DNAJC1

UniProt ID: Q96KC8
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

DNAJC1 (MTJ1/ERdj1, human homolog HTJ1) is a single-pass type I endoplasmic reticulum (and nuclear/microsomal) membrane protein of the DNAJC subfamily of J-domain co-chaperones. Its N-terminal J domain faces the ER lumen and stimulates the ATPase activity of the ER HSP70 chaperone BiP (HSPA5), while its large cytosolic C-terminal region associates with ribosomes and modulates protein synthesis, and contains two SANT (Myb-like) domains. Through its second SANT domain it binds the serpin SERPINA3/alpha-1-antichymotrypsin and the inter-alpha-trypsin inhibitor heavy chain ITIH4, modulating their protease-inhibitory/processing behavior. DNAJC1 thereby couples the ER-membrane BiP chaperone system to translation and to regulation of secreted protease/protease-inhibitor activity.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0012505 endomembrane system
IBA
GO_REF:0000033 		ACCEPT
Summary: DNAJC1 is an integral ER/nuclear membrane protein and thus acts within the endomembrane system. A general but correct localization.
Reason: Consistent with DNAJC1's documented ER/nuclear/microsomal membrane localization; a broad but accurate site-of-action term.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0001671 ATPase activator activity
IEA
GO_REF:0000117 		ACCEPT
Summary: Rule-based electronic annotation of ATPase activator activity, redundant with the experimentally supported TAS annotation that DNAJC1's lumenal J domain stimulates BiP/HSPA5 ATPase activity.
Reason: J-domain stimulation of BiP ATPase is the core molecular function of DNAJC1 and is supported by experimental TAS evidence; the IEA call is correct.
Supporting Evidence:
PMID:14668352
its lumenal J-domain stimulates the
GO:0005789 endoplasmic reticulum membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: Automated ER-membrane localization derived from the UniProt subcellular-location annotation; DNAJC1 is a single-pass type I ER-membrane protein.
Reason: ER membrane is the correct, documented localization for this single-pass membrane J-protein.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0031965 nuclear membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: Automated nuclear-membrane localization from the UniProt annotation; DNAJC1 is also found in the nuclear (contiguous with ER) membrane.
Reason: Nuclear-membrane localization is documented in UniProt and consistent with DNAJC1's ER/nuclear-envelope membrane residence.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-uniprot.txt
Nucleus membrane
GO:0051246 regulation of protein metabolic process
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Rule-based electronic annotation that DNAJC1 regulates a protein metabolic process, broadly consistent with its roles in BiP-assisted folding, translation modulation and SANT2-mediated protease/secretion regulation.
Reason: A very general process term that subsumes DNAJC1's more specific roles; retained as non-core because the informative functions are captured by specific terms.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-uniprot.txt
May modulate protein synthesis
GO:0005515 protein binding
IPI
PMID:14668352
The SANT2 domain of the murine tumor cell DnaJ-like protein ... 		KEEP AS NON CORE
Summary: Specific interaction of the DNAJC1 SANT2 domain with the serpin SERPINA3/alpha-1-antichymotrypsin (P01011). Bare protein binding is uninformative, but this records a functionally characterized SANT2 interaction.
Reason: Records a real, characterized SANT2-SERPINA3 interaction; bare protein binding is uninformative per curation guidelines, and the functional consequence is captured by the proteolysis/secretion process terms.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:14668352 UniProtKB:P01011
GO:0005515 protein binding
IPI
PMID:28514442
Architecture of the human interactome defines protein commun... 		KEEP AS NON CORE
Summary: Human interactome community study capturing DNAJC1 with RMND1 (Q9NWS8). Bare protein binding is uninformative.
Reason: Records a real high-throughput interaction but bare protein binding is uninformative and the partner does not define DNAJC1's core function.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:28514442 UniProtKB:Q9NWS8
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		KEEP AS NON CORE
Summary: Binary interactome map capturing DNAJC1 with multiple membrane partners (e.g. TNFRSF10C O14798, ATP6V0C P27449, CYP4F2 P78329, AGTRAP, CMTM7, TMEM201, PLP2). Bare protein binding is uninformative.
Reason: Records real high-throughput interactions with membrane proteins but bare protein binding is uninformative; none define DNAJC1's core function.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:O14798
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ... 		KEEP AS NON CORE
Summary: Neurodegeneration interactome screen capturing DNAJC1 with LAMP2 (P13473-2) and SH3GLB1 (Q9Y371). Bare protein binding is uninformative.
Reason: Records real high-throughput interactions but bare protein binding is uninformative and the partners do not define DNAJC1's core function.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32814053 UniProtKB:P13473-2
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		KEEP AS NON CORE
Summary: BioPlex affinity-purification interactome capturing DNAJC1 with RMND1 (Q9NWS8). Bare protein binding is uninformative.
Reason: Records a real high-throughput interaction but bare protein binding is uninformative as a core MF.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q9NWS8
