id: P10591
gene_symbol: SSA1
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: >-
  SSA1 encodes the major constitutively expressed cytoplasmic Hsp70 chaperone in S. cerevisiae
  (one of four SSA family members: SSA1-4). SSA1 is an ATP-dependent molecular chaperone that
  functions as a foldase/holdase, assisting de novo protein folding, protein refolding after
  stress, protein translocation across ER and mitochondrial membranes, clathrin coat disassembly,
  nuclear import, tRNA import into the nucleus, and ubiquitin-dependent protein degradation. SSA1
  cooperates with J-domain co-chaperones (Ydj1, Sis1) that stimulate its ATPase activity and
  target it to substrates, and with nucleotide exchange factors (Sse1/Sse2, Fes1) that promote
  ADP release. In collaboration with Hsp104 and Hsp40, SSA1 participates in the disaggregation
  and reactivation of aggregated proteins. SSA1 is highly abundant (approximately 269,000
  molecules/cell) and is present in the cytoplasm, cytosol, nucleus, plasma membrane, cell wall,
  and vacuole membrane. It is a pleiotropic chaperone involved in numerous protein quality
  control pathways.
existing_annotations:
# ============================================================
# IBA ANNOTATIONS (phylogenetically inferred)
# ============================================================
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SSA1 has been detected in the nucleus by multiple methods. It is involved in protein
      import into the nucleus (PMID:10347213) and in tRNA import (PMID:25853343). IBA
      annotation is consistent with IDA evidence from PMID:10347213 and HDA from PMID:11914276.
    action: ACCEPT
    reason: >-
      Correct and well-supported. SSA1 has direct experimental evidence for nuclear localization
      (IDA from PMID:10347213, HDA from PMID:11914276) and plays roles in nuclear protein import.
      The IBA is consistent with the experimental data.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SSA1 is the major cytoplasmic Hsp70 chaperone. IBA is consistent with extensive
      experimental evidence (IDA from PMID:8755907, HDA from PMID:11914276).
    action: ACCEPT
    reason: >-
      Core localization. SSA1 is constitutively expressed and highly abundant in the cytoplasm.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SSA1 has been detected at the plasma membrane by HDA (PMID:16622836). IBA is consistent.
    action: ACCEPT
    reason: >-
      Supported by proteomics data. SSA1 is known to associate with the plasma membrane.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SSA1 has well-characterized ATPase activity, demonstrated directly by IDA in PMID:7737974
      and PMID:18706386. The ATPase cycle is central to its chaperone mechanism. IBA is consistent.
    action: ACCEPT
    reason: >-
      Core molecular function. The ATPase activity of SSA1 is well established and drives
      the chaperone cycle.
    supported_by:
      - reference_id: PMID:7737974
        supporting_text: "The dissociation of ATP from hsp70 of Saccharomyces cerevisiae is stimulated by both Ydj1p and peptide substrates."
      - reference_id: PMID:18706386
        supporting_text: "Ssa1(L483W) ATPase activity was elevated 10-fold and was least stimulated by substrates or Hsp40 co-chaperones."
- term:
    id: GO:0031072
    label: heat shock protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SSA1 interacts with numerous heat shock proteins including Hsp90 (HSP82, HSC82),
      Hsp110 (SSE1, SSE2), and Hsp40s (Ydj1, Sis1). These interactions are well documented
      by co-purification and two-hybrid studies.
    action: ACCEPT
    reason: >-
      Well-supported by extensive IPI evidence. SSA1 physically interacts with HSP82 (5 experiments),
      HSC82 (3 experiments), SSE1 (10 experiments), SSE2 (3 experiments), Ydj1, Sis1, etc.
      These are functionally important chaperone-cochaperone interactions.
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SSA1 is a bona fide protein folding chaperone. It assists de novo folding of newly
      translated proteins (PMID:9789005) and refolding of denatured proteins (PMID:8947547,
      PMID:18706386). The IBA annotation correctly captures the core molecular function.
    action: ACCEPT
    reason: >-
      Core molecular function. SSA1 is the paradigmatic yeast cytoplasmic Hsp70 protein
      folding chaperone. This IBA is correct, though the more specific term GO:0140662
      (ATP-dependent protein folding chaperone) would also be appropriate.
    supported_by:
      - reference_id: PMID:9789005
        supporting_text: "yeast cytosolic OTC is assisted to its native state by the SSA class of yeast cytosolic Hsp70 proteins"
      - reference_id: PMID:8947547
        supporting_text: "These results demonstrate, for the first time, the refolding activity of Ssa1/2p in the context of the yeast cytosol, and define refolding activity as a chaperone function specific to Ssa1/2p"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SSA1 is primarily a cytosolic protein. IBA is consistent with HDA evidence (PMID:26928762).
    action: ACCEPT
    reason: >-
      Core localization. SSA1 is the major cytosolic Hsp70.
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SSA1 is directly involved in protein refolding, both alone and in collaboration with
      Hsp104 and Hsp40. IBA is consistent with IDA evidence from PMID:18706386, PMID:9674429,
      and PMID:8947547.
    action: ACCEPT
    reason: >-
      Well-supported core function. Refolding of denatured proteins is a central activity
      of SSA1.
    supported_by:
      - reference_id: PMID:9674429
        supporting_text: "in concert with Hsp40 and Hsp70, Hsp104 can reactivate proteins that have been denatured and allowed to aggregate"
      - reference_id: PMID:8947547
        supporting_text: "Depletion of Ssa1/2p had no effect on the ability of the yeast lysate to synthesize enzymatically active luciferase, but had a dramatic effect on the ability of the lysate to refold chemically denatured luciferase."
