Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic (IBA) nuclear localization transferred from the broader HSP70 family. HSPA14 is documented as cytosolic and ribosome-associated; there is no experimental support for it acting in the nucleus. Reason: This family-level PANTHER transfer reflects nuclear roles of canonical HSP70s, not HSPA14. UniProt records the subcellular location as cytoplasm/cytosol only, consistent with its dedicated role as a ribosome-associated RAC subunit. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005886 plasma membrane	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic (IBA) plasma-membrane localization transferred from HSP70 family members. HSPA14 is a cytosolic ribosome-associated chaperone with no evidence of acting at the plasma membrane. Reason: Family-level transfer inconsistent with HSPA14's documented cytosolic localization; no experimental support for a plasma-membrane site of action. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0016887 ATP hydrolysis activity	IBA GO_REF:0000033	ACCEPT	Summary: HSPA14 possesses an HSP70 nucleotide-binding domain and hydrolyzes ATP; within RAC its ATPase activity is stimulated by the J-protein DNAJC2. ATP hydrolysis is central to the HSP70 chaperone cycle that HSPA14 contributes to. Reason: Consistent with the HSP70 fold and explicitly supported by UniProt, which states DNAJC2 stimulates HSPA14's ATPase activity within the RAC complex. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt In the RAC complex, binds to the nascent polypeptide chain, while DNAJC2 stimulates its ATPase activity.
GO:0031072 heat shock protein binding	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2 PMID:16002468 Purification of MPP11 revealed that it forms a stable complex with Hsp70L1, a distantly related
GO:0044183 protein folding chaperone	IBA GO_REF:0000033	ACCEPT	Summary: As the HSP70 subunit of RAC, HSPA14 acts as a chaperone that binds nascent polypeptides and assists their folding co-translationally. This is its core molecular function. Reason: Directly supported by UniProt FUNCTION (RAC binds and maintains nascent polypeptides in a folding-competent state) and by the RAC characterization in PMID:16002468. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt a complex involved in folding or maintaining nascent polypeptides in a folding-
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0042026 protein refolding	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Protein refolding is a hallmark of canonical stress-induced HSP70s. HSPA14 is specialized for co-translational ('de novo') folding of nascent chains as a RAC subunit, not for stress-induced refolding of denatured proteins. Reason: Family-level transfer of the canonical HSP70 refolding role; HSPA14's documented activity is co-translational nascent-chain folding within RAC, better captured by GO:0051083. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt a complex involved in folding or maintaining nascent polypeptides in a folding-
GO:0005840 ribosome	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: PMID:16002468 MPP11 is localized to the cytosol and associates with ribosomes
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based annotation of ATP binding via the HSP70 nucleotide-binding domain. HSPA14 contains a canonical HSP70 NBD. Reason: Consistent with the HSP70 fold and the nucleotide-dependent chaperone cycle; ATP binding underlies the ATPase activity stimulated by DNAJC2. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt SIMILARITY: Belongs to the heat shock protein 70 family.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	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. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0016887 ATP hydrolysis activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based ATP hydrolysis annotation, redundant with the IBA ATPase annotation and consistent with the HSP70 NBD. Reason: Same enzymatic activity as the IBA annotation; supported by the HSP70 fold and by DNAJC2 stimulation of HSPA14 ATPase activity. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt while DNAJC2 stimulates its ATPase activity.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	KEEP AS NON CORE	Summary: High-throughput IntAct interaction with NFAM1 (Q8NET5). Bare protein binding is uninformative, and NFAM1 is unrelated to HSPA14's chaperone function. Reason: Isolated high-throughput interaction with a non-chaperone partner (NFAM1); uninformative protein binding term that does not reflect HSPA14's RAC/co-translational folding role. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt SIMILARITY: Belongs to the heat shock protein 70 family.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MODIFY	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 Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	MODIFY	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 Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MODIFY	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 Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2
GO:0006457 protein folding	NAS PMID:16002468 The chaperones MPP11 and Hsp70L1 form the mammalian ribosome...	KEEP AS NON CORE	Summary: ComplexPortal NAS annotation of protein folding for the RAC complex. HSPA14 participates in folding nascent chains; the more specific process is co-translational folding. Reason: Protein folding is the broad outcome of the RAC chaperone module; retained as a non-core process, with the precise process captured by GO:0051083. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt a complex involved in folding or maintaining nascent polypeptides in a folding-
GO:0101031 protein folding chaperone complex	IPI PMID:16002468 The chaperones MPP11 and Hsp70L1 form the mammalian ribosome...	ACCEPT	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. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt Component of ribosome-associated complex (RAC), a heterodimer
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	KEEP AS NON CORE	Summary: High-throughput membrane-proteome detection. HSPA14 is a cytosolic, ribosome-associated chaperone; any membrane association is peripheral, not a core localization. Reason: HDA detection in a membrane proteome; peripheral to HSPA14's documented cytosolic/ribosome-associated site of action. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist...	ACCEPT	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. Supporting Evidence: file:human/HSPA14/HSPA14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005515 protein binding	IPI PMID:16002468 The chaperones MPP11 and Hsp70L1 form the mammalian ribosome...	MODIFY	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 Supporting Evidence: PMID:16002468 Purification of MPP11 revealed that it forms a stable complex with Hsp70L1, a distantly related
GO:0005829 cytosol	IDA PMID:16002468 The chaperones MPP11 and Hsp70L1 form the mammalian ribosome...	ACCEPT	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. Supporting Evidence: PMID:16002468 MPP11 is localized to the cytosol and associates with ribosomes
GO:0005840 ribosome	IDA PMID:16002468 The chaperones MPP11 and Hsp70L1 form the mammalian ribosome...	ACCEPT	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. Supporting Evidence: PMID:16002468 MPP11 is localized to the cytosol and associates with ribosomes
GO:0051083 'de novo' cotranslational protein folding	TAS PMID:16002468 The chaperones MPP11 and Hsp70L1 form the mammalian ribosome...	ACCEPT	Summary: HSPA14, as the HSP70 subunit of RAC, assists co-translational folding of nascent polypeptides at the ribosome. This is the precise core biological process for HSPA14. Reason: Directly supported by the RAC characterization (cotranslational interaction with nascent polypeptides) and UniProt FUNCTION; the most specific and accurate BP for HSPA14. Supporting Evidence: PMID:16002468 Soluble Hsp70 homologs cotranslationally interact with nascent polypeptides in file:human/HSPA14/HSPA14-uniprot.txt a complex involved in folding or maintaining nascent polypeptides in a folding-

