id: Q99471
gene_symbol: PFDN5
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  PFDN5 (Prefoldin subunit 5) encodes an alpha-type subunit of the heterohexameric
  prefoldin complex (also known as GimC). The prefoldin complex is a jellyfish-shaped
  molecular chaperone composed of two alpha subunits (PFDN3, PFDN5) and four beta
  subunits (PFDN1, PFDN2, PFDN4, PFDN6). Prefoldin functions as a co-chaperone/holdase
  that captures unfolded nascent polypeptides -- primarily actin and tubulin -- and
  delivers them to the group II chaperonin TRiC/CCT for ATP-dependent folding. PFDN5
  is also known as MM-1 (Myc Modulator-1) and has a well-characterized moonlighting
  function as a transcriptional corepressor of c-Myc. PFDN5/MM-1 binds the MBII region
  of the c-Myc N-terminal domain and represses c-Myc transcriptional activity through
  multiple mechanisms including recruitment of the TIF1beta/HDAC-mSin3 corepressor complex,
  promotion of c-Myc proteasomal degradation via Rabring7, and negative regulation of Wnt4
  expression via Egr-1 binding. The MM-1 isoforms show differential localization: MM-1alpha
  and MM-1gamma are nuclear and bind c-Myc, while MM-1beta is cytoplasmic and does not
  repress c-Myc transcription. Beyond cytoskeletal protein folding, the prefoldin complex
  has been shown to inhibit amyloid-beta fibrillation, suggesting roles in neuroprotection.
  PFDN5 is also implicated in RNA polymerase assembly through phylogenetic inference from yeast.
alternative_products:
- name: 1 (MM1-alpha)
  id: Q99471-1
- name: 2 (MM1-beta)
  id: Q99471-2
  sequence_note: VSP_043104
- name: 3 (MM1-gamma)
  id: Q99471-3
  sequence_note: VSP_043103
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GO:0005737 "cytoplasm" is a well-supported cellular component annotation for
      PFDN5. This IBA annotation was inferred from phylogenetic analysis (PANTHER)
      with evidence from yeast (SGD:S000001871, SGD:S000004559), Arabidopsis, and
      human PFDN5 itself. The prefoldin complex is a cytoplasmic chaperone that
      operates in the cytosol to capture unfolded nascent polypeptides and deliver
      them to the cytosolic chaperonin TRiC/CCT (PMID:9630229). Liang et al. 2020
      (PMID:32699605) describe prefoldin as "a cytoplasmic chaperone protein." The
      term "cytoplasm" is appropriately broad, as a more specific CC annotation to
      "prefoldin complex" (GO:0016272) is already present. Having both is correct:
      one describes the subcellular location and the other describes complex membership.
    action: ACCEPT
    reason: >-
      PFDN5 operates as part of the cytoplasmic prefoldin complex. The cytoplasm
      annotation is well-supported and appropriately broad, complementing the more
      specific prefoldin complex (GO:0016272) annotation. The IBA phylogenetic
      inference is sound (PMID:9630229, PMID:32699605). Consistent with PFDN1 review.
    supported_by:
    - reference_id: PMID:9630229
      supporting_text: >-
        Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers
        target proteins to it.
    - reference_id: PMID:32699605
      supporting_text: >-
        As a cytoplasmic chaperone protein, the prefoldin complex is a hybrid
        oligomer assembled from six different proteins (six subunits).
- term:
    id: GO:1990113
    label: RNA polymerase I assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GO:1990113 "RNA polymerase I assembly" is an IBA annotation inferred from
      phylogenetic analysis (PANTHER:PTN000293176) with evidence from yeast
      (SGD:S000001871). In yeast, prefoldin subunits have been shown to participate
      in the assembly of RNA polymerases I, II, and III. Tahmaz et al. 2022 describe
      that "canonical prefoldin contributes to transcription elongation" and has
      roles in nuclear gene expression control. This function is conserved across
      eukaryotes per phylogenetic inference and is consistent with the known nuclear
      localization of PFDN5 isoforms MM-1alpha and MM-1gamma (PMID:32699605). This
      represents a nuclear, non-core function distinct from the primary cytoplasmic
      chaperone role.
    action: KEEP_AS_NON_CORE
    reason: >-
      RNA polymerase I assembly is a secondary function for PFDN5, distinct from
      its core cytoplasmic co-chaperone role. The IBA phylogenetic inference from
      yeast (SGD:S000001871) is reasonable, and prefoldin subunits have documented
      nuclear roles in transcription-related processes. However, this is not the
      primary function of PFDN5 in humans.
    supported_by:
    - reference_id: PMID:32699605
      supporting_text: >-
        MM-1β and MM-1δ are mainly localized in the cytoplasm, while MM-1α and
        MM-1γ are localized in the nucleus, and MM1 isoforms that bind to c-Myc
        and TIF1β are located in the nucleus [101].
- term:
    id: GO:1990114
    label: RNA polymerase II core complex assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GO:1990114 "RNA polymerase II core complex assembly" is an IBA annotation
      inferred from phylogenetic analysis (PANTHER:PTN000293176) with evidence from
      yeast (SGD:S000001871). In yeast, prefoldin subunits contribute to RNA
      polymerase II assembly. This function is consistent with the known nuclear
      localization of PFDN5 isoforms and the broader role of prefoldin in
      transcription-related processes. However, this is a secondary function for
      PFDN5 in humans, distinct from its core cytoplasmic chaperone role.
    action: KEEP_AS_NON_CORE
    reason: >-
      RNA polymerase II assembly is a secondary function for PFDN5, supported by
      phylogenetic inference from yeast. While prefoldin subunits have documented
      roles in nuclear transcription processes, this is not the primary function
      of PFDN5 in humans, where its core role is as a cytoplasmic co-chaperone.
- term:
    id: GO:1990115
    label: RNA polymerase III assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GO:1990115 "RNA polymerase III assembly" is an IBA annotation inferred from
      phylogenetic analysis (PANTHER:PTN000293176) with evidence from yeast
      (SGD:S000001871). In yeast, prefoldin subunits contribute to RNA polymerase III
      assembly. This function is consistent with the nuclear roles of prefoldin
      subunits but represents a secondary function for PFDN5 in humans.
    action: KEEP_AS_NON_CORE
    reason: >-
      RNA polymerase III assembly is a secondary function for PFDN5, supported by
      phylogenetic inference from yeast. Not the core function of PFDN5 in humans.
