DNAJC27

UniProt ID: Q9NZQ0
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

DNAJC27 (RBJ/RABJS; "Rab and DnaJ domain-containing protein") is an unusual chimeric protein combining an N-terminal Ras/Rab-like small-GTPase (P-loop NTPase) domain with a C-terminal DnaJ/J domain, a member of the RJL family. It binds GTP and, in its GTP-bound form, engages the MAP kinase MAP2K1/MEK1 and binds MAPK1/ERK2 through its N-terminal region; nucleus-localized RBJ entraps MEK1/MEK2 in the nucleus and prolongs ERK1/ERK2 activation, acting as a positive regulator/scaffold of the MEK/ERK (MAPK) cascade. Unlike canonical Ras-superfamily GTPases the RJL proteins lack the catalytic glutamine that coordinates GTP hydrolysis, so its intrinsic GTPase activity is uncertain. The C-terminal J domain is predicted to recruit Hsc70/HSP70. DNAJC27 is enhanced in testis, is overexpressed in gastrointestinal cancers, and behaves as an oncogene promoting carcinogenesis and tumor progression.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003924 GTPase activity
IEA
GO_REF:0000120 		MARK AS OVER ANNOTATED
Summary: Electronic/IBA assignment of GTPase activity from the Ras-superfamily domain. However, RJL-family proteins lack the conserved catalytic glutamine required for GTP hydrolysis, and UniProt notes a possible lack of GTPase activity, so catalytic turnover is doubtful for DNAJC27.
Reason: The defining catalytic glutamine of Ras-superfamily GTPases is absent in RJL proteins; GTP binding is supported but hydrolytic GTPase activity is unproven and likely absent.
Supporting Evidence:
PMID:14980719
RJLs lack classical membrane targeting signals and the conserved glutamine residue that coordinates GTP hydrolysis in other proteins from the Ras superfamily.
GO:0005525 GTP binding
IEA
GO_REF:0000002 		ACCEPT
Summary: GTP binding inferred from the conserved P-loop and GTP-binding motifs of the N-terminal Ras/Rab-like domain. The UniProt entry annotates explicit GTP-binding sites.
Reason: The N-terminal domain has intact GTP-binding motifs (P-loop) and is classified in the small-GTPase/Rab family; GTP binding is well supported even though hydrolysis is doubtful.
Supporting Evidence:
file:human/DNAJC27/DNAJC27-uniprot.txt
BINDING 23..30
GO:0005634 nucleus
IEA
GO_REF:0000120 		ACCEPT
Summary: Nuclear localization, consistent with the functionally important nuclear pool of RBJ that entraps MEK1/MEK2 and prolongs ERK activation.
Reason: Nucleus is the functionally relevant compartment for RBJ's MEK/ERK scaffold activity; supported by the ISS annotation and by the experimental nuclear-entrapment mechanism.
Supporting Evidence:
file:human/DNAJC27/DNAJC27-uniprot.txt
SUBCELLULAR LOCATION: Nucleus
GO:0031410 cytoplasmic vesicle
IEA
GO_REF:0000117 		MARK AS OVER ANNOTATED
Summary: ARBA rule-based prediction of cytoplasmic vesicle localization, likely transferred from generic Rab-family membership. Not supported by the documented nuclear localization or function of DNAJC27.
Reason: Generic Rab-family vesicle association predicted by a machine-learning rule; conflicts with the established nuclear localization and is unsupported by experimental data for this protein.
Supporting Evidence:
PMID:14980719
RJLs lack classical membrane targeting signals
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network. 		KEEP AS NON CORE
Summary: Large-scale yeast two-hybrid interactome screen capturing a DNAJC27-TFCP2 interaction. The bare protein binding term is uninformative and not clearly related to RBJ's MEK/ERK function.
Reason: Records a real high-throughput binary interaction (with TFCP2) but bare protein binding is uninformative and not elevated to core.
Supporting Evidence:
file:human/DNAJC27/DNAJC27-uniprot.txt
Q9NZQ0; Q12800: TFCP2; NbExp=6; IntAct=EBI-10317544, EBI-717422
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		KEEP AS NON CORE
Summary: Binary HuRI interactome screen again capturing the DNAJC27-TFCP2 interaction. Bare protein binding, uninformative.
Reason: Corroborates the TFCP2 interaction from a second high-throughput map but remains an uninformative bare-binding annotation.
Supporting Evidence:
file:human/DNAJC27/DNAJC27-uniprot.txt
Q9NZQ0; Q12800: TFCP2; NbExp=6; IntAct=EBI-10317544, EBI-717422
GO:0070374 positive regulation of ERK1 and ERK2 cascade
IEA
GO_REF:0000107 		ACCEPT
Summary: DNAJC27/RBJ positively regulates the ERK1/ERK2 cascade by interacting with MEK1/MEK2 and prolonging the duration of MEK/ERK activation; loss of Rbj attenuates ERK1/2 activation. This is the best-characterized function.
Reason: Strongly supported by the mechanistic study (nuclear entrapment of MEK1/MEK2, prolonged ERK activation, oncogenic transformation) and by the UniProt FUNCTION statement; represents the core biological role.
Supporting Evidence:
PMID:24746703
Nucleus-localized RBJ interacts with MEK/ERK and prolongs the duration of MEK/ERK activation.
GO:0005634 nucleus
ISS
GO_REF:0000024 		ACCEPT
Summary: Sequence/orthology-based nuclear localization (from mouse Q8CFP6), consistent with the functional nuclear pool of RBJ.
Reason: Nucleus is the functionally relevant site of RBJ's MEK/ERK scaffold activity.
Supporting Evidence:
file:human/DNAJC27/DNAJC27-uniprot.txt
SUBCELLULAR LOCATION: Nucleus