Core Functions

Hsp70/DnaK-type chaperone subunit of the ribosome-associated complex (RAC) that binds nascent polypeptide chains at the ribosome and, with its J-protein partner DNAJC2, assists their co-translational folding in an ATP-dependent manner.

Molecular Function:

protein folding chaperone

Cellular Locations:

cytosol ribosome

Supporting Evidence:

file:human/HSPA14/HSPA14-uniprot.txt
a complex involved in folding or maintaining nascent polypeptides in a folding-
PMID:16002468
Soluble Hsp70 homologs cotranslationally interact with nascent polypeptides in

ATP binding and DNAJC2-stimulated ATP hydrolysis through the HSP70 nucleotide-binding domain, driving the RAC chaperone cycle on nascent chains.

Molecular Function:

ATP hydrolysis activity

Cellular Locations:

cytosol

Supporting Evidence:

file:human/HSPA14/HSPA14-uniprot.txt
while DNAJC2 stimulates its ATPase activity.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB Subcellular Location vocabulary mapping

PMID:16002468

The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex.

Human MPP11 (DNAJC2) forms a stable heterodimeric ribosome-associated complex (RAC) with Hsp70L1 (HSPA14), the mammalian counterpart of yeast Ssz1p/zuotin, functioning in co-translational folding at the ribosome.
HSPA14/RAC is cytosolic and associates with ribosomes, consistent with action at the ribosomal exit tunnel.

PMID:19946888

Defining the membrane proteome of NK cells.

PMID:21231916

The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

file:human/HSPA14/HSPA14-uniprot.txt

UniProt entry Q0VDF9 (HSP7E_HUMAN), Heat shock 70 kDa protein 14 / HSP70L1

HSPA14 is the Hsp70/DnaK-type subunit of the ribosome-associated complex (RAC), a heterodimer with the Hsp40/DnaJ-type co-chaperone DNAJC2; it binds nascent polypeptides while DNAJC2 stimulates its ATPase activity. It is cytosolic and belongs to the HSP70 family.

Suggested Experiments

Experiment: Reconstitute human RAC (HSPA14 + DNAJC2) in vitro and measure ATPase activity alone and in the presence of ribosomes and a ribosome-bound HSP70 to test whether HSPA14 stimulates the partner HSP70 ATPase, as in yeast.

Experiment: Selective ribosome profiling or nascent-chain crosslinking after HSPA14 knockdown to define the co-translational client repertoire and folding defects.

Experiment: Domain-swap and point-mutation analysis of the HSPA14 nucleotide-binding and substrate-binding domains to map the determinants of DNAJC2 binding and nascent-chain engagement.

📚 Additional Documentation

Notes

(HSPA14-notes.md)

HSPA14 (HSP70L1 / HSP70-like protein 1) — research notes

UniProt: Q0VDF9 (HSP7E_HUMAN), 509 aa. Gene synonyms HSP60, HSP70L1.