# ============================================================
# IEA ANNOTATIONS (computationally inferred)
# ============================================================
- term:
    id: GO:0000049
    label: tRNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      IEA annotation for tRNA binding. Consistent with IDA evidence from PMID:25853343 which
      demonstrates that SSA1 binds tRNA as part of a tRNA nuclear import system.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but non-core. The IEA is supported by direct experimental evidence (IDA from
      PMID:25853343) showing SSA1 binds tRNA to facilitate its nuclear import. However, tRNA
      binding is a specialized/moonlighting activity, not part of SSA1's core chaperone function.
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      SSA1 binds ATP and ADP as part of its chaperone cycle. This is a parent term of ATP
      binding and is correct but overly general.
    action: ACCEPT
    reason: >-
      Correct but general. Since more specific terms (ATP binding, ATP hydrolysis activity)
      are also annotated, this broader IEA is acceptable as a redundant parent annotation.
- term:
    id: GO:0000329
    label: fungal-type vacuole membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      SSA1 localization to the vacuole membrane is supported by IDA evidence from PMID:10745074,
      which showed SSA1 involvement in aminopeptidase I transport to the vacuole.
    action: ACCEPT
    reason: >-
      Correct. Consistent with direct experimental evidence (IDA from PMID:10745074).
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      SSA1 is an ATPase and binds ATP through its nucleotide-binding domain (NBD). This is
      core to its function.
    action: ACCEPT
    reason: >-
      Correct and fundamental. ATP binding is essential for the SSA1 chaperone cycle.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      Duplicate of the IBA and IDA annotations for cytoplasm. Correct.
    action: ACCEPT
    reason: >-
      Correct. Redundant with IBA and IDA annotations but acceptable.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      SSA1 is directly involved in protein folding as demonstrated experimentally (IDA
      from PMID:8947547). IEA is consistent.
    action: ACCEPT
    reason: >-
      Correct. Consistent with direct experimental evidence.
- term:
    id: GO:0006616
    label: SRP-dependent cotranslational protein targeting to membrane, translocation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      SSA1 has been implicated in protein translocation to the ER membrane (IDA from
      PMID:8754838). However, PMID:8947547 found that depletion of Ssa1/2p had no effect
      on translocation efficiency in vitro. The role may be more indirect.
    action: KEEP_AS_NON_CORE
    reason: >-
      Consistent with the existing IDA annotation from PMID:8754838, but this is not a core
      function of SSA1. The direct role in SRP-dependent translocation is debated, with
      PMID:8947547 showing depletion had no effect on translocation efficiency in vitro.
- term:
    id: GO:0009277
    label: fungal-type cell wall
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      SSA1 has been detected in the cell wall by IDA (PMID:8755907). IEA is consistent.
    action: ACCEPT
    reason: >-
      Correct. Consistent with direct experimental evidence.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      Duplicate of IBA and IDA annotations. Correct InterPro-based annotation.
    action: ACCEPT
    reason: >-
      Correct. Redundant with IBA and IDA annotations but acceptable.
- term:
    id: GO:0033554
    label: cellular response to stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      SSA1 is a heat shock protein involved in stress response. The more specific term
      GO:0034605 (cellular response to heat) is annotated with IDA evidence (PMID:24291094).
      This broader term is acceptable.
    action: ACCEPT
    reason: >-
      Correct but general. SSA1 is induced by and responds to various stresses. The broader
      term is acceptable alongside the more specific heat response annotation.
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      SSA1 participates in ubiquitin-dependent protein degradation as demonstrated by IMP/IGI
      evidence from PMID:27178214. IEA is consistent.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but non-core. SSA1 assists in presenting misfolded substrates to the
      ubiquitin-proteasome system, which is part of its broader protein quality control role
      but not its primary chaperone function.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      GO:0051082 (unfolded protein binding) is being considered for obsoletion. SSA1 does
      bind unfolded proteins, but this is part of its chaperone activity, not a standalone
      binding function. The appropriate replacement is GO:0044183 (protein folding chaperone)
      or more specifically GO:0140662 (ATP-dependent protein folding chaperone).
    action: MODIFY
    reason: >-
      GO:0051082 is targeted for obsoletion. SSA1 binds unfolded proteins as part of its
      ATP-dependent chaperone cycle, not as a passive binding activity. The correct annotation
      is the already-present GO:0044183 (protein folding chaperone) or its child GO:0140662
      (ATP-dependent protein folding chaperone). Since GO:0044183 is already annotated via
      IBA, this IEA annotation should be replaced.
    proposed_replacement_terms:
      - id: GO:0140662
        label: ATP-dependent protein folding chaperone
- term:
    id: GO:0051170
    label: import into nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      SSA1 is involved in nuclear import. This is a parent of GO:0006606 (protein import
      into nucleus), which has IDA/IGI evidence from PMID:10347213. IEA is consistent
      but less specific.
    action: ACCEPT
    reason: >-
      Correct but general. Consistent with the more specific experimental annotation for
      protein import into nucleus.
# ============================================================
# PROTEIN BINDING IPI ANNOTATIONS (grouped by PMID)
# ============================================================
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14729968
  review:
    summary: >-
      IPI evidence for SSA1 binding to proteins identified in the ctf13-30/CTF13 haploinsufficiency
      screen including RSC complex components. SSA1 is a chaperone that binds many client proteins.
    action: MODIFY
    reason: >-
      Protein binding is uninformative for a chaperone that by definition binds many proteins.