- term:
    id: GO:0016272
    label: prefoldin complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GO:0016272 "prefoldin complex" is a core cellular component annotation for
      PFDN5. This IBA annotation was inferred from phylogenetic analysis (PANTHER)
      with evidence from Drosophila (FB:FBgn0038976), yeast (SGD:S000004559),
      Arabidopsis, and human PFDN5. PFDN5 is one of the two alpha subunits (PFDN3
      and PFDN5) of the heterohexameric prefoldin complex (PMID:9630229, PMID:30955883).
      The complex is registered in ComplexPortal as CPX-6149 and CPX-25767. Liang et al.
      2020 (PMID:32699605) confirm: "Eukaryotic prefoldin complex is a heterohexameric
      complex like a jellyfish-like structure, consisting of six different subunits
      (PFDN1-6): two alpha subunits (PFDN3 and PFDN5) and four beta subunits."
    action: ACCEPT
    reason: >-
      PFDN5 is a core structural alpha subunit of the prefoldin complex. The IBA
      annotation is phylogenetically well-supported and consistent with extensive
      experimental evidence from cryo-EM structural studies (PMID:30955883) and
      reconstitution experiments (PMID:23614719).
    supported_by:
    - reference_id: PMID:32699605
      supporting_text: >-
        Eukaryotic prefoldin complex is a heterohexameric complex like a jellyfish-like
        structure, consisting of six different subunits (PFDN1–6): two α subunits
        (PFDN3 and PFDN5) and four β subunits (PFDN1, PFDN2, PFDN4, and PFDN6) [8]
    - reference_id: PMID:30955883
      supporting_text: >-
        Maintaining proteostasis in eukaryotic protein folding involves cooperation of
        distinct chaperone systems.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      GO:0005634 "nucleus" inferred electronically from UniProtKB subcellular location
      vocabulary mapping. UniProt records isoform-specific localization: isoform 1
      (MM-1alpha) and isoform 3 (MM-1gamma) localize to the nucleus, while isoform 2
      (MM-1beta) is cytoplasmic. Liang et al. 2020 (PMID:32699605) confirm: "MM-1alpha
      and MM-1gamma are localized in the nucleus." The nuclear localization is consistent
      with the moonlighting function of PFDN5/MM-1 as a c-Myc transcriptional corepressor
      (PMID:9792694). This IEA annotation is correct and consistent with the TAS annotation
      from PMID:9792694.
    action: ACCEPT
    reason: >-
      Nuclear localization of PFDN5 is well-established for the MM-1alpha and MM-1gamma
      isoforms. The IEA mapping from UniProt subcellular location is correct and
      consistent with the c-Myc corepressor function (PMID:9792694, PMID:32699605).
    supported_by:
    - reference_id: PMID:32699605
      supporting_text: >-
        MM-1β and MM-1δ are mainly localized in the cytoplasm, while MM-1α and
        MM-1γ are localized in the nucleus, and MM1 isoforms that bind to c-Myc
        and TIF1β are located in the nucleus [101].
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      GO:0005737 "cytoplasm" inferred electronically from UniProtKB subcellular location
      vocabulary mapping. UniProt records that isoform 2 (MM-1beta) localizes to the
      cytoplasm. The prefoldin complex operates primarily in the cytoplasm for its
      co-chaperone function (PMID:9630229, PMID:32699605). This IEA annotation is
      consistent with the IBA annotation to the same term and is correct.
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is correct for PFDN5 -- both for the canonical prefoldin
      complex function and for the MM-1beta isoform specifically. Consistent with the
      IBA annotation and experimental evidence.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      GO:0006457 "protein folding" inferred electronically from InterPro domain mapping
      (IPR011599, the prefoldin alpha-type domain). This IEA annotation is consistent
      with the IDA and NAS annotations to the same term, and with the well-established
      role of the prefoldin complex in protein folding (PMID:9630229, PMID:30955883).
    action: ACCEPT
    reason: >-
      The IEA annotation to protein folding via InterPro is correct and consistent
      with the higher-confidence IDA and NAS annotations. The prefoldin alpha domain
      (IPR011599) is specifically associated with the protein folding function of the
      prefoldin complex (PMID:9630229, PMID:30955883).
- term:
    id: GO:0016272
    label: prefoldin complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      GO:0016272 "prefoldin complex" inferred electronically from InterPro domain mapping
      (IPR011599, the prefoldin alpha domain). PFDN5 is one of the two alpha subunits
      of the heterohexameric prefoldin complex (PMID:9630229, PMID:32699605). This IEA
      annotation is consistent with the IBA and IDA annotations to the same term.
    action: ACCEPT
    reason: >-
      PFDN5 is a core structural subunit of the prefoldin complex. The IEA mapping
      from the prefoldin alpha domain (IPR011599) to prefoldin complex membership is
      appropriate and consistent with experimental evidence (PMID:9630229, PMID:30955883).
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      GO:0032991 "protein-containing complex" was inferred electronically by the ARBA
      machine learning model (ARBA:ARBA00028902). While technically correct -- PFDN5 is
      part of the prefoldin complex, which is indeed a protein-containing complex -- this
      annotation is redundant and overly general given the more specific GO:0016272
      "prefoldin complex" annotation that is already present from IBA, IEA, and IDA
      evidence. The term "protein-containing complex" adds no informational value.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is an overly general annotation. PFDN5 is part of the prefoldin complex
      (GO:0016272), which is a child term of protein-containing complex. The more
      specific term is already annotated with IBA, IEA, and IDA evidence. The generic
      "protein-containing complex" adds no useful information. Consistent with PFDN1
      review decision.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      GO:0051082 "unfolded protein binding" is being obsoleted (go-ontology#30962). This
      IEA annotation was inferred electronically from InterPro domain mapping (IPR011599,
      the prefoldin alpha domain). While prefoldin does indeed bind unfolded proteins, the
      term "unfolded protein binding" is a pure binding term that fails to capture the
      functional significance of this interaction. Prefoldin acts as a holdase/transfer
      chaperone: it captures unfolded substrates (primarily actin and tubulin) and delivers
      them to the TRiC/CCT chaperonin for folding (PMID:9630229). The more appropriate
      term is GO:0044183 "protein folding chaperone" which captures the functional chaperone
      activity rather than just substrate binding. Consistent with PFDN1 review.
