DNAJC14 (DRIP78, "dopamine receptor-interacting protein of 78 kDa"; also HDJ3/hDj-3) is a multi-pass endoplasmic reticulum membrane protein of the DnaJ/HSP40 subfamily C. It contains a cytoplasmically oriented J domain and a family-defining Jiv (Jiv90) domain, and acts as an ER-resident co-chaperone that regulates the export of client membrane proteins from the ER to the cell surface. Its best-characterized client is the dopamine D1 receptor (DRD1), which it binds via an FxxxFxxxF ER-export motif through its C-terminal domain, controlling DRD1 maturation and delivery to the plasma membrane; it has been implicated more broadly in G-protein-coupled receptor trafficking. The Jiv domain is also a host factor exploited during flavivirus/pestivirus RNA replication. DNAJC14 is highly expressed in pancreas and is also expressed in brain, lung, liver, skeletal muscle and kidney.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0050780 dopamine receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation that DNAJC14/DRIP78 binds the dopamine receptor, reflecting its founding role as the dopamine D1 receptor (DRD1)-interacting ER protein that controls DRD1 export. This is the most specific supported molecular function for this gene. Reason: DNAJC14 directly binds DRD1 via the receptor's FxxxFxxxF motif using its C-terminal domain; dopamine receptor binding is a well-supported, specific molecular function and a core activity of the protein. Supporting Evidence: file:human/DNAJC14/DNAJC14-uniprot.txt Interacts with the FxxxFxxxF motif of DRD1 via its C-terminal domain. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Automated SubCell localization to the ER membrane, consistent with DNAJC14 being a multi-pass ER membrane protein. Reason: DNAJC14 is an integral ER membrane protein with three predicted transmembrane helices; ER membrane is its core site of action as an ER-export chaperone. Supporting Evidence: file:human/DNAJC14/DNAJC14-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: High-throughput binary-interactome screen capturing a DNAJC14-SARNP (P82979) interaction. SARNP is a nuclear SAP/RNA-binding protein; the bare protein binding term is uninformative and the partner is unrelated to DNAJC14's ER GPCR-trafficking function. Reason: GO:0005515 is uninformative, and the captured partner (nuclear SARNP) is in a different compartment from this ER membrane protein, suggesting a likely high-throughput artifact rather than a functionally meaningful interaction. Supporting Evidence: file:human/DNAJC14/DNAJC14-uniprot.txt Q6Y2X3; P82979: SARNP; NbExp=3; IntAct=EBI-10038974, EBI-347495; |
| 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 the same DNAJC14-SARNP (P82979) interaction. The bare protein binding term is uninformative. Reason: Uninformative GO:0005515 with a nuclear partner (SARNP) incongruent with DNAJC14's ER membrane localization; likely a high-throughput artifact, not core function. Supporting Evidence: file:human/DNAJC14/DNAJC14-uniprot.txt Q6Y2X3; P82979: SARNP; NbExp=3; IntAct=EBI-10038974, EBI-347495; |
| GO:0001664 G protein-coupled receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic (Ensembl orthology, from rat ortholog Q5XIX0) annotation that DNAJC14 binds a G-protein-coupled receptor. This is the parent generalization of its dopamine D1 receptor binding and is consistent with its broader role in GPCR ER export. Reason: DNAJC14 binds the GPCR DRD1 (and is implicated in trafficking of other GPCRs); the general GPCR-binding term is supported and biologically appropriate, though dopamine receptor binding is the more specific captured activity. Supporting Evidence: file:human/DNAJC14/DNAJC14-uniprot.txt Interacts with the FxxxFxxxF motif of DRD1 via its C-terminal domain. |
| GO:0050780 dopamine receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic (Ensembl orthology) annotation of dopamine receptor binding, redundant with the IBA annotation of the same term and supported by the DRD1 interaction. Reason: Redundant with the IBA dopamine receptor binding annotation and corroborated by the documented DRD1 interaction; a core molecular function. Supporting Evidence: file:human/DNAJC14/DNAJC14-uniprot.txt Interacts with the FxxxFxxxF motif of DRD1 via its C-terminal domain. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: High-throughput proteomics detection of DNAJC14 in a membrane fraction. A generic localization consistent with, but less informative than, the specific ER membrane annotation. Reason: Correct but uninformative generic membrane localization superseded by the specific ER membrane annotation. Supporting Evidence: file:human/DNAJC14/DNAJC14-goa.tsv GO:0016020 membrane cellular_component ECO:0007005 HDA PMID:19946888 |
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Download this section (compressed HTML)Q: Does the DNAJC14 J domain recruit and stimulate an ER-associated HSP70 (e.g. BiP/HSPA5) to chaperone GPCR folding and ER export, and is the HPD motif required for DRD1 surface delivery?
Q: How broad is the DNAJC14 client repertoire beyond DRD1 (which other GPCRs or membrane proteins depend on DRIP78 for ER export), and is selectivity dictated by the FxxxFxxxF motif?
Experiment: Co-immunoprecipitation and surface-biotinylation assays in DNAJC14-knockout cells expressing DRD1 (wild-type versus FxxxFxxxF-motif mutant) to quantify ER retention versus cell-surface delivery.
Experiment: J-domain HPD-motif mutagenesis combined with BiP/HSPA5 ATPase assays to test whether DNAJC14 functions as a bona fide HSP70 co-chaperone in regulating GPCR ER export.
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