Core Functions

Positive regulator/scaffold of the MEK-ERK (MAPK) cascade; GTP-bound DNAJC27 binds MAP2K1/MEK1 and MAPK1/ERK2 and entraps MEK1/MEK2 in the nucleus, prolonging ERK1/ERK2 activation.

Molecular Function:
GTP binding
Cellular Locations:
nucleus
Supporting Evidence:
  • PMID:24746703
    Nucleus-localized RBJ interacts with MEK/ERK and prolongs the duration of MEK/ERK activation.
  • file:human/DNAJC27/DNAJC27-uniprot.txt
    GTPase which can activate the MEK/ERK pathway and induce cell transformation when overexpressed.

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
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
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:14980719
RJLs: a new family of Ras-related GTP-binding proteins.
  • RJL-family proteins lack the conserved catalytic glutamine that coordinates GTP hydrolysis in Ras-superfamily GTPases, and their chordate orthologues are chimeras with C-terminal J domains predicted to recruit Hsc70.
PMID:24746703
Small GTPase RBJ mediates nuclear entrapment of MEK1/MEK2 in tumor progression.
  • Nucleus-localized RBJ interacts with MEK/ERK and prolongs the duration of MEK/ERK activation; Rbj deficiency abrogates nuclear accumulation of MEK1/MEK2 and attenuates ERK1/2 activation, and RBJ is dysregulated in gastrointestinal cancers, acting as an oncogenic Ras-related small GTPase.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:32296183
A reference map of the human binary protein interactome.
file:human/DNAJC27/DNAJC27-uniprot.txt
UniProt entry Q9NZQ0 (DJC27_HUMAN), DnaJ homolog subfamily C member 27 (RBJ)
  • Chimeric Ras/Rab-like GTPase plus C-terminal J domain; binds GTP and (in GTP-bound form) MAP2K1, interacts with MAPK1 via N-terminal region; nuclear; activates the MEK/ERK pathway and can induce cell transformation when overexpressed.

Suggested Questions for Experts

Q: Does human DNAJC27 retain any catalytic GTPase activity despite lacking the canonical catalytic glutamine, or does it function purely as a GTP-loaded conformational switch/scaffold?

