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.