DNAJC14

UniProt ID: Q6Y2X3
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

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.

Existing Annotations Review

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

Core Functions

ER-resident DnaJ/HSP40 co-chaperone that binds client G-protein-coupled receptors, notably the dopamine D1 receptor (via its FxxxFxxxF ER-export motif), to regulate their export from the endoplasmic reticulum to the cell surface.

Molecular Function:
dopamine receptor binding
Cellular Locations:
endoplasmic reticulum membrane
Supporting Evidence:
  • file:human/DNAJC14/DNAJC14-uniprot.txt
    Interacts with the FxxxFxxxF motif of DRD1 via its C-terminal domain.
  • file:human/DNAJC14/DNAJC14-uniprot.txt
    Regulates the export of target proteins, such as DRD1, from the endoplasmic reticulum to the cell surface.

References

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 by Ensembl Compara
PMID:19946888
Defining the membrane proteome of NK cells.
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.
file:human/DNAJC14/DNAJC14-uniprot.txt
UniProt entry Q6Y2X3 (DJC14_HUMAN), DnaJ homolog subfamily C member 14 / DRIP78
  • Multi-pass ER membrane J-protein that regulates export of target proteins such as DRD1 from the ER to the cell surface; binds the FxxxFxxxF motif of DRD1 via its C-terminal domain; contains a J domain and a Jiv90 domain.

Suggested Questions for Experts

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?

Suggested Experiments

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.

📚 Additional Documentation

Notes

(DNAJC14-notes.md)

DNAJC14 (DRIP78 / HDJ3) research notes

Identity

  • UniProt Q6Y2X3, HGNC:24581, 702 aa. DnaJ/HSP40 subfamily C member 14.
  • AltNames: DnaJ protein homolog 3 (hDj-3); Dopamine receptor-interacting protein of 78 kDa (DRIP78).
  • Multi-pass ER membrane protein: 3 predicted transmembrane helices (250-270, 300-320, 326-346),
    large disordered N-terminus, J domain at 443-507 (C-terminal half, cytoplasmic side), Jiv90/Jiv
    domain (Pfam PF14901) characteristic of the DNAJC14/Jiv family. [file:human/DNAJC14/DNAJC14-uniprot.txt]

Core function: ER membrane J-protein / GPCR ER export chaperone

  • UniProt FUNCTION: "Regulates the export of target proteins, such as DRD1, from the endoplasmic
    reticulum to the cell surface." (by similarity, ECO:0000250). SUBUNIT: "Interacts with the
    FxxxFxxxF motif of DRD1 via its C-terminal domain." [file:human/DNAJC14/DNAJC14-uniprot.txt]
  • Founding study: Bermak et al. 2001 Nat Cell Biol (PMID:11331877) "Regulation of transport of the
    dopamine D1 receptor by a new membrane-associated ER protein" — identified DRIP78 as ER protein
    controlling DRD1 surface delivery via an FxxxFxxxF ER-export motif. (Title in UniProt ref list.)
  • DRIP78 also implicated in trafficking of other GPCRs (e.g. AT1R/angiotensin receptor) and the
    Ggamma subunit; acts as a chaperone retaining/regulating ER export.

Flavivirus connection (Jiv domain)

  • The Jiv/Jiv90 domain is homologous to the pestivirus NS5A-associated J-domain protein and to the
    region of flaviviral NS3 cofactor; DNAJC14 has been implicated as a host factor that regulates
    flavivirus (e.g. yellow fever, dengue) RNA replication via its J domain. (background; not in GOA)

Localization

  • ER membrane, multi-pass (by similarity). GO:0005789 IEA SubCell. [file:human/DNAJC14/DNAJC14-uniprot.txt]
  • GO:0016020 membrane HDA (bulk proteomics PMID:19946888) — generic, non-core.

GOA annotations

  • GO:0050780 dopamine receptor binding IBA (GO_REF:0000033) and IEA (GO_REF:0000107, from rat ortholog
    Q5XIX0) — supported by DRD1 interaction; core MF.
  • GO:0001664 G protein-coupled receptor binding IEA (rat ortholog) — generalization of DRD1 binding;
    consistent with broader GPCR-trafficking role.
  • GO:0005515 protein binding IPI WITH P82979 (SARNP, a nuclear SAP/RNA-binding protein) from two HT
    screens (PMID:28514442, PMID:33961781) — uninformative; SARNP is nuclear, unrelated to ER GPCR
    trafficking; likely HT artifact. Keep non-core.