Core identity

HSP70-family protein and the Hsp70/DnaK-type subunit of the mammalian
ribosome-associated complex (RAC), a heterodimer with the Hsp40/DnaJ-type
co-chaperone DNAJC2 (MPP11). RAC acts at the ribosomal exit tunnel to assist
co-translational folding of nascent polypeptides.

[file:human/HSPA14/HSPA14-uniprot.txt "FUNCTION: Component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, binds to the nascent polypeptide chain, while DNAJC2 stimulates its ATPase activity."]
[file:human/HSPA14/HSPA14-uniprot.txt "SUBUNIT: Component of ribosome-associated complex (RAC), a heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2."]
[file:human/HSPA14/HSPA14-uniprot.txt "SUBCELLULAR LOCATION: Cytoplasm, cytosol"]

RAC paper (PMID:16002468, Otto et al. 2005 PNAS)

Identified the mammalian RAC as MPP11(DNAJC2)/Hsp70L1.
- PMID:16002468
- PMID:16002468
- Important nuance: like its yeast counterpart Ssz1p, Hsp70L1 is an ATYPICAL Hsp70. In yeast RAC, Ssz1p/zuotin (RAC) act to stimulate the ATPase of the ribosome-bound Hsp70 Ssb1/2p; RAC itself is the co-chaperone module. So HSPA14's own ATP-hydrolysis "chaperone" role is not a canonical autonomous foldase.
- PMID:16002468
- HeLa immunofluorescence + rat liver fractionation: cytosolic, ribosome-associated.
- PMID:16002468

GO annotation review notes (goa.tsv)

IBA nucleus / plasma membrane: family-level PANTHER transfers from canonical Hsp70s; no experimental support for HSPA14 in nucleus or PM. UniProt SUBCELLULAR LOCATION = cytoplasm/cytosol only. -> MARK_AS_OVER_ANNOTATED.
IBA ATP hydrolysis activity / IEA ATP hydrolysis: HSP70 fold present; HSPA14 has nucleotide-binding domain. ATPase is stimulated by DNAJC2 in the RAC. Keep ATP binding (KW) and ATP hydrolysis as supported by fold + UniProt FUNCTION (DNAJC2 stimulates its ATPase activity). Core enzymatic-ish MF.
IBA heat shock protein binding GO:0031072: as RAC subunit it binds DNAJC2 (an Hsp40); reasonable. ACCEPT non-core? It binds its J-protein partner. Keep as supporting.
IBA / IEA protein folding chaperone (GO:0044183 / GO:0140662): HSPA14 functions in co-translational folding as part of RAC. GO:0044183 protein folding chaperone is a reasonable core-ish MF. But it is a co-chaperone module (with DNAJC2), assisting nascent-chain folding — keep as core MF (chaperone) with caveat.
protein refolding GO:0042026 IBA: canonical Hsp70 refolding transferred from family; HSPA14 is specialized for co-translational (de novo) folding, not stress refolding. MARK_AS_OVER_ANNOTATED / KEEP_AS_NON_CORE.
ribosome (GO:0005840) colocalizes_with IBA + IDA (PMID:16002468): directly shown. ACCEPT.
cytosol GO:0005829 IBA/IEA/IDA (PMID:21231916, PMID:16002468): ACCEPT (IDA core localization).
membrane GO:0016020 HDA (PMID:19946888): high-throughput membrane-proteome detection; HSPA14 is cytosolic/ribosome-associated; peripheral. KEEP_AS_NON_CORE.
protein folding GO:0006457 NAS (ComplexPortal, PMID:16002468): RAC role. KEEP_AS_NON_CORE (downstream process of chaperone module).
protein folding chaperone complex GO:0101031 part_of IPI (PMID:16002468): the RAC complex. ACCEPT (this is exactly RAC).
'de novo' cotranslational protein folding GO:0051083 TAS (PMID:16002468): the precise BP for RAC. ACCEPT as core process.
protein binding IPI: partners DNAJC2 (Q99543) — informative (RAC partner) -> capture as Hsp70/chaperone binding; NFAM1 (Q8NET5) — HT interactome, not chaperone-related. Keep DNAJC2 ones meaningful, NFAM1 over-annotated.

Partner ID map: Q99543=DNAJC2(MPP11); Q8NET5=NFAM1.

Immunoadjuvant / DC activation

Hsp70L1 was reported to activate dendritic cells and act as a Th1 adjuvant
(PubMed:14592822, 15930317, 18851947). This is an applied/immunology property,
not a core GO molecular function; not in GOA. Noted, not annotated.

Core function synthesis

Hsp70/DnaK-type chaperone subunit of RAC — ATP-dependent, co-translational
folding of nascent chains (GO:0044183 protein folding chaperone; process
GO:0051083 de novo cotranslational protein folding; complex GO:0101031).
ATP binding / ATP hydrolysis (HSP70 NBD), stimulated by DNAJC2.