GO:0005515 protein binding
IPI
PMID:35156780
CFTR interactome mapping using the mammalian membrane two-hy... 		KEEP AS NON CORE
Summary: CFTR interactome (membrane two-hybrid) capturing DNAJC1 with CFTR (P13569). Bare protein binding is uninformative, though CFTR is an ER quality-control/ERAD substrate plausibly handled by the BiP/ERdj1 system.
Reason: Records a real interactome interaction with a known ERAD substrate; bare protein binding is uninformative as a core MF.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35156780 UniProtKB:P13569
GO:0005515 protein binding
IPI
PMID:36012204
Differential CFTR-Interactome Proximity Labeling Procedures ... 		KEEP AS NON CORE
Summary: CFTR proximity-labeling interactome again capturing DNAJC1 with CFTR (P13569). Bare protein binding is uninformative.
Reason: Records a real proximity-labeling interaction with CFTR; bare protein binding is uninformative as a core MF.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:36012204 UniProtKB:P13569
GO:0005783 endoplasmic reticulum
IEA
GO_REF:0000107 		ACCEPT
Summary: Ensembl ortholog-projected ER localization, consistent with the experimentally supported ER membrane localization.
Reason: Correct compartment; agrees with ISS/IEA ER membrane evidence.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005886 plasma membrane
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Ensembl ortholog-projected plasma-membrane localization. DNAJC1 is an ER/nuclear-envelope membrane protein; a plasma-membrane localization is not supported and conflicts with its documented topology and residence.
Reason: Orthology-projected plasma-membrane localization conflicts with DNAJC1's established ER/nuclear membrane residence; likely an over-annotation.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-goa.tsv
GO:0005886 plasma membrane cellular_component ECO:0000265 IEA GO_REF:0000107
GO:0051087 protein-folding chaperone binding
IEA
GO_REF:0000107 		ACCEPT
Summary: Orthology-projected chaperone-binding molecular function. DNAJC1's J domain binds the chaperone BiP/HSPA5, so this term is correct.
Reason: DNAJC1 binds the HSP70 chaperone BiP via its J domain; chaperone binding is a genuine molecular function consistent with experimental data.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-uniprot.txt
Interacts (via J domain) with HSPA5
GO:0016020 membrane
HDA
PMID:19946888
Defining the membrane proteome of NK cells. 		KEEP AS NON CORE
Summary: High-throughput membrane-proteome (NK cell) detection of DNAJC1, consistent with its membrane residence but uninformative as to compartment.
Reason: Generic membrane localization from a proteomics screen; correct but less informative than the specific ER/nuclear membrane annotations.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-goa.tsv
GO:0016020 membrane cellular_component ECO:0007005 HDA PMID:19946888
GO:0005515 protein binding
IPI
PMID:16271702
BIP co-chaperone MTJ1/ERDJ1 interacts with inter-alpha-tryps... 		KEEP AS NON CORE
Summary: Specific interaction of the DNAJC1 SANT2 domain with inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4, Q14624); SANT2 protects ITIH4 from kallikrein cleavage. Bare protein binding is uninformative but records a functionally characterized SANT2 interaction.
Reason: Records a real, characterized SANT2-ITIH4 interaction; bare protein binding is uninformative per curation guidelines, with the functional consequence captured by the proteolysis-regulation term.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16271702 UniProtKB:Q14624
GO:0001671 ATPase activator activity
TAS
PMID:14668352
The SANT2 domain of the murine tumor cell DnaJ-like protein ... 		ACCEPT
Summary: The lumenal J domain of DNAJC1/MTJ1 stimulates the ATPase activity of the ER HSP70 chaperone BiP/GRP78. This is the core molecular function of DNAJC1 as a J-protein co-chaperone.
Reason: J-domain stimulation of BiP ATPase is the defining co-chaperone activity of DNAJC1 and is experimentally documented.
Supporting Evidence:
PMID:14668352
its lumenal J-domain stimulates the
GO:0005783 endoplasmic reticulum
ISS
GO_REF:0000024 		ACCEPT
Summary: Sequence/ortholog-based ER localization, consistent with DNAJC1's established ER-membrane residence.
Reason: ISS ER localization agrees with the documented ER membrane localization.
Supporting Evidence:
file:human/DNAJC1/DNAJC1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0045861 negative regulation of proteolysis
TAS
PMID:14668352
The SANT2 domain of the murine tumor cell DnaJ-like protein ... 		KEEP AS NON CORE
Summary: The DNAJC1 SANT2 domain binds SERPINA3/alpha-1-antichymotrypsin and alters its serpin inhibitory activity (and protects ITIH4 from kallikrein cleavage), modulating proteolysis. A documented, specialized process role.
Reason: A genuine, experimentally supported SANT2-mediated function, but specialized/peripheral relative to DNAJC1's core BiP co-chaperone and translation-modulation roles.
Supporting Evidence:
PMID:14668352
results in an apparent loss of ACT inhibitory
GO:0050708 regulation of protein secretion
IDA
PMID:14668352
The SANT2 domain of the murine tumor cell DnaJ-like protein ... 		KEEP AS NON CORE
Summary: DNAJC1's SANT2-mediated modulation of the serpin SERPINA3 is interpreted as regulation of protein secretion. A specialized process role supported by direct experiment.
Reason: Experimentally supported but specialized SANT2-domain function; peripheral to DNAJC1's core co-chaperone/translation-modulation activities.
Supporting Evidence:
PMID:14668352
results in an apparent loss of ACT inhibitory