Curation decisions

  • Core MF: GPCR-export chaperone. dopamine receptor binding (GO:0050780) is the most specific
    supported MF; GPCR binding (GO:0001664) is the parent. The J-domain HSP70 co-chaperone activity is
    inferred but the functional readout is GPCR ER export. Core: dopamine receptor binding + the BP of
    protein export from ER / protein transport. No experimental human-specific paper cached; rely on
    UniProt (by similarity) and IBA.
  • protein binding with SARNP: MARK_AS_OVER_ANNOTATED / KEEP_AS_NON_CORE (uninformative HT, wrong
    compartment partner).

Pn Notes

(DNAJC14-pn-notes.md)

DNAJC14 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q6Y2X3
  • 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: 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.
  • Existing/core annotation action counts: ACCEPT: 4; KEEP_AS_NON_CORE: 3

PN Consistency Summary

  • Consistency: Tension. PN projects GO:0030544 (Hsp70 binding) as the cochaperone MF. The review and notes describe DNAJC14 as a multi-pass ER-membrane J-protein whose documented function is GPCR ER-export chaperoning (binds DRD1 via FxxxFxxxF motif); the review's core MF is GO:0050780 (dopamine receptor binding) / GO:0001664 (GPCR binding). The review explicitly states the J-domain HSP70-cochaperone activity is inferred but the functional readout is GPCR ER export and there is no cached experimental human paper for a direct HSP70 interaction. GOA contains no GO:0030544 or GO:0031072. So PN's Hsp70-binding claim is unverified for this gene.
  • PN story / NEW pressure: GO:0030544 is verified real but, for DNAJC14, asserts an HSP70 interaction that is neither in GOA nor experimentally cited — the review even lists "does DNAJC14 recruit an ER HSP70" as an open suggested_question. This is over-broad J-domain inference. The gene's actual, supported biology (dopamine/GPCR receptor binding, ER export) is captured (GO:0050780, GO:0001664). No defensible NEW Hsp70 term; the cochaperone MF here is speculative.
  • Evidence alignment: PN carries no titles; review evidence is UniProt (by similarity) + IBA/IEA for DRD1/GPCR binding (PMID:11331877 cited in notes, not GOA; PMID:19946888 only for membrane). No paper supports direct Hsp70 binding. Divergence from PN cochaperone framing.
  • Verdict: PN over-reaches — Hsp70 binding unverified; DNAJC14's supported function is GPCR ER export. Recommended edits: [MAP] do not propagate GO:0030544 to DNAJC14 (mark cochaperone MF unverified); retain GO:0050780 / GO:0001664 as the gene-level MF.

Full Consistency Review

  • UniProt: Q6Y2X3 (DRIP78) · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE
  • PN placement: ER proteostasis|Chaperone|HSP70 system|J-domain containing HSP70 cochaperone ; PN-node mapping: type=mapped, scope=ok_for_propagation_to_go, GO:0030544 Hsp70 protein binding (group/class/branch = no_mapping)
  • Consistency: Tension. PN projects GO:0030544 (Hsp70 binding) as the cochaperone MF. The review and notes describe DNAJC14 as a multi-pass ER-membrane J-protein whose documented function is GPCR ER-export chaperoning (binds DRD1 via FxxxFxxxF motif); the review's core MF is GO:0050780 (dopamine receptor binding) / GO:0001664 (GPCR binding). The review explicitly states the J-domain HSP70-cochaperone activity is inferred but the functional readout is GPCR ER export and there is no cached experimental human paper for a direct HSP70 interaction. GOA contains no GO:0030544 or GO:0031072. So PN's Hsp70-binding claim is unverified for this gene.
  • PN story / NEW pressure: GO:0030544 is verified real but, for DNAJC14, asserts an HSP70 interaction that is neither in GOA nor experimentally cited — the review even lists "does DNAJC14 recruit an ER HSP70" as an open suggested_question. This is over-broad J-domain inference. The gene's actual, supported biology (dopamine/GPCR receptor binding, ER export) is captured (GO:0050780, GO:0001664). No defensible NEW Hsp70 term; the cochaperone MF here is speculative.
  • Mapping strategy: Propagating GO:0030544 to DNAJC14 over-states the evidence (parallel to DNAJC11/DNAJC13 but weaker still — no demonstrated ATPase activator role either). Better to leave DNAJC14's propagating MF as its receptor-binding / ER-export terms and treat the HSP70-cochaperone assignment as unverified.
  • Evidence alignment: PN carries no titles; review evidence is UniProt (by similarity) + IBA/IEA for DRD1/GPCR binding (PMID:11331877 cited in notes, not GOA; PMID:19946888 only for membrane). No paper supports direct Hsp70 binding. Divergence from PN cochaperone framing.
  • Verdict: PN over-reaches — Hsp70 binding unverified; DNAJC14's supported function is GPCR ER export. Recommended edits: [MAP] do not propagate GO:0030544 to DNAJC14 (mark cochaperone MF unverified); retain GO:0050780 / GO:0001664 as the gene-level MF.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/DNAJC14/DNAJC14-ai-review.yaml
  • PN workbook rows: 1