Pn Notes

(HSPA14-pn-notes.md)

HSPA14 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q0VDF9
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-07b
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/HSPA14/HSPA14-ai-review.yaml
AIGR review HTML: present - genes/human/HSPA14/HSPA14-ai-review.html
Gene notes: present - genes/human/HSPA14/HSPA14-notes.md
GOA TSV: present - genes/human/HSPA14/HSPA14-goa.tsv
UniProt record: present - genes/human/HSPA14/HSPA14-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/HSPA14.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/HSPA14.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

Description: HSPA14 (Heat shock 70 kDa protein 14, also called HSP70L1 / HSP70-like protein 1) is an atypical, divergent member of the HSP70 family and the Hsp70/DnaK-type subunit of the mammalian ribosome-associated complex (RAC). RAC is a stable cytosolic heterodimer of HSPA14 and the Hsp40/DnaJ-type co-chaperone DNAJC2 (MPP11) that docks at the ribosomal exit tunnel, where it engages emerging nascent polypeptide chains and assists their co-translational ('de novo') folding. Within RAC, HSPA14 provides the nucleotide-binding/substrate-binding HSP70 module while DNAJC2 stimulates its ATPase activity; the complex couples the chaperone cycle to ongoing translation rather than acting as an autonomous stress-induced refoldase. HSPA14 is cytosolic and ribosome-associated, and has additionally been described as an immunoadjuvant capable of activating antigen-presenting cells.
Existing/core annotation action counts: ACCEPT: 13; KEEP_AS_NON_CORE: 3; MARK_AS_OVER_ANNOTATED: 3; MODIFY: 4

PN Consistency Summary

Consistency: Notes ↔ review ↔ PN RAC row converge — HSPA14 is the atypical Hsp70/DnaK subunit of RAC (heterodimer with DNAJC2/MPP11) acting cotranslationally at the ribosomal exit tunnel; ATPase stimulated by DNAJC2 (PMID:16002468). Notes flag (per MS1) that HSPA14, like yeast Ssz1p, may not be an autonomous foldase — its nucleotide cycle largely serves to stimulate the downstream ribosome-bound HSP70. The cotranslational-folding story is fully and consistently captured.
PN story / NEW pressure: The RAC/cotranslational story is ALREADY captured: review ACCEPTs GO:0051083 'de novo' cotranslational protein folding (TAS) and GO:0101031 protein folding chaperone complex; PN's GO:0051083 is correctly flagged already_in_goa_exact. The HSP70-type GO:0140662 ATP-dependent protein folding chaperone projection is the softer of the two atypical-HSP70 cases: the review itself uses GO:0044183 protein folding chaperone (parent, ACCEPT) as a core MF and MARK_AS_OVER_ANNOTATED only the stress-refolding GO:0042026. So GO:0140662 (ATP-dependent foldase child) is debatable — defensible as RAC engages nascent chains ATP-dependently, but borderline given HSPA14's Ssz1p-like atypia (uncertain intrinsic foldase activity).
Evidence alignment: PN rows carry no reference titles; the review's central PMID:16002468 (MPP11/Hsp70L1 form mammalian RAC) underpins both the GO:0051083 and complex annotations — convergent with the PN RAC subtype projection.
Verdict: RAC/cotranslational-folding projection sound and already captured; HSP70-type GO:0140662 is borderline-defensible (atypical Ssz1p-like HSP70) but should carry the caveat. Recommended edits: [MAP] keep GO:0051083 for the RAC subtype (already covered); for the HSP70-type GO:0140662 projection, scope to co-translational folding and note HSPA14's Ssz1p-like atypia (intrinsic foldase activity uncertain) rather than asserting canonical ATP-dependent refolding.