Q: Is the C-terminal J domain of DNAJC27 a functional Hsc70/HSP70 co-chaperone (stimulating ATPase activity), and does Hsc70 recruitment contribute to MEK/ERK scaffolding?

Suggested Experiments

Experiment: Recombinant GTP-hydrolysis and nucleotide-exchange assays on the DNAJC27 GTPase domain (wild-type vs catalytic-residue mutants) to determine whether it hydrolyzes GTP.

Experiment: J-domain HSP70 ATPase-stimulation assay and HPD-motif mutagenesis to test whether DNAJC27 acts as a bona fide Hsc70 co-chaperone.

Experiment: Domain-dissection co-immunoprecipitation and live-cell imaging to map which RBJ domain mediates nuclear MEK1/MEK2 entrapment and to test the GTP-dependence of the MEK/ERK interactions.

📚 Additional Documentation

Notes

(DNAJC27-notes.md)

DNAJC27 (RBJ / RABJS) research notes

Identity

  • UniProt Q9NZQ0 (DJC27_HUMAN), 273 aa. HGNC:30290. Synonyms RABJS, RBJ. "Rab and DnaJ domain-containing protein".
  • Chimeric protein: N-terminal Ras/Rab-like small-GTPase (P-loop NTPase) domain + C-terminal J domain (residues 217-273). Member of the RJL family (Ras-related + J-domain-like).

Function

  • GTPase that can activate the MEK/ERK pathway and induce cell transformation when overexpressed; may act as a nuclear scaffold for MAPK1/ERK2.
    [UniProt FUNCTION (by similarity to mouse Q8CFP6): "GTPase which can activate the MEK/ERK pathway and induce cell transformation when overexpressed. May act as a nuclear scaffold for MAPK1..."]
  • RBJ mediates nuclear entrapment of MEK1/MEK2 and prolongs ERK1/2 activation, promoting gastrointestinal carcinogenesis.
    PMID:24746703
  • Interacts directly with MAPK1 (N-terminal region 1-18 required) and with MAP2K1/MEK1 in GTP-bound form (UniProt SUBUNIT).

GTPase caveat (important)

  • The RJL family lacks the conserved catalytic glutamine that coordinates GTP hydrolysis in canonical Ras-superfamily GTPases.
    PMID:14980719
  • UniProt reference [5] is annotated "IDENTIFICATION, AND POSSIBLE LACK OF GTPASE ACTIVITY." So GTP binding is supported but catalytic GTPase activity is doubtful — the IBA/IEA "GTPase activity" annotations are likely over-annotations; "GTP binding" is on firmer ground.

J domain / Hsc70

  • The C-terminal J domain is predicted to recruit Hsc70/HSP70.
    PMID:14980719
  • Original cloning ref (Chen et al. 2002, submitted) titled "a unique Rab GTPase containing a J domain that interacts with Hsc70." However, no detailed experimental characterization of canonical HSP70 co-chaperone (ATPase-stimulating) activity for human DNAJC27 is established.

Localization

  • Nucleus (by similarity to mouse; ISS). IEA also cytoplasmic vesicle (ARBA) and organelle membrane — weakly supported / generic.
  • Tissue enhanced in testis (HPA); overexpressed in GI cancers (PMID:24746703).

Interactome

  • TFCP2 (Q12800) is the only curated IPI partner, from two large interactome screens (PMID:25416956 Y2H proteome map; PMID:32296183 HuRI binary interactome). Bare protein binding; not clearly tied to RBJ's MEK/ERK function.