Core Functions

ER-membrane J-domain co-chaperone whose lumenal J domain stimulates the ATPase activity of the ER HSP70 chaperone BiP (HSPA5), coupling client folding to BiP's ATP cycle at the ER membrane.

Molecular Function:
ATPase activator activity
Cellular Locations:
endoplasmic reticulum membrane
Supporting Evidence:
  • PMID:14668352
    its lumenal J-domain stimulates the
  • file:human/DNAJC1/DNAJC1-uniprot.txt
    Interacts (via J domain) with HSPA5

Binds the ER HSP70 chaperone BiP/HSPA5 (via its J domain) as a co-chaperone; in addition its cytosolic domain associates with ribosomes and is proposed to modulate protein synthesis at the ER membrane.

Molecular Function:
protein-folding chaperone binding
Cellular Locations:
endoplasmic reticulum membrane
Supporting Evidence:
  • file:human/DNAJC1/DNAJC1-uniprot.txt
    Interacts (via J domain) with HSPA5
  • file:human/DNAJC1/DNAJC1-uniprot.txt
    Interacts (via cytosolic domain) with ribosomes

References

GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
PMID:14668352
The SANT2 domain of the murine tumor cell DnaJ-like protein 1 human homologue interacts with alpha1-antichymotrypsin and kinetically interferes with its serpin inhibitory activity.
  • The lumenal J domain of DNAJC1/MTJ1 stimulates the ATPase activity of BiP/GRP78; its cytosolic SANT2 domain binds SERPINA3/alpha-1-antichymotrypsin and interferes with its serpin inhibitory activity.
PMID:16271702
BIP co-chaperone MTJ1/ERDJ1 interacts with inter-alpha-trypsin inhibitor heavy chain 4.
  • The DNAJC1 (MTJ1/ERdj1) SANT2 domain binds ITIH4 and protects an ITIH4 C-terminal fragment from kallikrein cleavage.
PMID:19946888
Defining the membrane proteome of NK cells.
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:35156780
CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.
PMID:36012204
Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters.

Suggested Questions for Experts

Q: How does DNAJC1 ribosome association at the ER membrane mechanistically regulate translation, and is this coupled to BiP-assisted co-translational folding?

Q: What is the physiological significance of the SANT2-mediated regulation of secreted serpins/protease inhibitors (SERPINA3, ITIH4) by an ER-membrane chaperone?

Suggested Experiments

Experiment: Ribosome profiling and polysome analysis in DNAJC1-depleted versus control cells to test its proposed role in translation/protein-synthesis modulation at the ER.

Experiment: Reconstituted BiP ATPase assays with the DNAJC1 lumenal J domain (wild-type versus HPD-motif mutant) to quantify its co-chaperone activity, and co-IP/structural mapping of the cytosolic ribosome-binding region.

📚 Additional Documentation

Notes

(DNAJC1-notes.md)

DNAJC1 (MTJ1 / ERdj1 / HTJ1) research notes

UniProt: Q96KC8. 554 aa, precursor. Single-pass type I ER-membrane protein: lumenal N-term
(48-153) with J-domain (65-129) facing ER lumen; TM 154-174; large cytosolic C-term (175-554)
with two SANT domains (325-379, 492-547) and disordered/phospho-rich region. ER membrane / nuclear
membrane / microsome membrane.