    action: MODIFY
    reason: >-
      GO:0051082 is being obsoleted. The term describes only a binding activity and does
      not capture the chaperone function of prefoldin. GO:0044183 "protein folding chaperone"
      (defined as "Binding to a protein or a protein-containing complex to assist the protein
      folding process") is the recommended replacement (PMID:9630229, PMID:30955883).
    proposed_replacement_terms:
    - id: GO:0044183
      label: protein folding chaperone
    additional_reference_ids:
    - PMID:9630229
    - PMID:30955883
    supported_by:
    - reference_id: PMID:9630229
      supporting_text: >-
        Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers
        target proteins to it.
    - reference_id: PMID:30955883
      supporting_text: >-
        PFD can act after TRiC bound its substrates to enhance the rate and yield
        of the folding reaction, suppressing non-productive reaction cycles.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17728244
  review:
    summary: >-
      GO:0005515 "protein binding" (IPI with UniProtKB:Q9DUN1/vIRF-3) from PMID:17728244,
      a study on Kaposi sarcoma-associated herpesvirus vIRF-3 stimulation of c-Myc
      transcriptional activity. The UniProt record confirms this interaction (NbExp=8).
      This is a viral-host interaction where vIRF-3 interacts with PFDN5/MM-1 to modulate
      c-Myc activity. While the interaction may be biologically relevant in the context of
      viral infection, "protein binding" is uninformative as an annotation for the host
      protein PFDN5.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative. While the PFDN5-vIRF-3 interaction is supported
      by multiple experiments and is relevant to viral manipulation of the c-Myc pathway,
      the GO term provides no functional insight. The transcriptional corepressor function
      is better captured by GO:0003714.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21516116
  review:
    summary: >-
      GO:0005515 "protein binding" (IPI with UniProtKB:Q13137/CALCOCO2) from PMID:21516116,
      a next-generation sequencing study to generate interactome datasets. This is a
      high-throughput interaction study. The biological significance of a PFDN5-CALCOCO2
      interaction is unclear. "Protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative. This high-throughput interaction screen detection
      does not provide functional insight. The core functions of PFDN5 are already captured
      by more specific annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25036637
  review:
    summary: >-
      GO:0005515 "protein binding" (IPI with UniProtKB:O14775/GNB5, UniProtKB:P62873/GNB1,
      UniProtKB:Q9NYS7/WSB2, UniProtKB:Q9UHV9/PFDN2) from PMID:25036637, a quantitative
      chaperone interaction network study. The PFDN5-PFDN2 interaction is expected since
      both are subunits of the prefoldin complex (UniProt records NbExp=8 for this interaction).
      The other interactions are from a large-scale chaperone network study. "Protein binding"
      is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative. The PFDN5-PFDN2 interaction is already captured
      by prefoldin complex membership (GO:0016272). The other interactions detected in the
      chaperone network study do not provide functional insight beyond what is captured by
      GO:0044183 and GO:0016272.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: >-
      GO:0005515 "protein binding" (IPI with UniProtKB:O76003/GLRX3, UniProtKB:P61289/PSME3,
      UniProtKB:Q13137/CALCOCO2, UniProtKB:Q9UKT9/IKZF3) from PMID:25416956, a
      proteome-scale map of the human interactome network. These are high-throughput
      interactions. The PFDN5-PSME3 interaction (NbExp=6 in UniProt) could reflect a
      connection between prefoldin and proteasome regulation, consistent with the known
      role of PFDN5/MM-1 in promoting c-Myc proteasomal degradation. However, "protein
      binding" remains uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative. While some interactions (e.g., PSME3) may relate
      to the proteasome-mediated c-Myc degradation function of PFDN5, the GO term itself
      provides no functional insight. The core functions are captured by more specific terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  review:
    summary: >-
      GO:0005515 "protein binding" (IPI with UniProtKB:P61758/VBP1, UniProtKB:Q9UHV9/PFDN2)
      from Huttlin et al. 2017 (PMID:28514442), the BioPlex human interactome study. The
      PFDN5-PFDN2 interaction (NbExp=8) and PFDN5-VBP1 interaction (NbExp=9) reflect
      prefoldin complex subunit and prefoldin-like complex interactions. VBP1 (von
      Hippel-Lindau binding protein 1) is a prefoldin-like protein. These interactions are
      already captured by GO:0016272. "Protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative. The PFDN5-PFDN2 and PFDN5-VBP1 interactions
      reflect co-membership in prefoldin/prefoldin-like complexes, already captured by
      GO:0016272. The BioPlex study does not add functional insight beyond complex membership.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  review:
    summary: >-
      GO:0005515 "protein binding" (IPI with UniProtKB:Q9UKT9/IKZF3) from PMID:31515488,
      a study on extensive disruption of protein interactions by genetic variants. The
      PFDN5-IKZF3 interaction (NbExp=7 in UniProt) has been detected in multiple studies.
      IKZF3/Aiolos is a transcription factor, and this interaction could relate to PFDN5's
      transcriptional regulatory functions. However, "protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative. While the PFDN5-IKZF3 interaction has been
      detected multiple times, the GO term provides no functional insight.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: >-
      GO:0005515 "protein binding" (IPI with numerous interactors) from Luck et al. 2020
      (PMID:32296183), a reference map of the human binary protein interactome (HuRI).
      This study detected a very large number of interactions for PFDN5, including with
      other prefoldin subunits (PFDN2, VBP1), transcription factors, and many other proteins.