      The functional significance is better captured by GO:0044183 (protein folding chaperone)
      which is already annotated. These represent chaperone-client or chaperone-cochaperone
      interactions.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15102838
  review:
    summary: >-
      IPI evidence for SSA1 binding HAP1 (P0CS82). SSA1 is part of the HAP1 transcriptional
      repressor complex (CPX-1882 in ComplexPortal) where it represses HAP1 activity in
      the absence of heme. This is a specific and well-characterized chaperone-client
      interaction.
    action: MODIFY
    reason: >-
      The interaction with HAP1 is functionally significant but 'protein binding' is
      uninformative. SSA1 acts as a repressive chaperone holdase for HAP1. This is better
      captured by the chaperone annotation and the associated BP annotations
      (negative regulation of transcription, response to oxygen levels).
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15766533
  review:
    summary: >-
      IPI evidence for SSA1 binding HSP82 and HSC82 from a chaperone network mapping study.
      These are well-known Hsp70-Hsp90 interactions.
    action: MODIFY
    reason: >-
      Protein binding is uninformative. The Hsp70-Hsp90 interaction is better captured
      by GO:0031072 (heat shock protein binding) which is already annotated via IBA.
    proposed_replacement_terms:
      - id: GO:0031072
        label: heat shock protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16284124
  review:
    summary: >-
      IPI evidence for SSA1 binding RPT6 (proteasome subunit) from a proteasome interactome study.
    action: MODIFY
    reason: >-
      Protein binding is uninformative. The SSA1-proteasome interaction relates to its
      role in ubiquitin-dependent protein degradation, already captured by GO:0043161.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16429126
  review:
    summary: >-
      Large-scale proteome survey (Gavin et al. 2006) identifying many SSA1 interaction
      partners by TAP-MS. This is a high-throughput study with many interactors.
    action: MODIFY
    reason: >-
      Protein binding is uninformative for a chaperone. The interactions represent
      chaperone-client and chaperone-cochaperone relationships already captured by
      more specific annotations.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16688211
  review:
    summary: >-
      IPI evidence for SSA1 binding SSE1 (Hsp110). This study revealed Sse1 as an Hsp70
      nucleotide exchange factor. The Ssa1-Sse1 interaction is functionally critical.
    action: MODIFY
    reason: >-
      Protein binding is uninformative. The Ssa1-Sse1 interaction is a core chaperone-cochaperone
      interaction better captured by GO:0031072 (heat shock protein binding).
    proposed_replacement_terms:
      - id: GO:0031072
        label: heat shock protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17441508
  review:
    summary: >-
      IPI evidence for SSA1 binding SGT2 via Ydj1. SGT2 is involved in the GET pathway
      for tail-anchored protein targeting.
    action: MODIFY
    reason: >-
      Protein binding is uninformative. The interaction with SGT2/Ydj1 relates to SSA1's
      chaperone function in protein targeting.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17892321
  review:
    summary: >-
      Structure-templated predictions of protein interactions. Computational predictions
      validated by IPI.
    action: MODIFY
    reason: >-
      Protein binding is uninformative for a chaperone.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18555782
  review:
    summary: >-
      IPI evidence for SSA1 binding SSE1. Structural basis for Hsp70-Hsp110 cooperation.
      The Ssa1-Sse1 complex structure was determined.
    action: MODIFY
    reason: >-
      Protein binding is uninformative. This is a core Hsp70-Hsp110 chaperone interaction
      better captured by GO:0031072.
    proposed_replacement_terms:
      - id: GO:0031072
        label: heat shock protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18719252
  review:
    summary: >-
      High-quality binary protein interaction map (Yu et al. 2008). Large-scale Y2H study.
    action: MODIFY
    reason: >-
      Protein binding is uninformative for a chaperone.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19536198
  review:
    summary: >-
      Atlas of chaperone-protein interactions (Gong et al. 2009). This systematic study mapped
      the chaperone interactome and identified many SSA1 clients and cochaperones. The large
      number of interactors reflects SSA1's role as a general chaperone.
    action: MODIFY
    reason: >-
      Protein binding is uninformative. These interactions represent chaperone-client
      relationships that are an inherent part of SSA1's chaperone function. Already
      captured by 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:21734642
  review:
    summary: >-
      Combinatorial depletion analysis of SAGA/ADA complexes identified SSA1 interactions
      with SAGA subunits (SPT7, TAF5, TAF9, TAF12, UBP8).
    action: MODIFY
    reason: >-
      Protein binding is uninformative. SSA1 may chaperone assembly of the SAGA complex.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21876155
  review:
    summary: >-
      IPI evidence for SSA1 binding TFB4 (TFIIH subunit). Study showed cochaperone Ydj1
      controls TFIIH function via SSA1.
    action: MODIFY
    reason: >-
      Protein binding is uninformative. SSA1-TFIIH interaction is a chaperone-client
      relationship.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23217712
  review:
    summary: >-
      CDK-dependent Hsp70 phosphorylation controls G1 cyclin abundance. Large-scale
      chaperone interactome study showing SSA1 interacts with many proteins including
      cell cycle regulators.
    action: MODIFY
    reason: >-
      Protein binding is uninformative for a chaperone. SSA1's interactions with cell
      cycle regulators are part of its chaperone function.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24239293
  review:
    summary: >-
      IPI evidence for SSA1 binding RRP5. Rrp5 is involved in pre-rRNA processing.
    action: MODIFY
    reason: >-
      Protein binding is uninformative.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37070168
  review:
    summary: >-
      RNA-dependent interactome study. SSA1 interacts with GLC7 in an RNA-dependent manner.
