HSPA14

Summary: Additional nuclear capacity is a non-core lead, not the established mRAC location.

Reason: Predominant cytosolic ribosome-associated function is not exclusive, and the current tree contains the nuclear IBD on the exact target path. The focused OpenScientist report agreed that the IBA nucleus row is family carry-over and found a distinct HSPA14 chromatin lead in PMID:30635648 that needs adjudication on its own terms. Keep nucleus as non-core pending that follow-up instead of conflating the separate chromatin evidence with the phylogenetic localization row.

Summary: The plasma-membrane IBA is stale and lacks target-specific support.

Reason: The original plasma-membrane IBA cites PTN002500132, but that GO term was not recovered on the current target path. The focused OpenScientist report found only the generic membrane-fraction HDA in PMID:19946888 plus recombinant extracellular immunology leads, neither of which demonstrates endogenous plasma-membrane residence for cytosolic, ribosome-associated HSPA14.

Summary: Intrinsic HSPA14 ATP hydrolysis is over-inferred from a nucleotide-binding HSP70 fold.

Reason: Full PMID:21245388 measured purified mRAC turnover at approximately 0.01 ATP/min, above binding-defective mRAC-LKA and MPP11 but close to background; the authors explicitly withheld a definitive ATPase conclusion. ATP-binding mutants and hydrolysis-site mutants separate nucleotide binding from hydrolysis dependence because K68A/E172A complemented yeast while ATP-binding-defective LKA failed. Stimulation of a separate Hsp70 by mRAC must not be described as DNAJC2 stimulation of HSPA14 itself. The focused report adds that HSPA14 has a degenerate IDLGTTxS signature, lacks the EEVD and GGMP substrate-handling elements, and has catalytically inert fungal Ssz1 ortholog structures. These target-specific and ortholog data make intrinsic ATP hydrolysis over-inferred, while MARK_AS_OVER_ANNOTATED stays softer than removal because very slow HSPA14 turnover has not been directly excluded.

Summary: HSPA14 forms a stable heterodimer with the Hsp40/J-domain protein DNAJC2 (MPP11) within RAC, consistent with binding a heat shock/chaperone family protein.

Reason: The HSPA14-DNAJC2 interaction is experimentally established (RAC heterodimer); binding its J-protein partner is part of HSPA14's co-chaperone module function.

Summary: HSPA14 contributes to cotranslational protein folding through the mRAC chaperone complex.

Reason: The actual ancestral folding inference is consistent with target mRAC assembly and the 2011 demonstration that the complex recruits and stimulates Hsp70 on nascent chains. Direct nascent-chain binding by the HSPA14 subunit was proposed, not separately proven; its cofactor contribution to the folding machinery is supported.

Summary: Phylogenetic cytosolic localization, corroborated by direct experimental evidence (IDA) and UniProt. HSPA14 acts in the cytosol as part of RAC.

Reason: Agrees with UniProt subcellular location and IDA evidence (PMID:16002468, PMID:21231916); cytosol is the genuine compartment of HSPA14 action.

Summary: Refolding is not the established HSPA14 process; cotranslational folding is already captured.

Reason: The refolding IBD is on the actual target path and the yeast SSZ1 loss node is outside this path, but the focused report found no target-specific support for recovery of a denatured protein's activity after stress. HSPA14's supported RAC role is cotranslational nascent-chain folding, which is already captured by the GO:0051083 row from PMID:16002468, while PMID:21231916 supplies cytosol evidence without curating a refolding term for HSPA14.

Summary: HSPA14/RAC associates with ribosomes at the exit tunnel; ribosome colocalization is directly demonstrated and phylogenetically inferred.

Reason: Corroborated by IDA evidence in PMID:16002468 (RAC associates with ribosomes); central to its co-translational function.

Summary: ATP binding directly supports HSPA14 cofactor function.

Reason: Full PMID:21245388 demonstrates ATP analog cross-linking to Hsp70L1 and loss of effective complementation/cochaperone stimulation with the ATP-binding-defective LKA mutant. This is distinct from, and does not require accepting, intrinsic hydrolysis.

Summary: Automated (UniProt SubCell) cytosolic localization, redundant with and consistent with the experimentally supported cytosol annotations.

Reason: Agrees with stronger IDA/IBA evidence and UniProt subcellular location for the same compartment.

Summary: Intrinsic HSPA14 ATP hydrolysis is over-inferred from a nucleotide-binding HSP70 fold.