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

  • UniProt: Q6Y2X3
  • 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: Q6Y2X3
gene_symbol: DNAJC14
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
existing_annotations:
- term:
    id: GO:0050780
    label: dopamine receptor binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/DNAJC14/DNAJC14-uniprot.txt
      supporting_text: Interacts with the FxxxFxxxF motif of DRD1 via its C-terminal domain.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated SubCell localization to the ER membrane, consistent with DNAJC14 being a multi-pass ER membrane protein.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/DNAJC14/DNAJC14-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/DNAJC14/DNAJC14-uniprot.txt
      supporting_text: 'Q6Y2X3; P82979: SARNP; NbExp=3; IntAct=EBI-10038974, EBI-347495;'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex affinity-purification interactome capturing the same DNAJC14-SARNP (P82979) interaction. The bare protein binding term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Uninformative GO:0005515 with a nuclear partner (SARNP) incongruent with DNAJC14's ER membrane localization; likely a high-throughput artifact, not core function.
    supported_by:
    - reference_id: file:human/DNAJC14/DNAJC14-uniprot.txt
      supporting_text: 'Q6Y2X3; P82979: SARNP; NbExp=3; IntAct=EBI-10038974, EBI-347495;'
- term:
    id: GO:0001664
    label: G protein-coupled receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/DNAJC14/DNAJC14-uniprot.txt
      supporting_text: Interacts with the FxxxFxxxF motif of DRD1 via its C-terminal domain.
- term:
    id: GO:0050780
    label: dopamine receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Electronic (Ensembl orthology) annotation of dopamine receptor binding, redundant with the IBA annotation of the same term and supported by the DRD1 interaction.
    action: ACCEPT
    reason: Redundant with the IBA dopamine receptor binding annotation and corroborated by the documented DRD1 interaction; a core molecular function.
    supported_by:
    - reference_id: file:human/DNAJC14/DNAJC14-uniprot.txt
      supporting_text: Interacts with the FxxxFxxxF motif of DRD1 via its C-terminal domain.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Correct but uninformative generic membrane localization superseded by the specific ER membrane annotation.
    supported_by:
    - reference_id: file:human/DNAJC14/DNAJC14-goa.tsv
      supporting_text: GO:0016020 membrane cellular_component ECO:0007005 HDA PMID:19946888
references:
- 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 by Ensembl Compara
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Cached; this PMID is cited only for a high-throughput membrane proteomics inclusion (GOA GO:0016020 membrane, HDA) and does not establish DNAJC14's core dopamine-receptor-export function, which in this review rests on the UniProt record rather than any literature PMID present here.
  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: file:human/DNAJC14/DNAJC14-uniprot.txt
  title: UniProt entry Q6Y2X3 (DJC14_HUMAN), DnaJ homolog subfamily C member 14 / DRIP78
  findings:
  - statement: Multi-pass ER membrane J-protein that regulates export of target proteins such as DRD1 from the ER to the cell surface; binds the FxxxFxxxF motif of DRD1 via its C-terminal domain; contains a J domain and a Jiv90 domain.
    reference_section_type: OTHER
core_functions:
- description: ER-resident DnaJ/HSP40 co-chaperone that binds client G-protein-coupled receptors, notably the dopamine D1 receptor (via its FxxxFxxxF ER-export motif), to regulate their export from the endoplasmic reticulum to the cell surface.
  molecular_function:
    id: GO:0050780
    label: dopamine receptor binding
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/DNAJC14/DNAJC14-uniprot.txt
    supporting_text: Interacts with the FxxxFxxxF motif of DRD1 via its C-terminal domain.
  - reference_id: file:human/DNAJC14/DNAJC14-uniprot.txt
    supporting_text: Regulates the export of target proteins, such as DRD1, from the endoplasmic reticulum to the cell surface.
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: 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?
suggested_experiments:
- description: 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.
- description: 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.