    action: MODIFY
    reason: >-
      Protein binding is uninformative for a chaperone.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37968396
  review:
    summary: >-
      Social and structural architecture of yeast protein interactome. Large-scale study.
    action: MODIFY
    reason: >-
      Protein binding is uninformative for a chaperone.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9819422
  review:
    summary: >-
      IPI evidence for SSA1 binding HSP82 and CPR7. Cns1 study showed SSA1 associates
      with the Hsp90 chaperone complex.
    action: MODIFY
    reason: >-
      Protein binding is uninformative. The Ssa1-Hsp82/Cpr7 interaction is a chaperone
      network interaction better captured by GO:0031072.
    proposed_replacement_terms:
      - id: GO:0031072
        label: heat shock protein binding
# ============================================================
# NAS ANNOTATIONS (non-traceable author statement)
# ============================================================
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:15102838
  review:
    summary: >-
      NAS annotation from ComplexPortal for SSA1 nuclear localization in context of the
      HAP1 repressor complex. Consistent with IDA evidence from PMID:10347213.
    action: ACCEPT
    reason: >-
      Correct. SSA1 is present in the nucleus where it functions as part of the HAP1
      repressor complex and in nuclear protein import.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: NAS
  original_reference_id: PMID:15102838
  review:
    summary: >-
      SSA1 is part of the HAP1 transcriptional repressor complex (ComplexPortal CPX-1882)
      where it represses HAP1-dependent transcription in the absence of heme. This is a
      well-characterized indirect regulatory role.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a genuine but secondary function of SSA1. It acts as a repressive chaperone
      holdase for HAP1, preventing transcriptional activation. This is not a core molecular
      function of SSA1 but rather a consequence of its chaperone activity on a specific
      client (HAP1).
- term:
    id: GO:0070482
    label: response to oxygen levels
  evidence_type: NAS
  original_reference_id: PMID:15102838
  review:
    summary: >-
      SSA1 is part of the HAP1 complex that responds to heme/oxygen levels. The Hsp90
      chaperone cycle regulates HAP1 activation in response to heme.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a secondary consequence of SSA1's role in the HAP1 repressor complex, not
      a core function. SSA1 participates in oxygen sensing through its chaperone role
      on HAP1 but is not itself a sensor.
- term:
    id: GO:0070482
    label: response to oxygen levels
  evidence_type: NAS
  original_reference_id: PMID:9632766
  review:
    summary: >-
      Same process annotation from a different reference. PMID:9632766 describes the
      higher-order HAP1 complex mechanism.
    action: KEEP_AS_NON_CORE
    reason: >-
      Duplicate process annotation for the same indirect role. SSA1 participates in
      oxygen/heme signaling through the HAP1 complex but this is not its core function.
# ============================================================
# IDA/IMP/IGI ANNOTATIONS (direct experimental evidence)
# ============================================================
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: IDA
  original_reference_id: PMID:24291094
  review:
    summary: >-
      SSA1 is directly involved in the cellular response to heat. PMID:24291094 showed
      SSA1 coordinates translational control and protein homeostasis during severe heat stress,
      including stress granule disassembly.
    action: ACCEPT
    reason: >-
      Well-supported core function. As a heat shock protein, SSA1 plays a central role in
      the cellular response to heat stress.
- term:
    id: GO:0072671
    label: mitochondria-associated ubiquitin-dependent protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:32118579
  review:
    summary: >-
      PMID:32118579 described a protein quality control pathway at the mitochondrial outer
      membrane (mitoRQC) requiring SSA1. SSA1 assists in degradation of proteins that fail
      to import into mitochondria.
    action: KEEP_AS_NON_CORE
    reason: >-
      Genuine but secondary function. SSA1 participates in mitochondrial protein quality
      control as part of its broader role in ubiquitin-dependent protein degradation, but
      this is not its primary function.
- term:
    id: GO:0006606
    label: protein import into nucleus
  evidence_type: IDA
  original_reference_id: PMID:10347213
  review:
    summary: >-
      PMID:10347213 demonstrated that SSA1 is involved in nuclear protein import using
      direct assay. SSA1 was shown to stimulate nuclear localization signal-directed
      nuclear transport.
    action: KEEP_AS_NON_CORE
    reason: >-
      Genuine but secondary function. SSA1 facilitates nuclear import by maintaining
      substrates in import-competent conformations, which is a consequence of its
      chaperone activity rather than a specialized nuclear import function.
- term:
    id: GO:0006606
    label: protein import into nucleus
  evidence_type: IGI
  original_reference_id: PMID:10347213
  review:
    summary: >-
      IGI evidence from the same study, with genetic interaction with SSB1 (SGD:S000004571).
    action: KEEP_AS_NON_CORE
    reason: >-
      Same function as above, supported by genetic interaction data. Secondary function.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: HDA
  original_reference_id: PMID:26928762
  review:
    summary: >-
      HDA evidence from SWAp-Tag strategy for yeast library creation. Consistent with
      SSA1 being a cytosolic protein.
    action: ACCEPT
    reason: >-
      Correct core localization. SSA1 is predominantly cytosolic.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:11914276
  review:
    summary: >-
      HDA evidence from the Huh et al. global GFP-tagged protein localization study.
      SSA1-GFP was detected in the nucleus.
    action: ACCEPT
    reason: >-
      Correct. Consistent with IDA evidence.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: HDA
  original_reference_id: PMID:11914276
  review:
    summary: >-
      HDA evidence from the global localization study. SSA1 is cytoplasmic.
    action: ACCEPT
    reason: >-
      Correct core localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: HDA
  original_reference_id: PMID:16622836
  review:
    summary: >-
      HDA evidence from plasma membrane proteome study. SSA1 was detected in the plasma
      membrane fraction.
    action: ACCEPT
    reason: >-
      Correct. SSA1 is associated with the plasma membrane, consistent with IBA.