GO annotation review reasoning

  • GTP binding (IEA, InterPro) — ACCEPT (P-loop, GTP-binding motifs present; KW GTP-binding).
  • GTPase activity (IBA/IEA) — likely over-annotated given lack of catalytic glutamine; MARK_AS_OVER_ANNOTATED.
  • nucleus (ISS/IEA) — ACCEPT (functionally relevant; nuclear MEK/ERK scaffold).
  • positive regulation of ERK1 and ERK2 cascade (IEA from mouse ortholog) — ACCEPT/core; this is the best-characterized function.
  • cytoplasmic vesicle / organelle membrane (IEA ARBA) — weakly supported, KEEP_AS_NON_CORE or over-annotated.
  • protein binding (IPI, TFCP2) — KEEP_AS_NON_CORE (uninformative bare term).
  • Core MF: this protein is best described as a J-domain GTP-binding scaffold acting in MEK/ERK signaling. No clean MF GO term beyond GTP binding; for biological process, positive regulation of ERK1/ERK2 cascade is core.

Pn Notes

(DNAJC27-pn-notes.md)

DNAJC27 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9NZQ0
  • 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: DNAJC27 (RBJ/RABJS; "Rab and DnaJ domain-containing protein") is an unusual chimeric protein combining an N-terminal Ras/Rab-like small-GTPase (P-loop NTPase) domain with a C-terminal DnaJ/J domain, a member of the RJL family. It binds GTP and, in its GTP-bound form, engages the MAP kinase MAP2K1/MEK1 and binds MAPK1/ERK2 through its N-terminal region; nucleus-localized RBJ entraps MEK1/MEK2 in the nucleus and prolongs ERK1/ERK2 activation, acting as a positive regulator/scaffold of the MEK/ERK (MAPK) cascade. Unlike canonical Ras-superfamily GTPases the RJL proteins lack the catalytic glutamine that coordinates GTP hydrolysis, so its intrinsic GTPase activity is uncertain. The C-terminal J domain is predicted to recruit Hsc70/HSP70. DNAJC27 is enhanced in testis, is overexpressed in gastrointestinal cancers, and behaves as an oncogene promoting carcinogenesis and tumor progression.
  • Existing/core annotation action counts: ACCEPT: 4; KEEP_AS_NON_CORE: 2; MARK_AS_OVER_ANNOTATED: 2

PN Consistency Summary

  • Consistency: PARTIAL TENSION. Deep research and review YAML converge on RBJ as a chimeric Ras/Rab-GTPase + J-domain protein whose CHARACTERIZED function is a GTP-bound MEK/ERK scaffold/positive regulator (core MF GO:0005525 GTP binding; core BP GO:0070374 ERK cascade), oncogenic in GI cancer. The C-terminal J-domain is only PREDICTED to recruit Hsc70/HSP70 (PMID:14980719), with no experimental HSP70-cochaperone characterization. The PN node files RBJ purely as a "J-domain HSP70 cochaperone," which captures the J-domain but omits its dominant, evidence-backed GTPase/ERK identity — a placement/emphasis mismatch, not a hard contradiction.
  • PN story / NEW pressure: PN asserts GO:0030544 Hsp70 protein binding (verified real). GOA lacks any HSP70/chaperone-binding term, so the "more_specific_than_existing_goa" label is loose — there is nothing in GOA for it to be more specific than; functionally it is new_to_goa. GO:0030544 is defensible only as a domain-level prediction; over-reaches if presented as a core function, since the gene's real MF is GTP binding / ERK scaffolding.
  • Evidence alignment: PN row carries no titles; review cites PMID:14980719 (RJL family, J-domain prediction) and PMID:24746703 (nuclear MEK/ERK entrapment) — both VERIFIED. The HSP70-binding story rests only on the family prediction; no shared experimental paper supports it.
  • Verdict: Consistent core review; PN placement over-emphasizes the J-domain. GO:0030544 is a defensible inferred ADD but not core. Recommended edits: [MAP] change goa_status from more_specific_than_existing_goa to new_to_goa (no existing chaperone-binding GOA term to refine).

