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.
| 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 ... | REMOVE | 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: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Human interactome community study capturing DNAJC1 with RMND1 (Q9NWS8). Bare protein binding is uninformative. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | 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: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Neurodegeneration interactome screen capturing DNAJC1 with LAMP2 (P13473-2) and SH3GLB1 (Q9Y371). Bare protein binding is uninformative. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: BioPlex affinity-purification interactome capturing DNAJC1 with RMND1 (Q9NWS8). Bare protein binding is uninformative. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hy... | REMOVE | 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: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ... | REMOVE | Summary: CFTR proximity-labeling interactome again capturing DNAJC1 with CFTR (P13569). Bare protein binding is uninformative. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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 (UniProt subcellular location); likely an over-annotation. Supporting Evidence: file:human/DNAJC1/DNAJC1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| 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 of isolated NK-cell membranes; correct but less informative than the specific ER/nuclear membrane annotations. Supporting Evidence: PMID:19946888 The present study was initiated to define the composition of the membrane proteome of the Natural Killer (NK) like cell line YTS. file:human/DNAJC1/DNAJC1-uniprot.txt Single-pass type I membrane protein |
| GO:0005515 protein binding | IPI PMID:16271702 BIP co-chaperone MTJ1/ERDJ1 interacts with inter-alpha-tryps... | REMOVE | 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: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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 |
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Download this section (compressed HTML)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?
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.
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