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:27178214
  review:
    summary: >-
      PMID:27178214 demonstrated SSA1's requirement for ubiquitin-dependent degradation
      of short-lived and abnormal proteins via mutant phenotype analysis.
    action: KEEP_AS_NON_CORE
    reason: >-
      Genuine but secondary function. SSA1 assists in presenting misfolded substrates
      to the ubiquitin-proteasome system. This is part of its broader protein quality
      control role.
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IGI
  original_reference_id: PMID:27178214
  review:
    summary: >-
      IGI evidence from the same study showing genetic interaction with SSE1 (SGD:S000003947)
      in proteasomal degradation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Same function as above, supported by genetic interaction. Secondary function.
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IDA
  original_reference_id: PMID:20462952
  review:
    summary: >-
      PMID:20462952 showed SSA1 functions in a quality control pathway for degradation
      of unfolded cytosolic proteins. SSA1 delivers misfolded substrates to E3 ubiquitin
      ligases Ubr1/Ubr2 for polyubiquitination.
    action: KEEP_AS_NON_CORE
    reason: >-
      Genuine but secondary function. SSA1 participates in ubiquitin-mediated protein
      quality control by delivering substrates for ubiquitination, but this is downstream
      of its core chaperone function.
- term:
    id: GO:0000049
    label: tRNA binding
  evidence_type: IDA
  original_reference_id: PMID:25853343
  review:
    summary: >-
      PMID:25853343 demonstrated that cytosolic Hsp70 (SSA1) and co-chaperones constitute
      a novel system for tRNA import into the nucleus. SSA1 directly binds tRNA.
    action: KEEP_AS_NON_CORE
    reason: >-
      Genuine but specialized function. tRNA binding is a moonlighting activity of SSA1
      related to its role in tRNA nuclear import. It is not the core chaperone function.
- term:
    id: GO:0035617
    label: stress granule disassembly
  evidence_type: IDA
  original_reference_id: PMID:24291094
  review:
    summary: >-
      PMID:24291094 showed SSA1 promotes stress granule disassembly during recovery from
      heat stress.
    action: KEEP_AS_NON_CORE
    reason: >-
      Genuine but secondary function. Stress granule disassembly is a specific consequence
      of SSA1's chaperone/disaggregase activity during stress recovery.
- term:
    id: GO:0072318
    label: clathrin coat disassembly
  evidence_type: IDA
  original_reference_id: PMID:23913685
  review:
    summary: >-
      PMID:23913685 demonstrated SSA1 participates in ATP-dependent disassembly of clathrin
      coats, functioning analogously to mammalian Hsc70/HSPA8 with auxilin/Swa2p.
    action: KEEP_AS_NON_CORE
    reason: >-
      Genuine but specialized function. Clathrin uncoating is a well-characterized Hsp70
      function conserved from yeast to mammals, but it is a specific application of the
      general chaperone/ATPase activity rather than a core function per se.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IDA
  original_reference_id: PMID:7737974
  review:
    summary: >-
      PMID:7737974 directly demonstrated that ATP dissociation from SSA1 is stimulated
      by both Ydj1p and peptide substrates. This establishes SSA1's intrinsic ATPase activity.
    action: ACCEPT
    reason: >-
      Core molecular function with direct experimental evidence.
    supported_by:
      - reference_id: PMID:7737974
        supporting_text: "The dissociation of ATP from hsp70 of Saccharomyces cerevisiae is stimulated by both Ydj1p and peptide substrates."
- term:
    id: GO:0000329
    label: fungal-type vacuole membrane
  evidence_type: IDA
  original_reference_id: PMID:10745074
  review:
    summary: >-
      PMID:10745074 showed cytosolic Hsp70s are involved in transport of aminopeptidase I
      from cytoplasm into the vacuole, and SSA1 localizes to the vacuole membrane.
    action: ACCEPT
    reason: >-
      Correct localization supported by direct experimental evidence.
- term:
    id: GO:0002181
    label: cytoplasmic translation
  evidence_type: IMP
  original_reference_id: PMID:11279042
  review:
    summary: >-
      PMID:11279042 showed SSA1 is required for translation and interacts with Sis1 and
      Pab1 on translating ribosomes. SSA-deficient strains show reduced translation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Genuine but secondary function. SSA1 associates with translating ribosomes and
      supports translation, likely through co-translational chaperone activity, but this
      is a downstream consequence of its chaperone function.
    supported_by:
      - reference_id: PMID:11279042
        supporting_text: "The yeast hsp70 homologue Ssa is required for translation and interacts with Sis1 and Pab1 on translating ribosomes."
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:10347213
  review:
    summary: >-
      Direct demonstration of SSA1 nuclear localization from the nuclear import study.
    action: ACCEPT
    reason: >-
      Correct. Direct experimental evidence for nuclear localization.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:8755907
  review:
    summary: >-
      PMID:8755907 identified Hsp70 family members in the cell wall but also confirmed
      cytoplasmic localization of SSA1.
    action: ACCEPT
    reason: >-
      Correct core localization with direct experimental evidence.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IDA
  original_reference_id: PMID:8947547
  review:
    summary: >-
      PMID:8947547 demonstrated SSA1/SSA2 refolding activity using denatured luciferase
      as a substrate. Depletion of Ssa1/2p dramatically reduced refolding capacity of
      yeast cytosol.
    action: ACCEPT
    reason: >-
      Core biological process. Direct experimental demonstration of SSA1's role in protein
      folding.
    supported_by:
      - reference_id: PMID:8947547
        supporting_text: "Depletion of Ssa1/2p had no effect on the ability of the yeast lysate to synthesize enzymatically active luciferase, but had a dramatic effect on the ability of the lysate to refold chemically denatured luciferase."