Full Consistency Review

  • UniProt: Q9NZQ0 (RBJ / RABJS) · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE
  • PN placement: Cytonuclear 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 (projected more_specific_than_existing_goa); group/class/branch=no_mapping.
  • Consistency: PARTIAL TENSION. Deep research and review YAML converge on RBJ as a chimeric Ras/Rab-GTPase + J-domain protein whose CHARACTERIZED function is a GTP-bound MEK/ERK scaffold/positive regulator (core MF GO:0005525 GTP binding; core BP GO:0070374 ERK cascade), oncogenic in GI cancer. The C-terminal J-domain is only PREDICTED to recruit Hsc70/HSP70 (PMID:14980719), with no experimental HSP70-cochaperone characterization. The PN node files RBJ purely as a "J-domain HSP70 cochaperone," which captures the J-domain but omits its dominant, evidence-backed GTPase/ERK identity — a placement/emphasis mismatch, not a hard contradiction.
  • PN story / NEW pressure: PN asserts GO:0030544 Hsp70 protein binding (verified real). GOA lacks any HSP70/chaperone-binding term, so the "more_specific_than_existing_goa" label is loose — there is nothing in GOA for it to be more specific than; functionally it is new_to_goa. GO:0030544 is defensible only as a domain-level prediction; over-reaches if presented as a core function, since the gene's real MF is GTP binding / ERK scaffolding.
  • Mapping strategy: Node status unchanged. goa_status flag ("more_specific_than_existing_goa") should be new_to_goa. The projected term is domain-inferred, not characterized — keep IBA/IEA strength, do not elevate to core.
  • Evidence alignment: PN row carries no titles; review cites PMID:14980719 (RJL family, J-domain prediction) and PMID:24746703 (nuclear MEK/ERK entrapment) — both VERIFIED. The HSP70-binding story rests only on the family prediction; no shared experimental paper supports it.
  • Verdict: Consistent core review; PN placement over-emphasizes the J-domain. GO:0030544 is a defensible inferred ADD but not core. Recommended edits: [MAP] change goa_status from more_specific_than_existing_goa to new_to_goa (no existing chaperone-binding GOA term to refine).

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/DNAJC27/DNAJC27-ai-review.yaml
  • PN workbook rows: 1

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

  • UniProt: Q9NZQ0
  • In branches: CY
  • PN-node mapping records (path + ancestors):
    • [type] Cytonuclear 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] 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.

Projected GO annotations (1)