Core function: ER-membrane BiP (HSPA5) co-chaperone + ribosome-associated translation regulator

  • [UniProt FUNCTION "May modulate protein synthesis."] (sparse; By similarity).
  • J domain (lumenal) stimulates BiP/HSPA5 ATPase: PMID:14668352 (citing Chevalier 2000). => GO:0001671 ATPase
    activator activity TAS PMID:14668352. CORE MF.
  • Cytosolic domain interacts with ribosomes (By similarity) — basis of translation/protein-synthesis
    modulation (ERdj1/MTJ1 is the classic ribosome-associated ER membrane J-protein). UniProt SUBUNIT
    "Interacts (via cytosolic domain) with ribosomes (By similarity)."

SANT2 domain functions (serpin/protease regulation)

  • PMID:14668352 SERPINA3/ACT (P01011). => GO:0045861 negative regulation of
    proteolysis TAS; GO:0050708 regulation of protein secretion IDA PMID:14668352.
  • PMID:16271702 ITIH4 (Q14624); SANT2 protects ITIH4 from kallikrein cleavage. Protein binding IPI.

Localization

  • ER membrane (single-pass type I) — CORE. Nuclear membrane, microsome membrane (UniProt). ISS ER.
  • Ensembl-projected plasma membrane (GO:0005886, GO_REF:0000107) — CONFLICTS; DNAJC1 is an
    ER/nuclear membrane protein. MARK_AS_OVER_ANNOTATED.
  • Generic membrane HDA PMID:19946888 (NK membrane proteome) — KEEP_AS_NON_CORE.
  • endomembrane system IBA — ACCEPT (general, correct).

Protein-binding IPIs (mostly HT)

  • SERPINA3/ACT (P01011) PMID:14668352, P80294 — specific SANT2 (functional).
  • ITIH4 (Q14624) PMID:16271702 — specific SANT2 (functional).
  • CFTR (P13569) PMID:35156780, 36012204 — CFTR interactome HT (CFTR is an ERAD substrate, plausible
    client of the BiP/ERdj1 system but HT).
  • RMND1 (Q9NWS8), TNFRSF10C (O14798), ATP6V0C (P27449), CYP4F2, PLP2, etc. PMID:28514442/32296183/
    32814053/33961781 — HT interactome.
    None of the bare protein-binding HT calls are core; KEEP_AS_NON_CORE.

MF/BP assignment

  • Core MF: GO:0001671 ATPase activator activity (lumenal J-domain stimulates BiP ATPase).
  • Core BP: regulation of translation / protein synthesis (ribosome-associated) — GOA has only
    GO:0051246 regulation of protein metabolic process IEA (ARBA); DR line has GO:0006417 regulation of
    translation IEA:Ensembl (not in GOA TSV). The protein-synthesis modulation is the classic ERdj1 role.
  • SANT2 serpin/protease modulation: GO:0045861 neg reg proteolysis, GO:0050708 reg protein secretion —
    genuine but specialized; KEEP_AS_NON_CORE / ACCEPT as documented.

Pn Notes

(DNAJC1-pn-notes.md)

DNAJC1 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q96KC8
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07b
  • Batch change status: added

Source Files Checked

Deep Research Files

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

AIGR Review Snapshot

  • Description: DNAJC1 (MTJ1/ERdj1, human homolog HTJ1) is a single-pass type I endoplasmic reticulum (and nuclear/microsomal) membrane protein of the DNAJC subfamily of J-domain co-chaperones. Its N-terminal J domain faces the ER lumen and stimulates the ATPase activity of the ER HSP70 chaperone BiP (HSPA5), while its large cytosolic C-terminal region associates with ribosomes and modulates protein synthesis, and contains two SANT (Myb-like) domains. Through its second SANT domain it binds the serpin SERPINA3/alpha-1-antichymotrypsin and the inter-alpha-trypsin inhibitor heavy chain ITIH4, modulating their protease-inhibitory/processing behavior. DNAJC1 thereby couples the ER-membrane BiP chaperone system to translation and to regulation of secreted protease/protease-inhibitor activity.
  • Existing/core annotation action counts: ACCEPT: 8; KEEP_AS_NON_CORE: 12; MARK_AS_OVER_ANNOTATED: 1