      While the large number of interactions may partly reflect the coiled-coil structure
      of PFDN5, "protein binding" is uninformative as a GO annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative. This large-scale binary interactome study detected
      many interactions for PFDN5, but the GO term provides no functional insight. The core
      molecular functions of PFDN5 are already captured by GO:0044183 (protein folding
      chaperone) and GO:0003714 (transcription corepressor activity).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: >-
      GO:0005515 "protein binding" (IPI with UniProtKB:O14901/KLF11, UniProtKB:P42858/HTT,
      UniProtKB:Q7Z412/PEX26) from PMID:32814053, an interactome mapping study for
      neurodegenerative disease proteins. The PFDN5-HTT (Huntingtin) interaction is
      biologically interesting given prefoldin's role in preventing Huntingtin protein
      aggregation (PMID:32699605). However, "protein binding" remains uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative. While the PFDN5-HTT interaction may be relevant
      to prefoldin's neuroprotective role, the GO term provides no functional insight.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: >-
      GO:0005515 "protein binding" (IPI with UniProtKB:O14775/GNB5, UniProtKB:P61758/VBP1,
      UniProtKB:P62873/GNB1, UniProtKB:Q9UHV9/PFDN2) from Huttlin et al. 2021
      (PMID:33961781), a dual proteome-scale network study. These are replications of
      previously observed interactions. The PFDN5-PFDN2 and PFDN5-VBP1 interactions
      reflect prefoldin complex membership. "Protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative. These are replications of previously observed
      interactions that do not add functional insight beyond what is captured by GO:0016272
      (prefoldin complex) and GO:0044183 (protein folding chaperone).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  review:
    summary: >-
      GO:0005515 "protein binding" (IPI with UniProtKB:P62873/GNB1, UniProtKB:Q9NYS7/WSB2,
      UniProtKB:Q9UHV9/PFDN2) from multimodal cell maps study (PMID:40205054). This is
      a further replication of known interactions. "Protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative. These are further replications of known
      interactions. The relevant functions are already captured by more specific annotations
      (GO:0044183, GO:0016272).
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: >-
      GO:0005829 "cytosol" (IDA) from the Human Protein Atlas, based on curation of
      immunofluorescence data. The prefoldin complex operates in the cytosol for its
      co-chaperone function, binding nascent polypeptides and delivering them to TRiC/CCT
      (PMID:9630229). This is consistent with the IBA annotation to "cytoplasm" (GO:0005737)
      and provides a more specific localization. The cytosolic localization is expected for
      the canonical chaperone function of PFDN5 as part of the prefoldin complex.
    action: ACCEPT
    reason: >-
      Cytosol localization is well-supported by immunofluorescence data and is consistent
      with the cytoplasmic co-chaperone function of the prefoldin complex. This provides
      a more specific localization than the broader "cytoplasm" annotation.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: NAS
  original_reference_id: PMID:32699605
  review:
    summary: >-
      GO:0006457 "protein folding" (NAS) from ComplexPortal, citing Liang et al. 2020
      (PMID:32699605), a comprehensive review of prefoldin complex functions. The review
      describes how "the prefoldin complex helps protein fold correctly and prevents
      aggregation by providing class II chaperones ... with a linear, unnatural substrate
      in the cytoplasm." This NAS annotation is consistent with the IDA annotations to
      the same term and is well-supported by the review literature.
    action: ACCEPT
    reason: >-
      Protein folding is the core biological process for PFDN5 as part of the prefoldin
      complex. This NAS annotation from ComplexPortal cites a well-sourced review
      (PMID:32699605) that accurately describes the protein folding function.
    supported_by:
    - reference_id: PMID:32699605
      supporting_text: >-
        The prefoldin complex helps protein fold correctly and prevents aggregation
        by providing class II chaperones (Hsp60 molecular chaperones found in
        archaebacteria and eukaryotic cytoplasm) with a linear, unnatural substrate
        in the cytoplasm [2]
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: NAS
  original_reference_id: PMID:34761191
  review:
    summary: >-
      GO:0006457 "protein folding" (NAS) from ComplexPortal, citing Herranz-Montoya et al.
      2021 (PMID:34761191), a comprehensive analysis of prefoldins and their implication
      in cancer. The review describes prefoldins as "evolutionary conserved co-chaperones"
      that "act as co-chaperones escorting misfolded or non-native proteins to group II
      chaperonins." This NAS annotation is consistent with the IDA annotations and is
      well-supported.
    action: ACCEPT
    reason: >-
      Protein folding is the core biological process for PFDN5. This NAS annotation from
      ComplexPortal cites a comprehensive review (PMID:34761191) that accurately describes
      the co-chaperone function of prefoldin subunits.
    supported_by:
    - reference_id: PMID:34761191
      supporting_text: >-
        PFDNs are prevalently organized into hetero-hexameric complexes. Although
        they have been overlooked since their discovery and their functions remain
        elusive, several reports indicate they act as co-chaperones escorting
        misfolded or non-native proteins to group II chaperonins.
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: NAS
  original_reference_id: PMID:34761191
  review:
    summary: >-
      GO:0050821 "protein stabilization" (NAS) from ComplexPortal, citing Herranz-Montoya
      et al. 2021 (PMID:34761191). The GO definition of protein stabilization is "Any
      process involved in maintaining the structure and integrity of a protein and
      preventing it from degradation or aggregation." Prefoldin does prevent aggregation
      of unfolded substrates by capturing them and delivering them to TRiC/CCT
      (PMID:9630229). However, "protein stabilization" typically implies maintaining a
      folded protein in its native state, whereas prefoldin acts on unfolded nascent
      polypeptides as a holdase and transfer chaperone. The term is not entirely wrong
      but mischaracterizes the nature of the chaperone activity. Consistent with PFDN1
      review.
    action: KEEP_AS_NON_CORE
    reason: >-
      While prefoldin does prevent protein aggregation (which is part of the GO definition
      of protein stabilization), the primary function is not to stabilize already-folded
      proteins but rather to capture unfolded substrates and transfer them to TRiC/CCT
      for folding. The annotation is not wrong but represents a secondary aspect of
      prefoldin function. The core process (protein folding, GO:0006457) is already
      well-annotated with IDA and NAS evidence.
    supported_by:
    - reference_id: PMID:34761191
      supporting_text: >-
        PFDNs are prevalently organized into hetero-hexameric complexes. Although
        they have been overlooked since their discovery and their functions remain
        elusive, several reports indicate they act as co-chaperones escorting
        misfolded or non-native proteins to group II chaperonins.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IDA
  original_reference_id: PMID:30955883
  review:
    summary: >-
      GO:0006457 "protein folding" (IDA) from Gestaut et al. 2019 (PMID:30955883), which
      used cryo-EM, crosslinking mass spectrometry, and biochemical reconstitution to
      characterize the structural and functional interplay between the prefoldin (PFD)
      complex and TRiC/CCT chaperonin. The study demonstrates that "PFD can act after
      TRiC bound its substrates to enhance the rate and yield of the folding reaction,
      suppressing non-productive reaction cycles." This is the highest-quality direct
      experimental evidence for the protein folding function of the prefoldin complex.
    action: ACCEPT
    reason: >-
      This IDA annotation is supported by strong direct experimental evidence from Gestaut
      et al. 2019 (PMID:30955883), which demonstrated through cryo-EM and biochemical
      approaches that the PFD-TRiC supra-chaperone assembly enhances protein folding rates.