Full Consistency Review

UniProt: Q0VDF9 (HSP70L1) · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE
PN placement: two rows — Cytonuclear proteostasis|Chaperone|HSP70 system|HSP70 (type) and Translation|Cytosolic translation|Nascent peptide husbandry|Nascent peptide chaperoning|RAC component (subtype) ; PN-node mapping: HSP70 type → mapped/ok GO:0140662 ATP-dependent protein folding chaperone (more_specific_than_existing_goa); RAC subtype + parent type → mapped/ok GO:0051083 'de novo' cotranslational protein folding (already_in_goa_exact); Translation class/branch → context_only/too_broad (GO:0002181 / GO:0006412).
Consistency: Notes ↔ review ↔ PN RAC row converge — HSPA14 is the atypical Hsp70/DnaK subunit of RAC (heterodimer with DNAJC2/MPP11) acting cotranslationally at the ribosomal exit tunnel; ATPase stimulated by DNAJC2 (PMID:16002468). Notes flag (per MS1) that HSPA14, like yeast Ssz1p, may not be an autonomous foldase — its nucleotide cycle largely serves to stimulate the downstream ribosome-bound HSP70. The cotranslational-folding story is fully and consistently captured.
PN story / NEW pressure: The RAC/cotranslational story is ALREADY captured: review ACCEPTs GO:0051083 'de novo' cotranslational protein folding (TAS) and GO:0101031 protein folding chaperone complex; PN's GO:0051083 is correctly flagged already_in_goa_exact. The HSP70-type GO:0140662 ATP-dependent protein folding chaperone projection is the softer of the two atypical-HSP70 cases: the review itself uses GO:0044183 protein folding chaperone (parent, ACCEPT) as a core MF and MARK_AS_OVER_ANNOTATED only the stress-refolding GO:0042026. So GO:0140662 (ATP-dependent foldase child) is debatable — defensible as RAC engages nascent chains ATP-dependently, but borderline given HSPA14's Ssz1p-like atypia (uncertain intrinsic foldase activity).
Mapping strategy: RAC subtype → GO:0051083 needs no change (exact, already in GOA/review). HSP70-type GO:0140662: narrower than the review's accepted GO:0044183; acceptable but flag the Ssz1p-atypia caveat — if propagated, it should be co-translational-folding-scoped, not stress-refolding. Not a clear-cut rejection like HSPA13.
Evidence alignment: PN rows carry no reference titles; the review's central PMID:16002468 (MPP11/Hsp70L1 form mammalian RAC) underpins both the GO:0051083 and complex annotations — convergent with the PN RAC subtype projection.
Verdict: RAC/cotranslational-folding projection sound and already captured; HSP70-type GO:0140662 is borderline-defensible (atypical Ssz1p-like HSP70) but should carry the caveat. Recommended edits: [MAP] keep GO:0051083 for the RAC subtype (already covered); for the HSP70-type GO:0140662 projection, scope to co-translational folding and note HSPA14's Ssz1p-like atypia (intrinsic foldase activity uncertain) rather than asserting canonical ATP-dependent refolding.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-07b
review_yaml: genes/human/HSPA14/HSPA14-ai-review.yaml
PN workbook rows: 2

PN row 1: Cytonuclear proteostasis | Chaperone | HSP70 system | HSP70

UniProt: Q0VDF9
In branches: CY, TR
PN-node mapping records (path + ancestors):
- [type] Cytonuclear proteostasis|Chaperone|HSP70 system|HSP70
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0140662 ATP-dependent protein folding chaperone]
  rationale: In the PN hierarchy, the type label HSP70 within the chaperone/HSP70-system context denotes canonical HSP70 chaperones. Propagation to the GO molecular function ATP-dependent protein folding chaperone is appropriate for curation, but the PN family label is not itself a strict GO-equivalent class.
- [group] Cytonuclear proteostasis|Chaperone|HSP70 system
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN category rather than a specific GO class. The member genes span multiple activities, complexes, or contexts, so propagation from this node would overstate the shared biology; use narrower child or gene-level curations.
- [class] Cytonuclear proteostasis|Chaperone
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN category rather than a specific GO class. The member genes span multiple activities, complexes, or contexts, so propagation from this node would overstate the shared biology; use narrower child or gene-level curations.
- [branch] Cytonuclear proteostasis
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

PN row 2: Translation | Cytosolic translation | Nascent peptide husbandry | Nascent peptide chaperoning | RAC component

UniProt: Q0VDF9
In branches: CY, TR
PN-node mapping records (path + ancestors):
- [subtype] Translation|Cytosolic translation|Nascent peptide husbandry|Nascent peptide chaperoning|RAC component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0051083 'de novo' cotranslational protein folding]
  rationale: The ribosome-associated complex is a cotranslational chaperone system for emerging nascent chains. The PN subtype is a specific component class within this mechanism, so propagation to GO 'de novo' cotranslational protein folding is justified but not exact.
- [type] Translation|Cytosolic translation|Nascent peptide husbandry|Nascent peptide chaperoning
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0051083 'de novo' cotranslational protein folding]
  rationale: This PN type denotes cotranslational chaperoning of nascent peptides. The GO de novo cotranslational protein folding term is the shared process target.
- [group] Translation|Cytosolic translation|Nascent peptide husbandry
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [class] Translation|Cytosolic translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
  rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
- [branch] Translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
  rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

Projected GO annotations (3)