PN Consistency Summary

  • Consistency: Consistent on the chaperone axis. Notes/YAML describe a single-pass type-I ER-membrane J-protein whose lumenal J domain stimulates BiP/HSPA5 ATPase (GO:0001671 TAS PMID:14668352, ACCEPT/core) and binds BiP (GO:0051087 IEA, ACCEPT). PN "J-domain HSP70 cochaperone" type fits. The review adds two non-chaperone facets PN does not capture (ribosome-associated translation modulation; SANT2-mediated serpin/protease regulation — GO:0045861, GO:0050708) — these are extra, not contradictory.
  • PN story / NEW pressure: PN's HSP70-binding claim is captured (GO:0001671 ATPase activator + GO:0051087 chaperone binding, both ACCEPT/core). PN-projected GO:0030544 (verified real) is narrower than GO:0051087 — defensible specialization since DNAJC1 has TAS evidence its J domain stimulates BiP. No NEW GO term needed for proteostasis. Verdict: already captured.
  • Evidence alignment: Core PMID:14668352 (J-domain→BiP ATPase; SANT2-serpin) and PMID:16271702 (ITIH4) carry the function; PN supplies path context. No conflict; review's many HT-interactome PMIDs (CFTR, RMND1, etc.) are non-core and absent from PN.
  • Verdict: CONSISTENT — GO:0030544 a sound narrower specialization of the verified J-domain→BiP ATPase-stimulating MF; node mapping correct.

Full Consistency Review

  • UniProt: Q96KC8 (MTJ1/ERdj1/HTJ1) · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE
  • PN placement: ER proteostasis|Chaperone|HSP70 system|J-domain containing HSP70 cochaperone (branch ER) ; PN-node mapping: type=mapped, scope=ok_for_propagation_to_go, GO:0030544 Hsp70 protein binding (parents no_mapping)
  • Consistency: Consistent on the chaperone axis. Notes/YAML describe a single-pass type-I ER-membrane J-protein whose lumenal J domain stimulates BiP/HSPA5 ATPase (GO:0001671 TAS PMID:14668352, ACCEPT/core) and binds BiP (GO:0051087 IEA, ACCEPT). PN "J-domain HSP70 cochaperone" type fits. The review adds two non-chaperone facets PN does not capture (ribosome-associated translation modulation; SANT2-mediated serpin/protease regulation — GO:0045861, GO:0050708) — these are extra, not contradictory.
  • PN story / NEW pressure: PN's HSP70-binding claim is captured (GO:0001671 ATPase activator + GO:0051087 chaperone binding, both ACCEPT/core). PN-projected GO:0030544 (verified real) is narrower than GO:0051087 — defensible specialization since DNAJC1 has TAS evidence its J domain stimulates BiP. No NEW GO term needed for proteostasis. Verdict: already captured.
  • Mapping strategy: GO:0030544 mapping is appropriate and does not over-reach — DNAJC1 has direct (TAS) BiP-ATPase-stimulation evidence, a genuine HSP70-cochaperone MF (not an over-broad holdase/unfolded-protein-binding claim). Note the partner is ER HSP70 BiP, consistent with "Hsp70 protein binding."
  • Evidence alignment: Core PMID:14668352 (J-domain→BiP ATPase; SANT2-serpin) and PMID:16271702 (ITIH4) carry the function; PN supplies path context. No conflict; review's many HT-interactome PMIDs (CFTR, RMND1, etc.) are non-core and absent from PN.
  • Verdict: CONSISTENT — GO:0030544 a sound narrower specialization of the verified J-domain→BiP ATPase-stimulating MF; node mapping correct.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/DNAJC1/DNAJC1-ai-review.yaml
  • PN workbook rows: 1

PN row 1: ER proteostasis | Chaperone | HSP70 system | J-domain containing HSP70 cochaperone

  • UniProt: Q96KC8
  • In branches: ER
  • PN-node mapping records (path + ancestors):
    • [type] ER proteostasis|Chaperone|HSP70 system|J-domain containing HSP70 cochaperone
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0030544 Hsp70 protein binding]
      rationale: In the PN hierarchy, this type denotes J-domain cochaperones assigned to the HSP70 system. Their shared mechanistic role is direct interaction with HSP70-family chaperones, making Hsp70 protein binding the most defensible GO target in the current cache.
    • [group] ER proteostasis|Chaperone|HSP70 system
      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] ER proteostasis|Chaperone
      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.
    • [branch] ER 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.

