
  original_reference_id: PMID:1473150
  review:
    summary: >-
      IMP annotation for protein targeting to ER. YDJ1 is required for efficient
      translocation of pre-pro-alpha-factor across the ER membrane (PMID:1473150).
    action: ACCEPT
    reason: >-
      Protein targeting to ER is a well-established function of YDJ1, originally identified
      through its role in maintaining translocation competence of precursor proteins.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:1869583
  review:
    summary: >-
      IDA annotation for perinuclear region of cytoplasm. YDJ1 is concentrated in a
      perinuclear ring by immunofluorescence (PMID:1869583).
    action: ACCEPT
    reason: >-
      Primary experimental evidence for perinuclear localization from the founding
      characterization paper.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:9774392
  review:
    summary: >-
      IDA annotation for unfolded protein binding based on direct binding assays showing
      YDJ1 binds chemically denatured luciferase (PMID:9774392). However, GO:0051082 is
      proposed for obsoletion and the functional role of YDJ1 is better described as
      protein folding chaperone activity.
    action: MODIFY
    reason: >-
      GO:0051082 is proposed for obsoletion. While YDJ1 does bind denatured proteins,
      this binding is in the context of its chaperone activity. The replacement term
      GO:0044183 "protein folding chaperone" better describes the function.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
    supported_by:
      - reference_id: PMID:9774392
        supporting_text: >-
          Ydj1 was dramatically more effective than Sis1 at suppressing the thermally induced
          aggregation of luciferase. Paradoxically, Sis1 and Ydj1 could bind similar
          quantities of chemically denatured luciferase.
- term:
    id: GO:0072380
    label: TRC complex
  evidence_type: IDA
  original_reference_id: PMID:20850366
  review:
    summary: >-
      IDA annotation for TRC complex membership. YDJ1 is part of a chaperone cascade that
      sorts proteins for post-translational membrane insertion into the ER via the TRC/GET
      pathway (PMID:20850366).
    action: ACCEPT
    reason: >-
      Membership in the TRC complex is experimentally demonstrated. This is a specific
      application of YDJ1's co-chaperone function in the tail-anchored protein insertion
      pathway.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:10567418
  title: Mutations in the yeast Hsp40 chaperone protein Ydj1 cause defects in Axl1 biogenesis and pro-a-factor processing.
  findings: []
- id: PMID:10811660
  title: Crystal structure and activity of human p23, a heat shock protein 90 co-chaperone.
  findings: []
- id: PMID:11689685
  title: The Hsp70-Ydj1 molecular chaperone represses the activity of the heme activator protein Hap1 in the absence of heme.
  findings: []
- id: PMID:11805837
  title: Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.
  findings: []
- id: PMID:1400408
  title: Regulation of Hsp70 function by a eukaryotic DnaJ homolog.
  findings:
    - statement: YDJ1p stimulates the ATPase activity of Hsp70 Ssa1
    - statement: YDJ1p regulates Hsp70 affinity for unfolded substrates in an ATP-dependent manner
- id: PMID:14656432
  title: The crystal structure of the yeast Hsp40 Ydj1 complexed with its peptide substrate.
  findings:
    - statement: Crystal structure of YDJ1 C-terminal domain (residues 103-350) with substrate analogs
    - statement: Zinc finger domain coordinates two Zn2+ ions
- id: PMID:1473150
  title: YDJ1p facilitates polypeptide translocation across different intracellular membranes by a conserved mechanism.
  findings: []
- id: PMID:15102838
  title: A novel mode of chaperone action - heme activation of Hap1 by enhanced association of Hsp90 with the repressed Hsp70-Hap1 complex.
  findings: []
- id: PMID:15252059
  title: Distinct machinery is required in Saccharomyces cerevisiae for the endoplasmic reticulum-associated degradation of a multispanning membrane protein and a soluble luminal protein.
  findings: []
- id: PMID:15342786
  title: Distinct roles for the Hsp40 and Hsp90 molecular chaperones during cystic fibrosis transmembrane conductance regulator degradation in yeast.