      Protein folding is the core biological process for PFDN5.
    supported_by:
    - reference_id: PMID:30955883
      supporting_text: >-
        PFD can act after TRiC bound its substrates to enhance the rate and yield
        of the folding reaction, suppressing non-productive reaction cycles.
    - reference_id: PMID:30955883
      supporting_text: >-
        The supra-chaperone assembly formed by PFD and TRiC is essential to
        prevent toxic conformations and ensure effective cellular proteostasis.
- term:
    id: GO:0016272
    label: prefoldin complex
  evidence_type: IDA
  original_reference_id: PMID:30955883
  review:
    summary: >-
      GO:0016272 "prefoldin complex" (IDA) from Gestaut et al. 2019 (PMID:30955883). This
      study used reconstituted human prefoldin complex (containing all six subunits including
      PFDN5) and characterized its structure and function through cryo-EM, crosslinking mass
      spectrometry, and biochemical assays. The cryo-EM structures (PDB: 6NR8, 6NR9, 6NRB,
      6NRC, 6NRD) include PFDN5 as chain 5. This provides direct structural evidence for
      PFDN5 membership in the prefoldin complex.
    action: ACCEPT
    reason: >-
      PFDN5 is a core structural subunit of the prefoldin complex. This IDA annotation is
      supported by high-resolution cryo-EM structural data from Gestaut et al. 2019
      (PMID:30955883) that directly demonstrates PFDN5 as a component of the human
      prefoldin complex.
    supported_by:
    - reference_id: PMID:30955883
      supporting_text: >-
        Maintaining proteostasis in eukaryotic protein folding involves cooperation of
        distinct chaperone systems. To understand how the essential ring-shaped
        chaperonin TRiC/CCT cooperates with the chaperone prefoldin/GIMc (PFD), we
        integrate cryoelectron microscopy (cryo-EM), crosslinking-mass-spectrometry
        and biochemical and cellular approaches to elucidate the structural and
        functional interplay between TRiC/CCT and PFD.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:30955883
  review:
    summary: >-
      GO:0051082 "unfolded protein binding" is being obsoleted (go-ontology#30962). This
      IDA annotation cites Gestaut et al. 2019 (PMID:30955883), which demonstrated that
      prefoldin associates with TRiC through a conserved electrostatic interface and
      undergoes conformational cycling between "latched" (open) and "engaged" (closed)
      states during substrate transfer. The paper shows that PFD functions not merely as
      a passive binder of unfolded substrates but as an active co-chaperone. GO:0044183
      "protein folding chaperone" is the appropriate replacement. Consistent with PFDN1
      review.
    action: MODIFY
    reason: >-
      GO:0051082 is being obsoleted. Gestaut et al. 2019 (PMID:30955883) demonstrates that
      prefoldin functions as a co-chaperone/holdase that cooperates with TRiC/CCT, not
      merely as an unfolded protein binder. GO:0044183 "protein folding chaperone" accurately
      describes this co-chaperone activity. The GO:0044183 definition ("Binding to a protein
      or a protein-containing complex to assist the protein folding process") appropriately
      encompasses the holdase/transfer function.
    proposed_replacement_terms:
    - id: GO:0044183
      label: protein folding chaperone
    additional_reference_ids:
    - PMID:9630229
    supported_by:
    - reference_id: PMID:30955883
      supporting_text: >-
        PFD can act after TRiC bound its substrates to enhance the rate and yield
        of the folding reaction, suppressing non-productive reaction cycles.
    - reference_id: PMID:30955883
      supporting_text: >-
        PFD alternates between an open "latched" conformation and a closed "engaged"
        conformation that aligns the PFD-TRiC substrate binding chambers.
    - reference_id: PMID:9630229
      supporting_text: >-
        Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers
        target proteins to it.
- term:
    id: GO:0001540
    label: amyloid-beta binding
  evidence_type: IDA
  original_reference_id: PMID:23614719
  review:
    summary: >-
      GO:0001540 "amyloid-beta binding" (IDA) from Sorgjerd et al. 2013 (PMID:23614719).
      This study demonstrated that recombinant human prefoldin (hPFD) inhibits
      amyloid-beta (Abeta 1-42) fibrillation in vitro and induces formation of soluble
      Abeta oligomers with reduced toxicity. The study used thioflavin T measurements
      and immunoblotting to show that hPFD directly interacts with Abeta peptides and
      modifies their aggregation pathway. While this demonstrates that the prefoldin
      complex can bind Abeta, this is not the core function of PFDN5 -- it reflects the
      general chaperone/holdase property of prefoldin applied to an amyloidogenic
      substrate. The annotation was made on the intact prefoldin complex, not PFDN5
      individually.
    action: KEEP_AS_NON_CORE
    reason: >-
      Amyloid-beta binding is a secondary, non-core function that reflects the general
      holdase/chaperone activity of the prefoldin complex applied to an amyloidogenic
      substrate. The study (PMID:23614719) used the intact hexameric complex rather than
      individual PFDN5. While the data are solid, this represents a peripheral function
      compared to the core role in actin/tubulin folding via TRiC/CCT delivery. Consistent
      with PFDN1 review.
    supported_by:
    - reference_id: PMID:23614719
      supporting_text: >-
        we investigated the effect of recombinant human PFD (hPFD) on Abeta(1-42)
        aggregation in vitro and found that hPFD inhibited Abeta fibrillation and
        induced formation of soluble Abeta oligomers.