GO:0140662 ATP-dependent protein folding chaperone | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Cytonuclear proteostasis|Chaperone|HSP70 system|HSP70
GO:0051083 'de novo' cotranslational protein folding | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Translation|Cytosolic translation|Nascent peptide husbandry|Nascent peptide chaperoning
GO:0051083 'de novo' cotranslational protein folding | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Translation|Cytosolic translation|Nascent peptide husbandry|Nascent peptide chaperoning|RAC component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q0VDF9
gene_symbol: HSPA14
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: HSPA14 (Heat shock 70 kDa protein 14, also called HSP70L1 / HSP70-like protein 1) is an atypical, divergent member of the HSP70 family and the Hsp70/DnaK-type subunit of the mammalian ribosome-associated complex (RAC). RAC is a stable cytosolic heterodimer of HSPA14 and the Hsp40/DnaJ-type co-chaperone DNAJC2 (MPP11) that docks at the ribosomal exit tunnel, where it engages emerging nascent polypeptide chains and assists their co-translational ('de novo') folding. Within RAC, HSPA14 provides the nucleotide-binding/substrate-binding HSP70 module while DNAJC2 stimulates its ATPase activity; the complex couples the chaperone cycle to ongoing translation rather than acting as an autonomous stress-induced refoldase. HSPA14 is cytosolic and ribosome-associated, and has additionally been described as an immunoadjuvant capable of activating antigen-presenting cells.
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) nuclear localization transferred from the broader HSP70 family. HSPA14 is documented as cytosolic and ribosome-associated; there is no experimental support for it acting in the nucleus.
    action: MARK_AS_OVER_ANNOTATED
    reason: This family-level PANTHER transfer reflects nuclear roles of canonical HSP70s, not HSPA14. UniProt records the subcellular location as cytoplasm/cytosol only, consistent with its dedicated role as a ribosome-associated RAC subunit.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) plasma-membrane localization transferred from HSP70 family members. HSPA14 is a cytosolic ribosome-associated chaperone with no evidence of acting at the plasma membrane.
    action: MARK_AS_OVER_ANNOTATED
    reason: Family-level transfer inconsistent with HSPA14's documented cytosolic localization; no experimental support for a plasma-membrane site of action.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: HSPA14 possesses an HSP70 nucleotide-binding domain and hydrolyzes ATP; within RAC its ATPase activity is stimulated by the J-protein DNAJC2. ATP hydrolysis is central to the HSP70 chaperone cycle that HSPA14 contributes to.
    action: ACCEPT
    reason: Consistent with the HSP70 fold and explicitly supported by UniProt, which states DNAJC2 stimulates HSPA14's ATPase activity within the RAC complex.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: In the RAC complex, binds to the nascent polypeptide chain, while DNAJC2 stimulates its ATPase activity.
- term:
    id: GO:0031072
    label: heat shock protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: The HSPA14-DNAJC2 interaction is experimentally established (RAC heterodimer); binding its J-protein partner is part of HSPA14's co-chaperone module function.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2
    - reference_id: PMID:16002468
      supporting_text: Purification of MPP11 revealed that it forms a stable complex with Hsp70L1, a distantly related
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: As the HSP70 subunit of RAC, HSPA14 acts as a chaperone that binds nascent polypeptides and assists their folding co-translationally. This is its core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION (RAC binds and maintains nascent polypeptides in a folding-competent state) and by the RAC characterization in PMID:16002468.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: a complex involved in folding or maintaining nascent polypeptides in a folding-
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic cytosolic localization, corroborated by direct experimental evidence (IDA) and UniProt. HSPA14 acts in the cytosol as part of RAC.
    action: ACCEPT
    reason: Agrees with UniProt subcellular location and IDA evidence (PMID:16002468, PMID:21231916); cytosol is the genuine compartment of HSPA14 action.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Protein refolding is a hallmark of canonical stress-induced HSP70s. HSPA14 is specialized for co-translational ('de novo') folding of nascent chains as a RAC subunit, not for stress-induced refolding of denatured proteins.
    action: MARK_AS_OVER_ANNOTATED
    reason: Family-level transfer of the canonical HSP70 refolding role; HSPA14's documented activity is co-translational nascent-chain folding within RAC, better captured by GO:0051083.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: a complex involved in folding or maintaining nascent polypeptides in a folding-
- term:
    id: GO:0005840
    label: ribosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: colocalizes_with
  review:
    summary: HSPA14/RAC associates with ribosomes at the exit tunnel; ribosome colocalization is directly demonstrated and phylogenetically inferred.
    action: ACCEPT
    reason: Corroborated by IDA evidence in PMID:16002468 (RAC associates with ribosomes); central to its co-translational function.
    supported_by:
    - reference_id: PMID:16002468
      supporting_text: MPP11 is localized to the cytosol and associates with ribosomes