  findings: []
- id: PMID:15879519
  title: A two-hybrid screen of the yeast proteome for Hsp90 interactors uncovers a novel Hsp90 chaperone requirement in the activity of a stress-activated mitogen-activated protein kinase, Slt2p (Mpk1p).
  findings: []
- id: PMID:16429126
  title: Proteome survey reveals modularity of the yeast cell machinery.
  findings: []
- id: PMID:17441508
  title: SGT2 and MDY2 interact with molecular chaperone YDJ1 in Saccharomyces cerevisiae.
  findings: []
- id: PMID:1869583
  title: Characterization of YDJ1 - a yeast homologue of the bacterial dnaJ protein.
  findings:
    - statement: YDJ1 localizes to the cytoplasm and is concentrated in a perinuclear ring
- id: PMID:18833196
  title: Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prions.
  findings: []
- id: PMID:19536198
  title: An atlas of chaperone-protein interactions in Saccharomyces cerevisiae.
  findings: []
- id: PMID:20850366
  title: A chaperone cascade sorts proteins for posttranslational membrane insertion into the endoplasmic reticulum.
  findings: []
- id: PMID:23217712
  title: CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression.
  findings: []
- id: PMID:25344756
  title: Rsp5/Nedd4 is the main ubiquitin ligase that targets cytosolic misfolded proteins following heat stress.
  findings: []
- id: PMID:25853343
  title: Cytosolic Hsp70 and co-chaperones constitute a novel system for tRNA import into the nucleus.
  findings: []
- id: PMID:26928762
  title: One library to make them all - streamlining the creation of yeast libraries via a SWAp-Tag strategy.
  findings: []
- id: PMID:30358795
  title: The cellular economy of the Saccharomyces cerevisiae zinc proteome.
  findings: []
- id: PMID:37968396
  title: The social and structural architecture of the yeast protein interactome.
  findings: []
- id: PMID:8144572
  title: Differential regulation of Hsp70 subfamilies by the eukaryotic DnaJ homologue YDJ1.
  findings: []
- id: PMID:9632766
  title: Molecular mechanism governing heme signaling in yeast - a higher-order complex mediates heme regulation of the transcriptional activator HAP1.
  findings: []
- id: PMID:9674429
  title: Hsp104, Hsp70, and Hsp40 - a novel chaperone system that rescues previously aggregated proteins.
  findings:
    - statement: Hsp104 cooperates with Hsp70 and Hsp40 (YDJ1) to reactivate aggregated proteins
- id: PMID:9774392
  title: Protein folding activity of Hsp70 is modified differentially by the hsp40 co-chaperones Sis1 and Ydj1.
  findings:
    - statement: YDJ1 suppresses thermally induced aggregation of luciferase
    - statement: YDJ1:Ssa1 promotes up to four times more luciferase refolding than Sis1:Ssa1
    - statement: YDJ1 contains a zinc finger region absent from Sis1 that enhances chaperone function
core_functions:
- description: >-
    Hsp40/DnaJ co-chaperone that stimulates ATPase activity of Hsp70 (Ssa1) and delivers
    substrate proteins for folding. Functions in protein refolding with Hsp104/Hsp70,
    de novo protein folding, ERAD, and protein targeting to ER.
  molecular_function:
    id: GO:0001671
    label: ATPase activator activity
  directly_involved_in:
  - id: GO:0042026
    label: protein refolding
  - id: GO:0006458
    label: "'de novo' protein folding"
  - id: GO:0034605
    label: cellular response to heat
  - id: GO:0036503
    label: ERAD pathway
  - id: GO:0045047
    label: protein targeting to ER
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0048471
    label: perinuclear region of cytoplasm
- description: >-
    Protein folding chaperone activity - binds unfolded/denatured substrates via C-terminal
    peptide-binding domain and zinc finger region, delivering them to Hsp70 for folding.
    Replacement for GO:0051082 which is proposed for obsoletion.
  molecular_function:
    id: GO:0044183
    label: protein folding chaperone
  directly_involved_in:
  - id: GO:0006457
    label: protein folding
  locations:
  - id: GO:0005829
    label: cytosol