Projected GO annotations (1)

  • GO:0030544 Hsp70 protein binding | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=ER proteostasis|Chaperone|HSP70 system|J-domain containing HSP70 cochaperone

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: Q96KC8
gene_symbol: DNAJC1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: DNAJC1 (MTJ1/ERdj1, human homolog HTJ1) is a single-pass type I endoplasmic
  reticulum (and nuclear/microsomal) membrane protein of the DNAJC subfamily of J-domain
  co-chaperones. Its N-terminal J domain faces the ER lumen and stimulates the ATPase
  activity of the ER HSP70 chaperone BiP (HSPA5), while its large cytosolic C-terminal
  region associates with ribosomes and modulates protein synthesis, and contains two
  SANT (Myb-like) domains. Through its second SANT domain it binds the serpin SERPINA3/alpha-1-antichymotrypsin
  and the inter-alpha-trypsin inhibitor heavy chain ITIH4, modulating their protease-inhibitory/processing
  behavior. DNAJC1 thereby couples the ER-membrane BiP chaperone system to translation
  and to regulation of secreted protease/protease-inhibitor activity.
existing_annotations:
- term:
    id: GO:0012505
    label: endomembrane system
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: DNAJC1 is an integral ER/nuclear membrane protein and thus acts within
      the endomembrane system. A general but correct localization.
    action: ACCEPT
    reason: Consistent with DNAJC1's documented ER/nuclear/microsomal membrane localization;
      a broad but accurate site-of-action term.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0001671
    label: ATPase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: Rule-based electronic annotation of ATPase activator activity, redundant
      with the experimentally supported TAS annotation that DNAJC1's lumenal J domain
      stimulates BiP/HSPA5 ATPase activity.
    action: ACCEPT
    reason: J-domain stimulation of BiP ATPase is the core molecular function of DNAJC1
      and is supported by experimental TAS evidence; the IEA call is correct.
    supported_by:
    - reference_id: PMID:14668352
      supporting_text: its lumenal J-domain stimulates the
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated ER-membrane localization derived from the UniProt subcellular-location
      annotation; DNAJC1 is a single-pass type I ER-membrane protein.
    action: ACCEPT
    reason: ER membrane is the correct, documented localization for this single-pass
      membrane J-protein.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0031965
    label: nuclear membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated nuclear-membrane localization from the UniProt annotation; DNAJC1
      is also found in the nuclear (contiguous with ER) membrane.
    action: ACCEPT
    reason: Nuclear-membrane localization is documented in UniProt and consistent with
      DNAJC1's ER/nuclear-envelope membrane residence.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-uniprot.txt
      supporting_text: Nucleus membrane
- term:
    id: GO:0051246
    label: regulation of protein metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Rule-based electronic annotation that DNAJC1 regulates a protein metabolic
      process, broadly consistent with its roles in BiP-assisted folding, translation
      modulation and SANT2-mediated protease/secretion regulation.
    action: KEEP_AS_NON_CORE
    reason: A very general process term that subsumes DNAJC1's more specific roles;
      retained as non-core because the informative functions are captured by specific
      terms.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-uniprot.txt
      supporting_text: May modulate protein synthesis
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14668352
  qualifier: enables
  review:
    summary: Specific interaction of the DNAJC1 SANT2 domain with the serpin SERPINA3/alpha-1-antichymotrypsin
      (P01011). Bare protein binding is uninformative, but this records a functionally
      characterized SANT2 interaction.
    action: KEEP_AS_NON_CORE
    reason: Records a real, characterized SANT2-SERPINA3 interaction; bare protein
      binding is uninformative per curation guidelines, and the functional consequence
      is captured by the proteolysis/secretion process terms.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:14668352 UniProtKB:P01011
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Human interactome community study capturing DNAJC1 with RMND1 (Q9NWS8).
      Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real high-throughput interaction but bare protein binding is uninformative
      and the partner does not define DNAJC1's core function.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:28514442 UniProtKB:Q9NWS8
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Binary interactome map capturing DNAJC1 with multiple membrane partners
      (e.g. TNFRSF10C O14798, ATP6V0C P27449, CYP4F2 P78329, AGTRAP, CMTM7, TMEM201,
      PLP2). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real high-throughput interactions with membrane proteins but bare
      protein binding is uninformative; none define DNAJC1's core function.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:32296183 UniProtKB:O14798