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based annotation of ATP binding via the HSP70 nucleotide-binding domain. HSPA14 contains a canonical HSP70 NBD.
    action: ACCEPT
    reason: Consistent with the HSP70 fold and the nucleotide-dependent chaperone cycle; ATP binding underlies the ATPase activity stimulated by DNAJC2.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: 'SIMILARITY: Belongs to the heat shock protein 70 family.'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated (UniProt SubCell) cytosolic localization, redundant with and consistent with the experimentally supported cytosol annotations.
    action: ACCEPT
    reason: Agrees with stronger IDA/IBA evidence and UniProt subcellular location for the same compartment.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based ATP hydrolysis annotation, redundant with the IBA ATPase annotation and consistent with the HSP70 NBD.
    action: ACCEPT
    reason: Same enzymatic activity as the IBA annotation; supported by the HSP70 fold and by DNAJC2 stimulation of HSPA14 ATPase activity.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: while DNAJC2 stimulates its ATPase activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: High-throughput IntAct interaction with NFAM1 (Q8NET5). Bare protein binding is uninformative, and NFAM1 is unrelated to HSPA14's chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Isolated high-throughput interaction with a non-chaperone partner (NFAM1); uninformative protein binding term that does not reflect HSPA14's RAC/co-translational folding role.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: 'SIMILARITY: Belongs to the heat shock protein 70 family.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0031072
      label: heat shock protein binding
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    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.
    action: MODIFY
    reason: The WITH partner is DNAJC2 (Q99543), HSPA14's RAC partner; the interaction is more precisely captured as heat shock protein binding.
    proposed_replacement_terms:
    - id: GO:0031072
      label: heat shock protein binding
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-maps interactome capturing an HSPA14-DNAJC2 (Q99543) interaction. Bare protein binding is uninformative; the partner is the RAC J-protein.
    action: MODIFY
    reason: The WITH partner DNAJC2 (Q99543) is HSPA14's RAC partner; more precisely captured as heat shock protein binding.
    proposed_replacement_terms:
    - id: GO:0031072
      label: heat shock protein binding
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: NAS
  original_reference_id: PMID:16002468
  qualifier: involved_in
  review:
    summary: ComplexPortal NAS annotation of protein folding for the RAC complex. HSPA14 participates in folding nascent chains; the more specific process is co-translational folding.
    action: KEEP_AS_NON_CORE
    reason: Protein folding is the broad outcome of the RAC chaperone module; retained as a non-core process, with the precise process captured by GO:0051083.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: a complex involved in folding or maintaining nascent polypeptides in a folding-
- term:
    id: GO:0101031
    label: protein folding chaperone complex
  evidence_type: IPI
  original_reference_id: PMID:16002468
  qualifier: part_of
  review:
    summary: HSPA14 is part of the ribosome-associated complex (RAC), a folding chaperone complex with DNAJC2. This is a precise and accurate complex annotation.
    action: ACCEPT
    reason: Directly supported by the RAC heterodimer characterization in PMID:16002468 and UniProt SUBUNIT; RAC is exactly a protein folding chaperone complex.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: Component of ribosome-associated complex (RAC), a heterodimer
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput membrane-proteome detection. HSPA14 is a cytosolic, ribosome-associated chaperone; any membrane association is peripheral, not a core localization.
    action: KEEP_AS_NON_CORE
    reason: HDA detection in a membrane proteome; peripheral to HSPA14's documented cytosolic/ribosome-associated site of action.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:21231916
  qualifier: located_in
  review:
    summary: Direct experimental evidence for cytosolic localization, consistent with HSPA14's role as a cytosolic ribosome-associated chaperone.
    action: ACCEPT
    reason: IDA-supported cytosol annotation agreeing with UniProt and other cytosol evidence; the genuine compartment of HSPA14.
    supported_by:
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16002468
  qualifier: enables
  review:
    summary: IPI interaction with DNAJC2 (Q99543) from the original RAC characterization. Bare protein binding is uninformative, but this is HSPA14's defining RAC partner.
    action: MODIFY
    reason: The WITH partner DNAJC2 (Q99543) is the J-protein partner forming RAC with HSPA14; more precisely captured as heat shock protein binding.
    proposed_replacement_terms:
    - id: GO:0031072
      label: heat shock protein binding
    supported_by:
    - reference_id: PMID:16002468
      supporting_text: Purification of MPP11 revealed that it forms a stable complex with Hsp70L1, a distantly related
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:16002468
  qualifier: located_in
  review:
    summary: Direct experimental cytosolic localization from the RAC characterization paper, consistent with all other cytosol evidence.
    action: ACCEPT