  • GO:0030544 Hsp70 protein binding | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Cytonuclear 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: Q9NZQ0
gene_symbol: DNAJC27
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: DNAJC27 (RBJ/RABJS; "Rab and DnaJ domain-containing protein") is an unusual
  chimeric protein combining an N-terminal Ras/Rab-like small-GTPase (P-loop NTPase)
  domain with a C-terminal DnaJ/J domain, a member of the RJL family. It binds GTP
  and, in its GTP-bound form, engages the MAP kinase MAP2K1/MEK1 and binds MAPK1/ERK2
  through its N-terminal region; nucleus-localized RBJ entraps MEK1/MEK2 in the nucleus
  and prolongs ERK1/ERK2 activation, acting as a positive regulator/scaffold of the
  MEK/ERK (MAPK) cascade. Unlike canonical Ras-superfamily GTPases the RJL proteins
  lack the catalytic glutamine that coordinates GTP hydrolysis, so its intrinsic GTPase
  activity is uncertain. The C-terminal J domain is predicted to recruit Hsc70/HSP70.
  DNAJC27 is enhanced in testis, is overexpressed in gastrointestinal cancers, and
  behaves as an oncogene promoting carcinogenesis and tumor progression.
alternative_products:
- name: '1'
  id: Q9NZQ0-1
- name: '2'
  id: Q9NZQ0-2
  sequence_note: VSP_033409, VSP_033410
- name: '3'
  id: Q9NZQ0-3
  sequence_note: VSP_033411, VSP_033412
existing_annotations:
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic/IBA assignment of GTPase activity from the Ras-superfamily
      domain. However, RJL-family proteins lack the conserved catalytic glutamine
      required for GTP hydrolysis, and UniProt notes a possible lack of GTPase activity,
      so catalytic turnover is doubtful for DNAJC27.
    action: MARK_AS_OVER_ANNOTATED
    reason: The defining catalytic glutamine of Ras-superfamily GTPases is absent in
      RJL proteins; GTP binding is supported but hydrolytic GTPase activity is unproven
      and likely absent.
    supported_by:
    - reference_id: PMID:14980719
      supporting_text: RJLs lack classical membrane targeting signals and the conserved
        glutamine residue that coordinates GTP hydrolysis in other proteins from the
        Ras superfamily.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: GTP binding inferred from the conserved P-loop and GTP-binding motifs
      of the N-terminal Ras/Rab-like domain. The UniProt entry annotates explicit
      GTP-binding sites.
    action: ACCEPT
    reason: The N-terminal domain has intact GTP-binding motifs (P-loop) and is classified
      in the small-GTPase/Rab family; GTP binding is well supported even though hydrolysis
      is doubtful.
    supported_by:
    - reference_id: file:human/DNAJC27/DNAJC27-uniprot.txt
      supporting_text: BINDING         23..30
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Nuclear localization, consistent with the functionally important nuclear
      pool of RBJ that entraps MEK1/MEK2 and prolongs ERK activation.
    action: ACCEPT
    reason: Nucleus is the functionally relevant compartment for RBJ's MEK/ERK scaffold
      activity; supported by the ISS annotation and by the experimental nuclear-entrapment
      mechanism.
    supported_by:
    - reference_id: file:human/DNAJC27/DNAJC27-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Nucleus'
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: ARBA rule-based prediction of cytoplasmic vesicle localization, likely
      transferred from generic Rab-family membership. Not supported by the documented
      nuclear localization or function of DNAJC27.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic Rab-family vesicle association predicted by a machine-learning
      rule; conflicts with the established nuclear localization and is unsupported
      by experimental data for this protein.
    supported_by:
    - reference_id: PMID:14980719
      supporting_text: RJLs lack classical membrane targeting signals
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Large-scale yeast two-hybrid interactome screen capturing a DNAJC27-TFCP2
      interaction. The bare protein binding term is uninformative and not clearly
      related to RBJ's MEK/ERK function.
    action: KEEP_AS_NON_CORE
    reason: Records a real high-throughput binary interaction (with TFCP2) but bare
      protein binding is uninformative and not elevated to core.
    supported_by:
    - reference_id: file:human/DNAJC27/DNAJC27-uniprot.txt
      supporting_text: 'Q9NZQ0; Q12800: TFCP2; NbExp=6; IntAct=EBI-10317544, EBI-717422'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Binary HuRI interactome screen again capturing the DNAJC27-TFCP2 interaction.
      Bare protein binding, uninformative.
    action: KEEP_AS_NON_CORE
    reason: Corroborates the TFCP2 interaction from a second high-throughput map but
      remains an uninformative bare-binding annotation.
    supported_by:
    - reference_id: file:human/DNAJC27/DNAJC27-uniprot.txt
      supporting_text: 'Q9NZQ0; Q12800: TFCP2; NbExp=6; IntAct=EBI-10317544, EBI-717422'