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Neurodegeneration interactome screen capturing DNAJC1 with LAMP2 (P13473-2)
      and SH3GLB1 (Q9Y371). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real high-throughput interactions but bare protein binding is uninformative
      and the partners do not define DNAJC1's core function.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:32814053 UniProtKB:P13473-2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex affinity-purification interactome capturing DNAJC1 with RMND1
      (Q9NWS8). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real high-throughput interaction but bare protein binding is uninformative
      as a core MF.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:33961781 UniProtKB:Q9NWS8
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35156780
  qualifier: enables
  review:
    summary: CFTR interactome (membrane two-hybrid) capturing DNAJC1 with CFTR (P13569).
      Bare protein binding is uninformative, though CFTR is an ER quality-control/ERAD
      substrate plausibly handled by the BiP/ERdj1 system.
    action: KEEP_AS_NON_CORE
    reason: Records a real interactome interaction with a known ERAD substrate; bare
      protein binding is uninformative as a core MF.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:35156780 UniProtKB:P13569
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36012204
  qualifier: enables
  review:
    summary: CFTR proximity-labeling interactome again capturing DNAJC1 with CFTR (P13569).
      Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real proximity-labeling interaction with CFTR; bare protein binding
      is uninformative as a core MF.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:36012204 UniProtKB:P13569
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl ortholog-projected ER localization, consistent with the experimentally
      supported ER membrane localization.
    action: ACCEPT
    reason: Correct compartment; agrees with ISS/IEA ER membrane evidence.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl ortholog-projected plasma-membrane localization. DNAJC1 is an
      ER/nuclear-envelope membrane protein; a plasma-membrane localization is not supported
      and conflicts with its documented topology and residence.
    action: MARK_AS_OVER_ANNOTATED
    reason: Orthology-projected plasma-membrane localization conflicts with DNAJC1's
      established ER/nuclear membrane residence; likely an over-annotation.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-goa.tsv
      supporting_text: GO:0005886 plasma membrane cellular_component ECO:0000265 IEA
        GO_REF:0000107
- term:
    id: GO:0051087
    label: protein-folding chaperone binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Orthology-projected chaperone-binding molecular function. DNAJC1's J domain
      binds the chaperone BiP/HSPA5, so this term is correct.
    action: ACCEPT
    reason: DNAJC1 binds the HSP70 chaperone BiP via its J domain; chaperone binding
      is a genuine molecular function consistent with experimental data.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-uniprot.txt
      supporting_text: Interacts (via J domain) with HSPA5
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput membrane-proteome (NK cell) detection of DNAJC1, consistent
      with its membrane residence but uninformative as to compartment.
    action: KEEP_AS_NON_CORE
    reason: Generic membrane localization from a proteomics screen; correct but less
      informative than the specific ER/nuclear membrane annotations.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-goa.tsv
      supporting_text: GO:0016020 membrane cellular_component ECO:0007005 HDA PMID:19946888
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16271702
  qualifier: enables
  review:
    summary: Specific interaction of the DNAJC1 SANT2 domain with inter-alpha-trypsin
      inhibitor heavy chain 4 (ITIH4, Q14624); SANT2 protects ITIH4 from kallikrein
      cleavage. Bare protein binding is uninformative but records a functionally characterized
      SANT2 interaction.
    action: KEEP_AS_NON_CORE
    reason: Records a real, characterized SANT2-ITIH4 interaction; bare protein binding
      is uninformative per curation guidelines, with the functional consequence captured
      by the proteolysis-regulation term.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:16271702 UniProtKB:Q14624
- term:
    id: GO:0001671
    label: ATPase activator activity
  evidence_type: TAS
  original_reference_id: PMID:14668352
  qualifier: enables
  review:
    summary: The lumenal J domain of DNAJC1/MTJ1 stimulates the ATPase activity of
      the ER HSP70 chaperone BiP/GRP78. This is the core molecular function of DNAJC1
      as a J-protein co-chaperone.
    action: ACCEPT
    reason: J-domain stimulation of BiP ATPase is the defining co-chaperone activity
      of DNAJC1 and is experimentally documented.
    supported_by:
    - reference_id: PMID:14668352
      supporting_text: its lumenal J-domain stimulates the
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence/ortholog-based ER localization, consistent with DNAJC1's established