- term:
    id: GO:0016272
    label: prefoldin complex
  evidence_type: IDA
  original_reference_id: PMID:23614719
  review:
    summary: >-
      GO:0016272 "prefoldin complex" (IDA) from Sorgjerd et al. 2013 (PMID:23614719).
      This study expressed and purified recombinant human prefoldin complex (hPFD) to
      investigate its effect on amyloid-beta aggregation. The successful reconstitution
      and purification of the hexameric complex containing PFDN5 provides direct evidence
      for PFDN5 membership in the prefoldin complex. This is consistent with the IDA
      annotation from PMID:30955883 and the IBA/IEA annotations.
    action: ACCEPT
    reason: >-
      PFDN5 is a core structural subunit of the prefoldin complex. This IDA annotation
      from PMID:23614719 provides independent experimental evidence through reconstitution
      of the human prefoldin hexamer, consistent with the structural data from PMID:30955883.
    supported_by:
    - reference_id: PMID:23614719
      supporting_text: >-
        Prefoldin (PFD) is a molecular chaperone that prevents aggregation of
        misfolded proteins.
- term:
    id: GO:1905907
    label: negative regulation of amyloid fibril formation
  evidence_type: IDA
  original_reference_id: PMID:23614719
  review:
    summary: >-
      GO:1905907 "negative regulation of amyloid fibril formation" (IDA) from Sorgjerd
      et al. 2013 (PMID:23614719). The study demonstrated that recombinant human prefoldin
      "inhibited Abeta fibrillation and induced formation of soluble Abeta oligomers" that
      were 30-40% less toxic than Abeta fibrils. Thioflavin T measurements confirmed
      reduced fibril formation. While the experimental evidence is sound, this represents
      a non-core function of the prefoldin complex -- an extension of its general
      holdase/chaperone properties to amyloidogenic substrates. The study was performed on
      the intact hexameric complex, not PFDN5 individually.
    action: KEEP_AS_NON_CORE
    reason: >-
      The experimental evidence from PMID:23614719 is solid, but this is a secondary
      function reflecting the general anti-aggregation properties of the prefoldin complex
      rather than its core role in delivering unfolded actin/tubulin to TRiC/CCT. The
      study was performed in vitro on the intact hexameric complex. Consistent with PFDN1
      review.
    supported_by:
    - reference_id: PMID:23614719
      supporting_text: >-
        we investigated the effect of recombinant human PFD (hPFD) on Abeta(1-42)
        aggregation in vitro and found that hPFD inhibited Abeta fibrillation and
        induced formation of soluble Abeta oligomers.
    - reference_id: PMID:23614719
      supporting_text: >-
        Our findings show a relation between cytotoxicity of Abeta oligomers and
        structure and suggest a possible protective role of PFD in AD.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:18281035
  review:
    summary: >-
      GO:0045892 "negative regulation of DNA-templated transcription" (IMP) from
      PMID:18281035, annotated by BHF-UCL. PFDN5/MM-1 is well-established as a
      transcriptional corepressor of c-Myc. Mori et al. 1998 (PMID:9792694) originally
      identified MM-1 as "a novel c-Myc-associating protein that represses transcriptional
      activity of c-Myc." Liang et al. 2020 (PMID:32699605) describe multiple regulatory
      mechanisms including inhibition of c-Myc E-box-dependent transcriptional activity
      via TIF1beta/HDAC-mSin3 recruitment. This is a well-supported moonlighting function
      of PFDN5 that is independent of its prefoldin complex chaperone role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Negative regulation of transcription is a well-supported moonlighting function of
      PFDN5/MM-1, independent of its core cytoplasmic co-chaperone role. The c-Myc
      corepressor function is mediated by nuclear isoforms (MM-1alpha, MM-1gamma) and
      involves recruitment of TIF1beta/HDAC-mSin3 corepressor complex (PMID:9792694,
      PMID:32699605). Classified as non-core because the primary function of PFDN5 as a
      prefoldin subunit is protein folding chaperone activity.
    supported_by:
    - reference_id: PMID:32699605
      supporting_text: >-
        (c)MM-1 inhibits the E-box-dependent transcriptional activity of c-Myc by
        recruiting a histone deacetylase (HDAC-mSin3) complex from
        TIF1β/KAP1/TRIM28 (a transcriptional co-inhibitor) (Fig
- term:
    id: GO:0090090
    label: negative regulation of canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:18281035
  review:
    summary: >-
      GO:0090090 "negative regulation of canonical Wnt signaling pathway" (IMP) from
      PMID:18281035, annotated by BHF-UCL. Liang et al. 2020 (PMID:32699605) describe
      this mechanism: MM-1 negatively regulates the expression of wnt4 by binding to
      Egr-1, thereby indirectly inhibiting c-Myc expression. This represents one of the
      multiple mechanisms by which PFDN5/MM-1 inhibits c-Myc activity. This is part of
      the moonlighting transcriptional regulatory function of PFDN5.
    action: KEEP_AS_NON_CORE
    reason: >-
      Negative regulation of Wnt signaling is part of the moonlighting transcriptional
      regulatory function of PFDN5/MM-1. It represents one of the multiple mechanisms by
      which MM-1 inhibits c-Myc activity (PMID:32699605). This is a secondary function
      compared to the core co-chaperone role.
    supported_by:
    - reference_id: PMID:32699605
      supporting_text: >-
        MM-1 negatively regulates the expression of wnt4 by binding to Egr-1,
        thereby indirectly inhibiting c-Myc expression (Fig
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: TAS
  original_reference_id: PMID:16130169
  review:
    summary: >-
      GO:0005737 "cytoplasm" (TAS) from PMID:16130169, a proteomics study of human
      umbilical vein endothelial cells. This study identified PFDN5 in the proteome of
      HUVECs, consistent with its cytoplasmic localization. The cytoplasmic localization
      is well-established for the prefoldin complex (PMID:9630229, PMID:32699605) and
      is consistent with the IBA and IEA annotations to the same term.
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is well-supported and consistent with the canonical
      co-chaperone function of the prefoldin complex. This TAS annotation is consistent
      with multiple other annotations to the same term.