- term:
    id: GO:0006616
    label: SRP-dependent cotranslational protein targeting to membrane, translocation
  evidence_type: IDA
  original_reference_id: PMID:8754838
  review:
    summary: >-
      PMID:8754838 showed functional interaction of cytosolic hsp70 and Ydj1p in protein
      translocation in vivo. However, PMID:8947547 later found depletion of Ssa1/2p had
      no effect on translocation efficiency in vitro. The in vivo role may be indirect.
    action: KEEP_AS_NON_CORE
    reason: >-
      The direct role in SRP-dependent translocation is debated. PMID:8947547 showed that
      depletion of Ssa1/2p did not affect co- or post-translational translocation efficiency.
      The in vivo role described in PMID:8754838 may reflect SSA1's general chaperone
      function keeping precursors translocation-competent rather than a direct role in the
      SRP pathway.
    supported_by:
      - reference_id: PMID:8947547
        supporting_text: "Depletion of Ssa1/2p had no effect on the efficiency of translocation in this in vitro assay."
- term:
    id: GO:0009277
    label: fungal-type cell wall
  evidence_type: IDA
  original_reference_id: PMID:8755907
  review:
    summary: >-
      PMID:8755907 directly identified SSA1 as a cell wall protein in S. cerevisiae.
    action: ACCEPT
    reason: >-
      Correct localization. SSA1 is present in the cell wall, confirmed by UniProt
      subcellular location annotation.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IDA
  original_reference_id: PMID:18706386
  review:
    summary: >-
      PMID:18706386 characterized ATPase activity of SSA1 wild-type and mutants.
      Demonstrated effects of prion-impairing mutations on ATPase and chaperone activities.
    action: ACCEPT
    reason: >-
      Core molecular function with direct biochemical characterization.
    supported_by:
      - reference_id: PMID:18706386
        supporting_text: "Ssa1(L483W) ATPase activity was elevated 10-fold and was least stimulated by substrates or Hsp40 co-chaperones."
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IDA
  original_reference_id: PMID:18706386
  review:
    summary: >-
      PMID:18706386 measured reactivation of denatured luciferase by SSA1 wild-type
      and mutants, directly demonstrating protein refolding activity.
    action: ACCEPT
    reason: >-
      Core function. Direct biochemical demonstration of protein refolding activity.
    supported_by:
      - reference_id: PMID:18706386
        supporting_text: "Peptide binding and reactivation of denatured luciferase were enhanced in Ssa1(A17V) and Ssa1(R34K) but compromised in Ssa1(L483W)."
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IDA
  original_reference_id: PMID:9674429
  review:
    summary: >-
      PMID:9674429 (Glover & Lindquist 1998) demonstrated that Hsp104, Hsp70, and Hsp40
      form a disaggregation/refolding system. SSA1 (as the Hsp70 component) cooperates
      with Hsp104 and Ydj1 to reactivate aggregated proteins.
    action: ACCEPT
    reason: >-
      Core function. Landmark study demonstrating the Hsp104-Hsp70-Hsp40 disaggregation
      and refolding system.
    supported_by:
      - reference_id: PMID:9674429
        supporting_text: "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:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:9789005
  review:
    summary: >-
      PMID:9789005 showed that the SSA class of Hsp70 proteins assists folding of newly
      translated cytosolic enzymes in vivo. The study demonstrated SSA-dependent folding
      of ornithine transcarbamoylase (OTC). GO:0051082 is targeted for obsoletion because
      it confounds binding with chaperone activity.
    action: MODIFY
    reason: >-
      GO:0051082 (unfolded protein binding) is being obsoleted. PMID:9789005 actually
      demonstrates that SSA1 functions as a protein folding chaperone for newly translated
      proteins, not merely as an unfolded protein binder. The correct term is GO:0044183
      (protein folding chaperone) or more specifically GO:0140662 (ATP-dependent protein
      folding chaperone). SSA1 binds unfolded proteins as part of its ATP-dependent
      chaperone cycle to assist folding.
    proposed_replacement_terms:
      - id: GO:0140662
        label: ATP-dependent protein folding chaperone
    additional_reference_ids:
      - PMID:8947547
      - PMID:18706386
    supported_by:
      - reference_id: PMID:9789005
        supporting_text: "yeast cytosolic OTC is assisted to its native state by the SSA class of yeast cytosolic Hsp70 proteins"
      - reference_id: PMID:9789005
        supporting_text: "These findings indicate that, in vivo, the Hsp70 system assists in folding at least some newly translated cytosolic enzymes"
# ============================================================
# NEW ANNOTATIONS (suggested additions)
# ============================================================
- term:
    id: GO:0140662
    label: ATP-dependent protein folding chaperone
  evidence_type: IDA
  original_reference_id: PMID:9789005
  review:
    summary: >-
      SSA1 is an ATP-dependent protein folding chaperone. It uses ATP hydrolysis to drive
      cycles of substrate binding and release that assist protein folding. PMID:9789005
      demonstrated SSA-dependent folding of newly translated OTC in vivo, and PMID:8947547
      showed SSA1/2 refolding of denatured luciferase requires ATP. PMID:18706386
      characterized the ATPase cycle and its coupling to refolding. GO:0140662 is the
      most accurate MF term for SSA1, being a child of GO:0044183 (protein folding
      chaperone) and GO:0140657 (ATP-dependent activity). This term is already assigned
      by InterPro (IEA) in UniProt but is missing from the GOA file annotations.