      ER-membrane residence.
    action: ACCEPT
    reason: ISS ER localization agrees with the documented ER membrane localization.
    supported_by:
    - reference_id: file:human/DNAJC1/DNAJC1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0045861
    label: negative regulation of proteolysis
  evidence_type: TAS
  original_reference_id: PMID:14668352
  qualifier: involved_in
  review:
    summary: The DNAJC1 SANT2 domain binds SERPINA3/alpha-1-antichymotrypsin and alters
      its serpin inhibitory activity (and protects ITIH4 from kallikrein cleavage),
      modulating proteolysis. A documented, specialized process role.
    action: KEEP_AS_NON_CORE
    reason: A genuine, experimentally supported SANT2-mediated function, but specialized/peripheral
      relative to DNAJC1's core BiP co-chaperone and translation-modulation roles.
    supported_by:
    - reference_id: PMID:14668352
      supporting_text: results in an apparent loss of ACT inhibitory
- term:
    id: GO:0050708
    label: regulation of protein secretion
  evidence_type: IDA
  original_reference_id: PMID:14668352
  qualifier: involved_in
  review:
    summary: DNAJC1's SANT2-mediated modulation of the serpin SERPINA3 is interpreted
      as regulation of protein secretion. A specialized process role supported by direct
      experiment.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported but specialized SANT2-domain function; peripheral
      to DNAJC1's core co-chaperone/translation-modulation activities.
    supported_by:
    - reference_id: PMID:14668352
      supporting_text: results in an apparent loss of ACT inhibitory
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  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
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:14668352
  title: The SANT2 domain of the murine tumor cell DnaJ-like protein 1 human homologue
    interacts with alpha1-antichymotrypsin and kinetically interferes with its serpin
    inhibitory activity.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches PubMed; body confirms DNAJC1/MTJ1/ERdj1's
      lumenal J-domain stimulates BiP/GRP78 ATPase and its SANT2 domain binds
      SERPINA3. GOA anchors this PMID to GO:0001671 (ATPase activator activity, TAS)
      and GO:0050708/GO:0045861, supporting the gene's core ER co-chaperone function.
  findings:
  - statement: The lumenal J domain of DNAJC1/MTJ1 stimulates the ATPase activity of
      BiP/GRP78; its cytosolic SANT2 domain binds SERPINA3/alpha-1-antichymotrypsin
      and interferes with its serpin inhibitory activity.
    reference_section_type: RESULTS
- id: PMID:16271702
  title: BIP co-chaperone MTJ1/ERDJ1 interacts with inter-alpha-trypsin inhibitor
    heavy chain 4.
  findings:
  - statement: The DNAJC1 (MTJ1/ERdj1) SANT2 domain binds ITIH4 and protects an ITIH4
      C-terminal fragment from kallikrein cleavage.
    reference_section_type: RESULTS
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- 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:35156780
  title: CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput
    screening system.
  findings: []
- id: PMID:36012204
  title: Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment
    in Multiple SLC Transporters.
  findings: []
core_functions:
- description: ER-membrane J-domain co-chaperone whose lumenal J domain stimulates
    the ATPase activity of the ER HSP70 chaperone BiP (HSPA5), coupling client folding
    to BiP's ATP cycle at the ER membrane.
  molecular_function:
    id: GO:0001671
    label: ATPase activator activity
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: PMID:14668352
    supporting_text: its lumenal J-domain stimulates the
  - reference_id: file:human/DNAJC1/DNAJC1-uniprot.txt
    supporting_text: Interacts (via J domain) with HSPA5
- description: Binds the ER HSP70 chaperone BiP/HSPA5 (via its J domain) as a co-chaperone;
    in addition its cytosolic domain associates with ribosomes and is proposed to
    modulate protein synthesis at the ER membrane.
  molecular_function:
    id: GO:0051087
    label: protein-folding chaperone binding
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/DNAJC1/DNAJC1-uniprot.txt
    supporting_text: Interacts (via J domain) with HSPA5
  - reference_id: file:human/DNAJC1/DNAJC1-uniprot.txt
    supporting_text: Interacts (via cytosolic domain) with ribosomes
proposed_new_terms: []
suggested_questions:
- question: How does DNAJC1 ribosome association at the ER membrane mechanistically
    regulate translation, and is this coupled to BiP-assisted co-translational folding?
- question: What is the physiological significance of the SANT2-mediated regulation
    of secreted serpins/protease inhibitors (SERPINA3, ITIH4) by an ER-membrane chaperone?
suggested_experiments:
- description: Ribosome profiling and polysome analysis in DNAJC1-depleted versus control
    cells to test its proposed role in translation/protein-synthesis modulation at
    the ER.
- description: Reconstituted BiP ATPase assays with the DNAJC1 lumenal J domain (wild-type
    versus HPD-motif mutant) to quantify its co-chaperone activity, and co-IP/structural
    mapping of the cytosolic ribosome-binding region.