    reason: IDA cytosol annotation from PMID:16002468 (MPP11/HSPA14 localized to the cytosol); the genuine compartment of HSPA14.
    supported_by:
    - reference_id: PMID:16002468
      supporting_text: MPP11 is localized to the cytosol and associates with ribosomes
- term:
    id: GO:0005840
    label: ribosome
  evidence_type: IDA
  original_reference_id: PMID:16002468
  qualifier: colocalizes_with
  review:
    summary: Direct experimental evidence that HSPA14/RAC associates with ribosomes and comigrates with polysomes. Central to its co-translational role.
    action: ACCEPT
    reason: IDA-supported ribosome colocalization from the RAC characterization; HSPA14 acts at the ribosomal exit tunnel.
    supported_by:
    - reference_id: PMID:16002468
      supporting_text: MPP11 is localized to the cytosol and associates with ribosomes
- term:
    id: GO:0051083
    label: '''de novo'' cotranslational protein folding'
  evidence_type: TAS
  original_reference_id: PMID:16002468
  qualifier: involved_in
  review:
    summary: HSPA14, as the HSP70 subunit of RAC, assists co-translational folding of nascent polypeptides at the ribosome. This is the precise core biological process for HSPA14.
    action: ACCEPT
    reason: Directly supported by the RAC characterization (cotranslational interaction with nascent polypeptides) and UniProt FUNCTION; the most specific and accurate BP for HSPA14.
    supported_by:
    - reference_id: PMID:16002468
      supporting_text: Soluble Hsp70 homologs cotranslationally interact with nascent polypeptides in
    - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
      supporting_text: a complex involved in folding or maintaining nascent polypeptides in a folding-
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 Subcellular Location vocabulary mapping
  findings: []
- id: PMID:16002468
  title: The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publications/PMID_16002468.md title matches exactly; richly anchored in GOA as the source for GO:0005840 (ribosome, IDA), GO:0005829 (cytosol, IDA), GO:0051083 ('de novo' cotranslational protein folding, TAS), GO:0006457 (protein folding, NAS) and GO:0101031 (protein folding chaperone complex). The defining paper establishing the HSPA14/DNAJC2 RAC; directly supports both core functions. Cited in core_functions supported_by."
  findings:
  - statement: Human MPP11 (DNAJC2) forms a stable heterodimeric ribosome-associated complex (RAC) with Hsp70L1 (HSPA14), the mammalian counterpart of yeast Ssz1p/zuotin, functioning in co-translational folding at the ribosome.
    reference_section_type: ABSTRACT
  - statement: HSPA14/RAC is cytosolic and associates with ribosomes, consistent with action at the ribosomal exit tunnel.
    reference_section_type: RESULTS
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:21231916
  title: The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: file:human/HSPA14/HSPA14-uniprot.txt
  title: UniProt entry Q0VDF9 (HSP7E_HUMAN), Heat shock 70 kDa protein 14 / HSP70L1
  findings:
  - statement: HSPA14 is the Hsp70/DnaK-type subunit of the ribosome-associated complex (RAC), a heterodimer with the Hsp40/DnaJ-type co-chaperone DNAJC2; it binds nascent polypeptides while DNAJC2 stimulates its ATPase activity. It is cytosolic and belongs to the HSP70 family.
    reference_section_type: OTHER
core_functions:
- description: Hsp70/DnaK-type chaperone subunit of the ribosome-associated complex (RAC) that binds nascent polypeptide chains at the ribosome and, with its J-protein partner DNAJC2, assists their co-translational folding in an ATP-dependent manner.
  molecular_function:
    id: GO:0044183
    label: protein folding chaperone
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005840
    label: ribosome
  supported_by:
  - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
    supporting_text: a complex involved in folding or maintaining nascent polypeptides in a folding-
  - reference_id: PMID:16002468
    supporting_text: Soluble Hsp70 homologs cotranslationally interact with nascent polypeptides in
- description: ATP binding and DNAJC2-stimulated ATP hydrolysis through the HSP70 nucleotide-binding domain, driving the RAC chaperone cycle on nascent chains.
  molecular_function:
    id: GO:0016887
    label: ATP hydrolysis activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/HSPA14/HSPA14-uniprot.txt
    supporting_text: while DNAJC2 stimulates its ATPase activity.
proposed_new_terms: []
suggested_questions:
- question: Does human HSPA14 retain measurable intrinsic ATPase activity, or is it (like yeast Ssz1p) an atypical HSP70 whose nucleotide cycle is functionally subordinate to stimulating the downstream ribosome-bound HSP70 (HSPA8/Ssb-type)?
- question: What is the nascent-chain client spectrum of human RAC, and does HSPA14/DNAJC2 show substrate selectivity among co-translationally folding proteins?
- question: Is the reported immunoadjuvant/dendritic-cell-activating activity of HSP70L1 a genuine extracellular function or an artifact of recombinant protein preparations?
suggested_experiments:
- description: Reconstitute human RAC (HSPA14 + DNAJC2) in vitro and measure ATPase activity alone and in the presence of ribosomes and a ribosome-bound HSP70 to test whether HSPA14 stimulates the partner HSP70 ATPase, as in yeast.
- description: Selective ribosome profiling or nascent-chain crosslinking after HSPA14 knockdown to define the co-translational client repertoire and folding defects.
- description: Domain-swap and point-mutation analysis of the HSPA14 nucleotide-binding and substrate-binding domains to map the determinants of DNAJC2 binding and nascent-chain engagement.

HSPA14

Gene Description