    action: NEW
    reason: >-
      GO:0140662 (ATP-dependent protein folding chaperone) is the most specific and
      accurate molecular function term for SSA1. It replaces the obsoleting GO:0051082
      and is more specific than GO:0044183 (the IBA term). SSA1 uses ATP hydrolysis to
      drive its chaperone cycle.
    additional_reference_ids:
      - PMID:8947547
      - PMID:18706386
      - PMID:7737974
    supported_by:
      - reference_id: PMID:9789005
        supporting_text: "yeast cytosolic OTC is assisted to its native state by the SSA class of yeast cytosolic Hsp70 proteins"
      - reference_id: PMID:8947547
        supporting_text: "These results demonstrate, for the first time, the refolding activity of Ssa1/2p in the context of the yeast cytosol"
      - reference_id: PMID:18706386
        supporting_text: "Ssa1(L483W) ATPase activity was elevated 10-fold and was least stimulated by substrates or Hsp40 co-chaperones."
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, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:7737974
  title: The dissociation of ATP from hsp70 of Saccharomyces cerevisiae is stimulated
    by both Ydj1p and peptide substrates.
  findings:
    - statement: Established SSA1 intrinsic ATPase activity and stimulation by Ydj1 and peptide substrates
- id: PMID:8754838
  title: Functional interaction of cytosolic hsp70 and a DnaJ-related protein, Ydj1p,
    in protein translocation in vivo.
  findings:
    - statement: Showed SSA1/Ydj1 cooperation in protein translocation to the ER in vivo
- id: PMID:8755907
  title: Members of the Hsp70 family of proteins in the cell wall of Saccharomyces cerevisiae.
  findings:
    - statement: Identified SSA1 in the cell wall and confirmed cytoplasmic localization
- id: PMID:8947547
  title: The refolding activity of the yeast heat shock proteins Ssa1 and Ssa2 defines
    their role in protein translocation.
  findings:
    - statement: Demonstrated Ssa1/2 refolding activity with denatured luciferase
    - statement: Found Ssa1/2 depletion does not affect translocation in vitro
    - statement: Defined refolding as a Ssa1/2-specific chaperone function
- id: PMID:9632766
  title: 'Molecular mechanism governing heme signaling in yeast: a higher-order complex
    mediates heme regulation of the transcriptional activator HAP1.'
  findings:
    - statement: Described the HAP1 higher-order complex mechanism with Hsp70
- id: PMID:9674429
  title: 'Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously
    aggregated proteins.'
  findings:
    - statement: Landmark study showing Hsp104/Hsp70/Hsp40 system disaggregates and refolds aggregated proteins
    - statement: SSA1 (as Hsp70) cooperates with Hsp104 and Hsp40 in this process
- id: PMID:9789005
  title: Folding in vivo of a newly translated yeast cytosolic enzyme is mediated by
    the SSA class of cytosolic yeast Hsp70 proteins.
  findings:
    - statement: SSA class Hsp70s assist de novo folding of newly translated cytosolic enzymes
    - statement: OTC folding in vivo depends on SSA proteins
- id: PMID:9819422
  title: Cns1 is an essential protein associated with the hsp90 chaperone complex in
    Saccharomyces cerevisiae that can restore cyclophilin 40-dependent functions in cpr7Delta
    cells.
  findings:
    - statement: SSA1 associates with the Hsp90 chaperone complex via Cns1/Cpr7
- id: PMID:10347213
  title: A nuclear export signal prevents Saccharomyces cerevisiae Hsp70 Ssb1p from
    stimulating nuclear localization signal-directed nuclear transport.
  findings:
    - statement: Demonstrated SSA1 stimulates NLS-directed nuclear transport
    - statement: SSA1 localizes to the nucleus
- id: PMID:10745074
  title: Cytosolic Hsp70s are involved in the transport of aminopeptidase 1 from the
    cytoplasm into the vacuole.
  findings:
    - statement: SSA1 involved in Ape1 transport to the vacuole (Cvt pathway)
    - statement: SSA1 localizes to vacuole membrane
- id: PMID:11279042
  title: The yeast hsp70 homologue Ssa is required for translation and interacts with
    Sis1 and Pab1 on translating ribosomes.
  findings:
    - statement: SSA1 is required for translation
    - statement: Interacts with Sis1 and Pab1 on translating ribosomes
- id: PMID:11914276
  title: Subcellular localization of the yeast proteome.
  findings:
    - statement: Global GFP localization study showing SSA1 in cytoplasm and nucleus
- id: PMID:14729968
  title: The ctf13-30/CTF13 genomic haploinsufficiency modifier screen identifies the
    yeast chromatin remodeling complex RSC, which is required for the establishment of
    sister chromatid cohesion.