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: DNAJC27/RBJ positively regulates the ERK1/ERK2 cascade by interacting
      with MEK1/MEK2 and prolonging the duration of MEK/ERK activation; loss of Rbj
      attenuates ERK1/2 activation. This is the best-characterized function.
    action: ACCEPT
    reason: Strongly supported by the mechanistic study (nuclear entrapment of MEK1/MEK2,
      prolonged ERK activation, oncogenic transformation) and by the UniProt FUNCTION
      statement; represents the core biological role.
    supported_by:
    - reference_id: PMID:24746703
      supporting_text: Nucleus-localized RBJ interacts with MEK/ERK and prolongs the
        duration of MEK/ERK activation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence/orthology-based nuclear localization (from mouse Q8CFP6), consistent
      with the functional nuclear pool of RBJ.
    action: ACCEPT
    reason: Nucleus is the functionally relevant site of RBJ's MEK/ERK scaffold activity.
    supported_by:
    - reference_id: file:human/DNAJC27/DNAJC27-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Nucleus'
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- 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: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: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:14980719
  title: 'RJLs: a new family of Ras-related GTP-binding proteins.'
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publication title matches the YAML title; the text defines the RJL family of Ras-related GTP-binding proteins (DNAJC27/RBJ) and notes the chordate chimeric architecture with a C-terminal J domain, supporting the GTP-binding molecular function and J-domain co-chaperone framing of this gene."
  findings:
  - statement: RJL-family proteins lack the conserved catalytic glutamine that coordinates
      GTP hydrolysis in Ras-superfamily GTPases, and their chordate orthologues are
      chimeras with C-terminal J domains predicted to recruit Hsc70.
    reference_section_type: ABSTRACT
- id: PMID:24746703
  title: Small GTPase RBJ mediates nuclear entrapment of MEK1/MEK2 in tumor progression.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publication title matches the YAML title; the text shows nucleus-localized RBJ (DNAJC27) interacts with MEK/ERK and prolongs MEK/ERK activation, with Rbj deficiency abrogating nuclear MEK1/MEK2 accumulation. Primary experimental reference for the MEK-ERK scaffold/positive-regulator core function; cited in core_functions.supported_by."
  findings:
  - statement: Nucleus-localized RBJ interacts with MEK/ERK and prolongs the duration
      of MEK/ERK activation; Rbj deficiency abrogates nuclear accumulation of MEK1/MEK2
      and attenuates ERK1/2 activation, and RBJ is dysregulated in gastrointestinal
      cancers, acting as an oncogenic Ras-related small GTPase.
    reference_section_type: ABSTRACT
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: file:human/DNAJC27/DNAJC27-uniprot.txt
  title: UniProt entry Q9NZQ0 (DJC27_HUMAN), DnaJ homolog subfamily C member 27 (RBJ)
  findings:
  - statement: Chimeric Ras/Rab-like GTPase plus C-terminal J domain; binds GTP and
      (in GTP-bound form) MAP2K1, interacts with MAPK1 via N-terminal region; nuclear;
      activates the MEK/ERK pathway and can induce cell transformation when overexpressed.
    reference_section_type: OTHER
core_functions:
- description: Positive regulator/scaffold of the MEK-ERK (MAPK) cascade; GTP-bound
    DNAJC27 binds MAP2K1/MEK1 and MAPK1/ERK2 and entraps MEK1/MEK2 in the nucleus,
    prolonging ERK1/ERK2 activation.
  molecular_function:
    id: GO:0005525
    label: GTP binding
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:24746703
    supporting_text: Nucleus-localized RBJ interacts with MEK/ERK and prolongs the
      duration of MEK/ERK activation.
  - reference_id: file:human/DNAJC27/DNAJC27-uniprot.txt
    supporting_text: GTPase which can activate the MEK/ERK pathway and induce cell
      transformation when overexpressed.
proposed_new_terms: []
suggested_questions:
- question: Does human DNAJC27 retain any catalytic GTPase activity despite lacking
    the canonical catalytic glutamine, or does it function purely as a GTP-loaded
    conformational switch/scaffold?
- question: Is the C-terminal J domain of DNAJC27 a functional Hsc70/HSP70 co-chaperone
    (stimulating ATPase activity), and does Hsc70 recruitment contribute to MEK/ERK
    scaffolding?
suggested_experiments:
- description: Recombinant GTP-hydrolysis and nucleotide-exchange assays on the DNAJC27
    GTPase domain (wild-type vs catalytic-residue mutants) to determine whether it
    hydrolyzes GTP.
- description: J-domain HSP70 ATPase-stimulation assay and HPD-motif mutagenesis to
    test whether DNAJC27 acts as a bona fide Hsc70 co-chaperone.
- description: Domain-dissection co-immunoprecipitation and live-cell imaging to map
    which RBJ domain mediates nuclear MEK1/MEK2 entrapment and to test the GTP-dependence
    of the MEK/ERK interactions.