- term:
    id: GO:0003714
    label: transcription corepressor activity
  evidence_type: TAS
  original_reference_id: PMID:9792694
  review:
    summary: >-
      GO:0003714 "transcription corepressor activity" (TAS) from PMID:9792694, the
      original paper by Mori et al. 1998 that identified MM-1 as "a novel c-Myc-associating
      protein that represses transcriptional activity of c-Myc." UniProt confirms: "Represses
      the transcriptional activity of MYC." Liang et al. 2020 (PMID:32699605) describe
      multiple corepressor mechanisms including recruitment of HDAC-mSin3 complex via
      TIF1beta/KAP1/TRIM28, proteasomal degradation of c-Myc via Rabring7, and
      suppression of Wnt4 via Egr-1. This is a well-characterized moonlighting function
      of PFDN5/MM-1 that is distinct from and independent of its prefoldin complex
      chaperone role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Transcription corepressor activity is a well-established moonlighting function of
      PFDN5/MM-1, distinct from the core cytoplasmic co-chaperone role. It is mediated
      specifically by the nuclear isoforms (MM-1alpha, MM-1gamma) and involves binding
      to the MBII region of c-Myc's N-terminal domain and recruitment of
      TIF1beta/HDAC-mSin3 corepressor complex (PMID:9792694, PMID:32699605). While
      this is an important biological function, the primary identity of PFDN5 is as a
      prefoldin subunit, so this is classified as non-core.
    supported_by:
    - reference_id: PMID:32699605
      supporting_text: >-
        MM-1 is one of the c-Myc NTD-terminated proteins which is bound to the MBII
        region of the NTD and can compete with TRRAP for c-Myc [99].
    - reference_id: PMID:32699605
      supporting_text: >-
        MM1, a nuclear c-Myc binding protein, inhibits c-Myc activity in the nucleus
        in various ways and is therefore considered a tumor suppressor.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: TAS
  original_reference_id: PMID:9792694
  review:
    summary: >-
      GO:0005634 "nucleus" (TAS) from PMID:9792694, the original paper by Mori et al. 1998
      that identified MM-1. The nuclear localization of PFDN5/MM-1 is well-established for
      the MM-1alpha and MM-1gamma isoforms, which bind c-Myc and function as transcriptional
      corepressors in the nucleus (PMID:32699605). Consistent with the IEA annotation to
      the same term from GO_REF:0000044.
    action: ACCEPT
    reason: >-
      Nuclear localization is well-supported for PFDN5 isoforms MM-1alpha and MM-1gamma.
      This is consistent with the moonlighting transcriptional corepressor function
      (PMID:9792694, PMID:32699605) and the IEA annotation.
    supported_by:
    - reference_id: PMID:32699605
      supporting_text: >-
        MM-1β and MM-1δ are mainly localized in the cytoplasm, while MM-1α and
        MM-1γ are localized in the nucleus, and MM1 isoforms that bind to c-Myc
        and TIF1β are located in the nucleus [101].
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: TAS
  original_reference_id: PMID:9792694
  review:
    summary: >-
      GO:0006355 "regulation of DNA-templated transcription" (TAS) from PMID:9792694.
      This is a broad parent term that encompasses the more specific GO:0045892 "negative
      regulation of DNA-templated transcription" already annotated with IMP evidence from
      PMID:18281035. PFDN5/MM-1 is well-established as a transcriptional regulator through
      its c-Myc corepressor function. However, this term is redundant with the more specific
      GO:0045892 annotation. The annotation should be modified to the more specific child
      term or kept as-is since GO:0045892 already exists.
    action: KEEP_AS_NON_CORE
    reason: >-
      Regulation of transcription is well-supported for PFDN5/MM-1 through its c-Myc
      corepressor function (PMID:9792694, PMID:32699605). While this term is broader
      than the existing GO:0045892 annotation, it is not wrong -- PFDN5 does regulate
      transcription. This is a secondary/moonlighting function. The more specific
      GO:0045892 from PMID:18281035 provides better resolution.
    supported_by:
    - reference_id: PMID:32699605
      supporting_text: >-
        MM1, a nuclear c-Myc binding protein, inhibits c-Myc activity in the nucleus
        in various ways and is therefore considered a tumor suppressor.
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GO:0044183 "protein folding chaperone" is the most appropriate molecular function
      term for PFDN5 as a prefoldin subunit. This annotation is proposed as a NEW entry
      to match the IBA annotation that exists for PFDN1 (which has this term with IBA
      evidence). Prefoldin functions as a holdase/transfer chaperone that captures unfolded
      nascent polypeptides and delivers them to TRiC/CCT for folding (PMID:9630229).
      Gestaut et al. 2019 (PMID:30955883) demonstrated that the PFD-TRiC supra-chaperone
      assembly enhances folding rates. This term is also the recommended replacement for
      the obsoleting GO:0051082 "unfolded protein binding." Note: PFDN5 does not currently
      have an explicit IBA annotation to GO:0044183 in the GOA data, unlike PFDN1 which
      does. The two MODIFY actions for GO:0051082 above recommend this term as replacement.
    action: NEW
    reason: >-
      GO:0044183 "protein folding chaperone" is the core molecular function of PFDN5 as
      a prefoldin subunit. PFDN1 already has this annotation with IBA evidence. The
      prefoldin complex is a bona fide protein folding chaperone that captures unfolded
      substrates and delivers them to TRiC/CCT (PMID:9630229, PMID:30955883). This term
      should be added to PFDN5 to replace the obsoleting GO:0051082.
    supported_by:
    - reference_id: PMID:9630229
      supporting_text: >-
        We describe the discovery of a heterohexameric chaperone protein, prefoldin,
        based on its ability to capture unfolded actin. Prefoldin binds specifically
        to cytosolic chaperonin (c-cpn) and transfers target proteins to it.
    - reference_id: PMID:30955883
      supporting_text: >-
        PFD can act after TRiC bound its substrates to enhance the rate and yield
        of the folding reaction, suppressing non-productive reaction cycles.
core_functions:
- molecular_function:
    id: GO:0044183
    label: protein folding chaperone
  description: >-
    Alpha subunit of the heterohexameric prefoldin co-chaperone complex that
    captures unfolded nascent polypeptides -- primarily actin and tubulin -- and
    delivers them to the group II chaperonin TRiC/CCT for ATP-dependent folding.