  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:
    - statement: SSA1 is part of the HAP1 repressor complex
    - statement: Hsp90 displaces Hsp70 to activate HAP1 in response to heme
- id: PMID:15766533
  title: 'Navigating the chaperone network: an integrative map of physical and genetic
    interactions mediated by the hsp90 chaperone.'
  findings:
    - statement: Mapped SSA1 interactions with Hsp90 chaperone network
- id: PMID:16284124
  title: 'An integrated mass spectrometry-based proteomic approach: quantitative analysis
    of tandem affinity-purified in vivo cross-linked protein complexes (QTAX) to decipher
    the 26 S proteasome-interacting network.'
  findings:
    - statement: SSA1 interacts with the 26S proteasome
- id: PMID:16429126
  title: Proteome survey reveals modularity of the yeast cell machinery.
  findings:
    - statement: Large-scale TAP-MS identifying numerous SSA1 interactors
- id: PMID:16622836
  title: The plasma membrane proteome of Saccharomyces cerevisiae and its response to
    the antifungal calcofluor.
  findings:
    - statement: SSA1 detected in the plasma membrane proteome
- id: PMID:16688211
  title: 'Chaperone network in the yeast cytosol: Hsp110 is revealed as an Hsp70 nucleotide
    exchange factor.'
  findings:
    - statement: Sse1 (Hsp110) functions as a nucleotide exchange factor for SSA1
- id: PMID:17441508
  title: SGT2 and MDY2 interact with molecular chaperone YDJ1 in Saccharomyces cerevisiae.
  findings:
    - statement: SSA1 interacts with SGT2 via Ydj1 co-chaperone
- id: PMID:17892321
  title: Structure-templated predictions of novel protein interactions from sequence information.
  findings: []
- id: PMID:18555782
  title: Structural basis for the cooperation of Hsp70 and Hsp110 chaperones in protein folding.
  findings:
    - statement: Structural characterization of SSA1-SSE1 complex
- id: PMID:18706386
  title: 'Prion-impairing mutations in Hsp70 chaperone Ssa1: effects on ATPase and chaperone
    activities.'
  findings:
    - statement: Biochemical characterization of SSA1 ATPase and refolding activities
    - statement: Mutations alter ATPase, substrate binding, and refolding differently
- id: PMID:18719252
  title: High-quality binary protein interaction map of the yeast interactome network.
  findings: []
- id: PMID:19536198
  title: 'An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications
    to protein folding pathways in the cell.'
  findings:
    - statement: Systematic mapping of SSA1 chaperone-client interactions
- id: PMID:20462952
  title: Ubr1 and Ubr2 function in a quality control pathway for degradation of unfolded
    cytosolic proteins.
  findings:
    - statement: SSA1 delivers misfolded substrates to Ubr1/Ubr2 E3 ligases for polyubiquitination
- id: PMID:21734642
  title: Combinatorial depletion analysis to assemble the network architecture of the
    SAGA and ADA chromatin remodeling complexes.
  findings: []
- id: PMID:21876155
  title: Control of the function of the transcription and repair factor TFIIH by the
    action of the cochaperone Ydj1.
  findings:
    - statement: SSA1 interacts with TFIIH subunit TFB4 via Ydj1
- id: PMID:23217712
  title: CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle
    progression.
  findings:
    - statement: SSA1 phosphorylation by CDK regulates cyclin levels
- id: PMID:23913685
  title: Clathrin coat disassembly by the yeast Hsc70/Ssa1p and auxilin/Swa2p proteins
    observed by single-particle burst analysis spectroscopy.
  findings:
    - statement: SSA1 functions with Swa2p in ATP-dependent clathrin coat disassembly
- id: PMID:24239293
  title: Rrp5 binding at multiple sites coordinates pre-rRNA processing and assembly.
  findings: []
- id: PMID:24291094
  title: Coordination of translational control and protein homeostasis during severe
    heat stress.
  findings:
    - statement: SSA1 coordinates heat stress response and stress granule disassembly
- id: PMID:25853343
  title: Cytosolic Hsp70 and co-chaperones constitute a novel system for tRNA import
    into the nucleus.
  findings:
    - statement: SSA1 binds tRNA and facilitates its import into the nucleus
- id: PMID:26928762
  title: 'One library to make them all: streamlining the creation of yeast libraries
    via a SWAp-Tag strategy.'
  findings:
    - statement: SSA1 confirmed in cytosol by SWAp-Tag proteomics
- id: PMID:27178214
  title: The requirements of yeast Hsp70 of SSA family for the ubiquitin-dependent degradation
    of short-lived and abnormal proteins.
  findings:
    - statement: SSA1 required for ubiquitin-dependent degradation of short-lived and abnormal proteins
- id: PMID:32118579
  title: A protein quality control pathway at the mitochondrial outer membrane.
  findings:
    - statement: SSA1 participates in mitochondria-associated protein quality control (mitoRQC)
- id: PMID:37070168
  title: RNA-dependent interactome allows network-based assignment of RNA-binding protein
    function.
  findings: []
- id: PMID:37968396
  title: The social and structural architecture of the yeast protein interactome.
  findings: []
core_functions:
  - molecular_function:
      id: GO:0140662
      label: ATP-dependent protein folding chaperone
    directly_involved_in:
      - id: GO:0006457
        label: protein folding
      - id: GO:0042026
        label: protein refolding
    locations:
      - id: GO:0005829
        label: cytosol
    description: >-
      SSA1 is the major cytoplasmic Hsp70 in S. cerevisiae, functioning as an ATP-dependent
      protein folding chaperone. It binds unfolded/misfolded proteins and uses ATP hydrolysis
      cycles to assist their folding, in cooperation with J-domain co-chaperones (Ydj1, Sis1)
      and nucleotide exchange factors (Sse1, Fes1). SSA1 assists both de novo protein folding
      (PMID:9789005) and refolding of denatured proteins (PMID:8947547, PMID:18706386). It also
      has intrinsic ATPase activity (GO:0016887) stimulated by co-chaperones and substrates
      (PMID:7737974). In collaboration with Hsp104 and Hsp40, it participates in disaggregation
      and refolding of aggregated proteins (PMID:9674429). As a heat shock protein, SSA1 is
      central to the cellular response to heat stress (PMID:24291094).