Reason: Full PMID:21245388 measured purified mRAC turnover at approximately 0.01 ATP/min, above binding-defective mRAC-LKA and MPP11 but close to background; the authors explicitly withheld a definitive ATPase conclusion. ATP-binding mutants and hydrolysis-site mutants separate nucleotide binding from hydrolysis dependence because K68A/E172A complemented yeast while ATP-binding-defective LKA failed. Stimulation of a separate Hsp70 by mRAC must not be described as DNAJC2 stimulation of HSPA14 itself. The focused report adds that HSPA14 has a degenerate IDLGTTxS signature, lacks the EEVD and GGMP substrate-handling elements, and has catalytically inert fungal Ssz1 ortholog structures. These target-specific and ortholog data make intrinsic ATP hydrolysis over-inferred, while MARK_AS_OVER_ANNOTATED stays softer than removal because very slow HSPA14 turnover has not been directly excluded.

Summary: Bare protein binding does not identify a useful molecular activity.

Reason: The source interaction with NFAM1 is retained as an experimental interaction observation, but the broad GO:0005515 label adds no informative molecular function. Removal is a term-specific curation choice, not a claim that the interaction is false or impossible because it is outside mRAC.

Summary: BioPlex affinity-purification interactome capturing HSPA14 interactions including DNAJC2 (Q99543, its RAC partner). The DNAJC2 interaction is biologically meaningful; bare protein binding itself is uninformative.

Reason: The biologically relevant partner here is DNAJC2 (Q99543), HSPA14's J-protein partner in RAC; this is more precisely captured as heat shock protein binding.

Proposed replacements: heat shock protein binding

Summary: IntAct interaction with DNAJC2 (Q99543), the RAC J-protein partner. Bare protein binding is uninformative but the partner is HSPA14's key chaperone partner.

Reason: The WITH partner is DNAJC2 (Q99543), HSPA14's RAC partner; the interaction is more precisely captured as heat shock protein binding.

Proposed replacements: heat shock protein binding

Summary: Multimodal cell-maps interactome capturing an HSPA14-DNAJC2 (Q99543) interaction. Bare protein binding is uninformative; the partner is the RAC J-protein.

Reason: The WITH partner DNAJC2 (Q99543) is HSPA14's RAC partner; more precisely captured as heat shock protein binding.

Proposed replacements: heat shock protein binding

Summary: Protein folding is a valid broad description of the core mRAC role.

Reason: HSPA14 contributes to the ribosome-associated chaperone complex that recruits and stimulates Hsp70 at nascent chains. The more specific cotranslational annotation does not make its protein-folding parent noncore.

Summary: HSPA14 is part of the ribosome-associated complex (RAC), a folding chaperone complex with DNAJC2. This is a precise and accurate complex annotation.

Reason: Directly supported by the RAC heterodimer characterization in PMID:16002468 and UniProt SUBUNIT; RAC is exactly a protein folding chaperone complex.

Summary: Recovered in a membrane-fraction proteome without protein-specific evidence that it associates with membranes.

Reason: UniProt: cytosol (ECO:0000269); ribosome-associated chaperone. The only membrane lead is an IBA plasma membrane row. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: KEEP_AS_NON_CORE.)

Summary: Direct experimental evidence for cytosolic localization, consistent with HSPA14's role as a cytosolic ribosome-associated chaperone.

Reason: IDA-supported cytosol annotation agreeing with UniProt and other cytosol evidence; the genuine compartment of HSPA14.

Summary: IPI interaction with DNAJC2 (Q99543) from the original RAC characterization. Bare protein binding is uninformative, but this is HSPA14's defining RAC partner.

Reason: The WITH partner DNAJC2 (Q99543) is the J-protein partner forming RAC with HSPA14; more precisely captured as heat shock protein binding.

Proposed replacements: heat shock protein binding

Summary: Direct experimental cytosolic localization from the RAC characterization paper, consistent with all other cytosol evidence.

Reason: IDA cytosol annotation from PMID:16002468 (MPP11/HSPA14 localized to the cytosol); the genuine compartment of HSPA14.

Summary: Direct experimental evidence that HSPA14/RAC associates with ribosomes and comigrates with polysomes. Central to its co-translational role.

Reason: IDA-supported ribosome colocalization from the RAC characterization; HSPA14 acts at the ribosomal exit tunnel.

Summary: HSPA14 contributes to cotranslational protein folding through the mRAC chaperone complex.

Reason: The actual ancestral folding inference is consistent with target mRAC assembly and the 2011 demonstration that the complex recruits and stimulates Hsp70 on nascent chains. Direct nascent-chain binding by the HSPA14 subunit was proposed, not separately proven; its cofactor contribution to the folding machinery is supported.