    The prefoldin complex acts as a holdase/transfer chaperone that alternates
    between open (latched) and closed (engaged) conformations during substrate
    handoff to TRiC. The PFD-TRiC supra-chaperone assembly enhances the rate
    and yield of the folding reaction and suppresses non-productive reaction
    cycles.
  supported_by:
  - reference_id: PMID:9630229
    supporting_text: >-
      We describe the discovery of a heterohexameric chaperone protein, prefoldin,
      based on its ability to capture unfolded actin. Prefoldin binds specifically
      to cytosolic chaperonin (c-cpn) and transfers target proteins to it.
  - reference_id: PMID:30955883
    supporting_text: >-
      PFD can act after TRiC bound its substrates to enhance the rate and yield
      of the folding reaction, suppressing non-productive reaction cycles.
  directly_involved_in:
  - id: GO:0006457
    label: protein folding
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0016272
    label: prefoldin complex
- molecular_function:
    id: GO:0003714
    label: transcription corepressor activity
  description: >-
    Moonlighting function as c-Myc transcriptional corepressor (MM-1). Nuclear
    isoforms (MM-1alpha and MM-1gamma) bind the MBII region of the c-Myc
    N-terminal domain and repress c-Myc transcriptional activity through
    multiple mechanisms including recruitment of the TIF1beta/HDAC-mSin3
    corepressor complex, promotion of c-Myc proteasomal degradation via Rabring7,
    and negative regulation of Wnt4 expression via Egr-1 binding. This function
    is independent of the cytoplasmic prefoldin co-chaperone role and is mediated
    by isoform-specific nuclear localization.
  supported_by:
  - reference_id: PMID:9792694
    supporting_text: >-
      MM-1 is a novel c-Myc-associating protein that represses transcriptional
      activity of c-Myc.
  - reference_id: PMID:32699605
    supporting_text: >-
      MM-1 inhibits the E-box-dependent transcriptional activity of c-Myc by
      recruiting a histone deacetylase (HDAC-mSin3) complex from
      TIF1beta/KAP1/TRIM28.
  directly_involved_in:
  - id: GO:0045892
    label: negative regulation of DNA-templated transcription
  locations:
  - id: GO:0005634
    label: nucleus
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: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:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:9630229
  title: 'Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin.'
  findings:
  - statement: >-
      Discovered the heterohexameric chaperone protein prefoldin, based on its ability
      to capture unfolded actin. Prefoldin binds specifically to cytosolic chaperonin
      (c-cpn) and transfers target proteins to it. Deletion of the gene encoding a
      prefoldin subunit in S. cerevisiae results in impaired actin and tubulin-based
      cytoskeleton functions.
    supporting_text: >-
      We describe the discovery of a heterohexameric chaperone protein, prefoldin,
      based on its ability to capture unfolded actin. Prefoldin binds specifically
      to cytosolic chaperonin (c-cpn) and transfers target proteins to it.
- id: PMID:9792694
  title: 'MM-1, a novel c-Myc-associating protein that represses transcriptional
    activity of c-Myc.'
  findings:
  - statement: >-
      Original identification of MM-1 (PFDN5) as a c-Myc-binding protein that represses
      c-Myc transcriptional activity. MM-1 binds the N-terminal domain of c-Myc.
- id: PMID:16130169
  title: Proteomics of human umbilical vein endothelial cells applied to etoposide-induced
    apoptosis.
  findings: []
- id: PMID:17728244
  title: Stimulation of c-Myc transcriptional activity by vIRF-3 of Kaposi sarcoma-associated
    herpesvirus.
  findings: []
- id: PMID:18281035
  title: Negative regulation of the Wnt signal by MM-1 through inhibiting expression
    of the wnt4 gene.
  findings:
  - statement: >-
      Demonstrates that PFDN5/MM-1 negatively regulates canonical Wnt signaling by
      cooperating with Egr-1 to repress Wnt4 transcription, thereby indirectly inhibiting
      c-Myc expression.
- id: PMID:21516116
  title: Next-generation sequencing to generate interactome datasets.
  findings: []
- id: PMID:23614719
  title: "Human prefoldin inhibits amyloid-\u03B2 (A\u03B2) fibrillation and contributes\
    \ to formation of nontoxic A\u03B2 aggregates."
  findings:
  - statement: >-
      Demonstrated that recombinant human prefoldin (hPFD) inhibits Abeta(1-42)
      fibrillation in vitro and induces formation of soluble Abeta oligomers that are
      30-40% less toxic. Shows prefoldin complex membership and amyloid-beta binding.
- id: PMID:25036637
  title: A quantitative chaperone interaction network reveals the architecture of
    cellular protein homeostasis pathways.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
- id: PMID:30955883
  title: The Chaperonin TRiC/CCT Associates with Prefoldin through a Conserved Electrostatic
    Interface Essential for Cellular Proteostasis.
  findings:
  - statement: >-
      Used cryo-EM, crosslinking mass spectrometry, and biochemical approaches to
      characterize the PFD-TRiC supra-chaperone assembly. Demonstrated that PFD enhances
      the rate and yield of TRiC-mediated protein folding, and that disrupting the
      TRiC-PFD interaction leads to accumulation of amyloid aggregates.
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the
    allele frequency spectrum in human populations.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32699605
  title: The functions and mechanisms of prefoldin complex and prefoldin-subunits.
  findings:
  - statement: >-
      Comprehensive review of prefoldin complex functions and individual subunit roles.
      Describes PFDN5/MM-1 as the most well-known prefoldin subunit with documented
      c-Myc corepressor function through multiple mechanisms: HDAC-mSin3 recruitment,
      Rabring7-mediated c-Myc degradation, and Wnt4 repression via Egr-1.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:34761191
  title: A comprehensive analysis of prefoldins and their implication in cancer.
  findings:
  - statement: >-
      Describes prefoldins as evolutionary conserved co-chaperones that act as escorts
      for misfolded or non-native proteins to group II chaperonins. Comprehensive analysis
      of prefoldin genomic alterations across cancer types.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []