id: Q9BX63
gene_symbol: BRIP1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  BRIP1 (Fanconi anemia group J protein, FANCJ; formerly BACH1/BRCA1-associated
  C-terminal helicase 1) is an ATP-dependent 5'-to-3' DNA helicase of the
  Rad3/XPD (DinG) superfamily 2 subfamily. It is a DNA-dependent ATPase that
  couples ATP hydrolysis to translocation along ssDNA and unwinding of duplex
  DNA, and it requires a [4Fe-4S] iron-sulfur cluster for helicase activity. The
  enzyme preferentially engages forked duplex substrates with a 5' single-stranded
  tail and can resolve non-B DNA structures, most notably G-quadruplexes, thereby
  removing replication-fork roadblocks and safeguarding genome stability. BRIP1
  functions in homologous recombination repair of DNA double-strand breaks in
  concert with BRCA1, to whose C-terminal BRCT domains it binds in a
  phosphorylation-dependent manner (via phospho-Ser990), and it acts late in the
  Fanconi anemia interstrand crosslink (ICL) repair pathway, after FANCD2
  ubiquitination, where its direct interaction with the mismatch-repair
  MutLalpha component MLH1 is required to correct the crosslink response. At
  stalled or damaged replication forks it collaborates with RPA and BLM and
  promotes repair of DNA-protein crosslinks by using its ATPase to unfold the
  protein adduct, exposing the underlying DNA for cleavage by the SPRTN protease.
  BRIP1 localizes chiefly to the nucleoplasm and forms DNA-damage-inducible
  nuclear foci; its Fe-S cluster is matured by the cytosolic iron-sulfur assembly
  (CIA) machinery (CIAO1, CIAO2B, MMS19), consistent with a minor cytoplasmic
  pool. Biallelic loss-of-function causes Fanconi anemia complementation group J,
  and monoallelic pathogenic variants confer susceptibility to breast and ovarian
  cancer.
alternative_products:
- name: '1'
  id: Q9BX63-1
- name: '2'
  id: Q9BX63-2
  sequence_note: VSP_012540, VSP_012541
existing_annotations:
- term:
    id: GO:0003678
    label: DNA helicase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) inference that BRIP1 enables DNA helicase activity, from
      the Rad3/XPD helicase family tree. This is correct but generic; BRIP1 is
      specifically a 5'-3' DNA helicase (GO:0043139), annotated separately with
      experimental support.
    action: ACCEPT
    reason: >-
      BRIP1 is a bona fide ATP-dependent DNA helicase, directly demonstrated
      biochemically. The parent term "DNA helicase activity" is accurate at a
      general level; the more specific 5'-3' directionality is captured by
      GO:0043139 elsewhere in the annotation set.
    supported_by:
    - reference_id: PMID:14983014
      supporting_text: we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic inference that BRIP1 is active in the nucleus. Consistent with
      its role as a nuclear DNA repair/replication helicase.
    action: ACCEPT
    reason: >-
      BRIP1 acts on nuclear DNA in HR, ICL and DPC repair, and forms nuclear
      DNA-damage foci. Nuclear localization is well supported experimentally.
    supported_by:
    - reference_id: PMID:17596542
      supporting_text: dependent on the presence of BRCA1, FANCJ colocalizes with RPA in nuclear foci after DNA damage
- term:
    id: GO:0006289
    label: nucleotide-excision repair
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      IBA inference of involvement in nucleotide-excision repair, propagated from
      the Rad3/XPD family (which includes the NER helicase XPD). There is no
      FANCJ-specific evidence that BRIP1 participates in classical NER.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      BRIP1/FANCJ's characterized biological roles are interstrand-crosslink
      repair, homologous recombination, DNA-protein-crosslink repair, and
      G-quadruplex resolution — not the classical NER pathway performed by its
      paralog XPD. The term appears to be over-propagated across the helicase
      family tree rather than reflecting a demonstrated FANCJ function.
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - FUNCTIONAL_DIVERGENCE
      source_entities:
      - source_id: UniProtKB:P18074
        comment: >-
          XPD (ERCC2) is the Rad3/XPD-family paralog that performs nucleotide-excision
          repair; FANCJ diverged to ICL/HR/DPC/G4 functions and is not a NER factor.
- term:
    id: GO:1990918
    label: double-strand break repair involved in meiotic recombination
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      IBA inference (from mouse/worm homologs) of a role in meiotic
      recombination-associated DSB repair. BRIP1 is highly expressed in testis,
      making a meiotic role plausible, but this is not an established core somatic
      function in human. Supported at the ortholog level: Fancj (GT/GT) mice show
      altered processing of meiotic crossover sites during prophase I (increased
      MLH1 focus frequency and chiasmata), consistent with a role in the DSB-repair
      events of meiotic recombination.
    action: KEEP_AS_NON_CORE
    reason: >-
      Plausible for the family and consistent with testis-enriched expression, but
      the human gene's characterized, disease-relevant functions are somatic
      genome-maintenance activities (ICL/HR/DPC repair). Retained as a non-core,
      context-specific process.
    supported_by:
    - reference_id: PMID:26490168
      supporting_text: indicative of increased DSB repair via CO
    - reference_id: PMID:26490168
      supporting_text: MLH1 focus frequency is increased in Fancj (GT/GT) males
- term:
    id: GO:0003676
    label: nucleic acid binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro-based electronic annotation of generic nucleic acid binding. True
      but uninformative; BRIP1 binds DNA specifically.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Nucleic acid binding" is a high-level parent that adds little; the specific
      and informative activity is DNA binding / DNA helicase activity, which are
      separately annotated.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro-based inference of DNA binding. Correct and relevant — BRIP1 binds
      and translocates on DNA as part of its helicase mechanism.
    action: ACCEPT
    reason: >-
      DNA binding is experimentally supported (substrate binding/unwinding assays)
      and is a genuine molecular capability of the enzyme.
    supported_by:
    - reference_id: PMID:15878853
      supporting_text: BACH1 preferentially binds and unwinds a forked duplex substrate
- term:
    id: GO:0003678
    label: DNA helicase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro-based inference of DNA helicase activity. Correct but generic
      relative to the experimentally established 5'-3' directionality.
    action: ACCEPT
    reason: >-
      Consistent with the experimentally demonstrated helicase activity of BRIP1.
    supported_by:
    - reference_id: PMID:14983014
      supporting_text: we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase
- term:
    id: GO:0004386
    label: helicase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro-based inference of generic helicase activity, a parent of DNA
      helicase activity.
    action: ACCEPT
    reason: >-
      Correct high-level term; the more specific DNA/5'-3' helicase terms are
      annotated separately with experimental support.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro-based inference of ATP binding. Supported by the Walker A/ATP-binding
      motif and by the DNA-dependent ATPase activity of the protein.
    action: ACCEPT
    reason: >-
      BRIP1 contains a helicase ATP-binding domain (residues 11-442, ATP-binding
      site 185-192) and hydrolyzes ATP; ATP binding is a prerequisite for its
      motor activity.
    supported_by:
    - reference_id: PMID:14983014
      supporting_text: ATP binding and hydrolysis are prerequisites for the strand separation activity of all known helicases
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      UniProt subcellular-location keyword mapping to nucleus. Correct.
    action: ACCEPT
    reason: >-
      Nuclear localization of BRIP1 is well established experimentally.
    supported_by:
    - reference_id: PMID:17596542
      supporting_text: FANCJ colocalizes with RPA in nuclear foci after DNA damage
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      UniProt subcellular-location keyword mapping to cytoplasm. BRIP1 has a minor
      cytoplasmic pool, consistent with maturation of its Fe-S cluster by the
      cytosolic iron-sulfur assembly (CIA) machinery.
    action: KEEP_AS_NON_CORE
    reason: >-
      A cytoplasmic pool is documented (interaction with CIAO1/CIAO2B/MMS19), but
      BRIP1's functional site of action is nuclear; cytoplasmic localization is a
      non-core, cofactor-maturation-related compartment.
    supported_by:
    - reference_id: PMID:23585563
      supporting_text: IOP1 functions in the MMS19-dependent CIA pathway
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      ARBA machine-learning electronic annotation of involvement in DNA repair.
      Correct at a general level.
    action: ACCEPT
    reason: >-
      BRIP1 is a core genome-maintenance/DNA-repair factor; the general term is
      accurate, with more specific processes (HR, ICL, DPC repair) annotated
      elsewhere.
    supported_by:
    - reference_id: PMID:11301010
      supporting_text: contributes to its DNA repair function
- term:
    id: GO:0016818
    label: hydrolase activity, acting on acid anhydrides, in phosphorus-containing
      anhydrides
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro-based inference of a high-level phosphoanhydride hydrolase activity,
      a distant parent of ATP hydrolysis activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Overly general; the informative and experimentally supported activity is
      ATP hydrolysis activity (GO:0016887), annotated separately.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: >-
      RHEA/Rhea-mapping electronic annotation of ATP hydrolysis activity. Correct
      and experimentally corroborated (DNA-dependent ATPase).
    action: ACCEPT
    reason: >-
      BRIP1 is a DNA-dependent ATPase; ATP hydrolysis fuels its translocase/helicase
      activity.
    supported_by:
    - reference_id: PMID:14983014
      supporting_text: These results indicate that BACH1 possesses an intrinsic, DNA-dependent ATPase activity
- term:
    id: GO:0043139
    label: 5'-3' DNA helicase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: >-
      EC 5.6.2.3 mapping to 5'-3' DNA helicase activity. This is BRIP1's core
      molecular function and is strongly supported experimentally.
    action: ACCEPT
    reason: >-
      Directly demonstrated: BRIP1 translocates 5'-to-3' and unwinds duplex DNA in
      an ATP-dependent manner.
    supported_by:
    - reference_id: PMID:14983014
      supporting_text: indicating translocation in the 5′-to-3′ direction with respect to the strand to which the enzyme is bound
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15125843
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation capturing the direct BRIP1-BRCA1 interaction
      (structure of BRCA1 BRCT repeats bound to a BACH1 phosphopeptide; partner
      BRCA1/P38398).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Per curation guidance, the generic "protein binding" term is uninformative.
      The biologically meaningful BRCA1 interaction (via phospho-Ser990 to the BRCA1
      BRCT domains) is captured in core_functions and in the DSB/HR process
      annotations.
    supported_by:
    - reference_id: PMID:11301010
      supporting_text: BACH1 binds directly to the BRCT repeats of BRCA1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15133502
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation for the BRIP1-BRCA1 BRCT interaction (partner
      BRCA1/P38398; structural/mechanistic study of BRCT recognition of
      phosphorylated BACH1).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative generic MF term; the meaningful BRCA1 phospho-peptide
      interaction is represented in core_functions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17525340
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation (partner BRCA1/P38398) from a study of the
      Abraxas/RAP80-BRCA1 damage-response complex.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein-binding term; BRCA1 association is captured more informatively
      elsewhere.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17581638
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotations (partners BRCA1/P38398 and MLH1/P40692). This
      paper establishes the functionally critical FANCJ-MLH1 (MutLalpha) interaction
      required for the ICL response.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The generic MF term is uninformative, but the underlying MLH1 interaction is
      biologically central and is represented in the interstrand-crosslink-repair
      process annotation and core_functions.
    supported_by:
    - reference_id: PMID:17581638
      supporting_text: FANCJ directly interacts with MLH1 independent of BRCA1, through its helicase domain
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18285836
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation (partner BRCA1/P38398) from a study of the
      pathogenic BRCA1 M1775K BRCT variant that disrupts phosphopeptide binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein-binding term; BRCA1 interaction is captured elsewhere.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19369211
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation (partner BRCA1/P38398) from a study of PALB2 in
      the BRCA complex for HR repair.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative MF term; BRCA1/HR-complex association is represented in the HR
      and DSB-repair process annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21240188
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotations (partners BRCA1/P38398 and BLM/P54132). This
      paper establishes the physical and functional FANCJ-BLM interaction at
      replication-stress foci.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic MF term; the meaningful BLM interaction (co-localization and
      synergistic unwinding under replication stress) is captured in the notes and
      informs the genome-maintenance core function.
    supported_by:
    - reference_id: PMID:21240188
      supporting_text: FANCJ and BLM were found to interact physically and functionally in human cells and co-localize to nuclear foci in response to replication stress
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22792074
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotations (partners BRCA1/P38398 and MLH1/P40692) from a
      study of FANCJ acetylation at Lys-1249 regulating the DNA damage response.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic MF term; BRCA1 and MLH1 interactions are represented more
      informatively elsewhere.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23585563
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotations (partners MLH1/P40692 and MMS19/Q96T76). BRIP1
      interacts with the CIA machinery component MMS19 (and CIAO1/CIAO2B), relevant
      to maturation of its Fe-S cluster.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic MF term; the CIA/MMS19 interaction (Fe-S cluster maturation) is a
      documented, biologically meaningful association noted in the review, but the
      bare "protein binding" term itself is uninformative.
    supported_by:
    - reference_id: PMID:23585563
      supporting_text: MMS19 interacts with target proteins
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25502805
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation (partner MLH1/P40692) from a high-throughput
      variant-cloning/interaction pipeline.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic, high-throughput protein-binding annotation; uninformative as a
      molecular function term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29656893
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation (partner BRCA1/P38398) from a DNA-repair network
      analysis (Shieldin/NHEJ).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein-binding term; not informative as an MF.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation (partner HSD17B14/Q9BPX1) from a systematic
      binary interactome (HuRI). Not an established functional partner.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput binary interaction with no established biological relevance to
      BRIP1 function; the generic MF term is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotations (partners MLH1/P40692 and HSD17B14/Q9BPX1) from
      a proteome-scale interactome (BioPlex).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput protein-binding data; uninformative as a molecular function
      term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34591612
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotations (partners BRCA1/P38398 and MLH1/P40692) from a
      breast-cancer protein interaction landscape.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein-binding term; the BRCA1 and MLH1 interactions are represented
      more informatively elsewhere.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation (partner MLH1/P40692) from a multimodal cell-map
      functional-genomics study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein-binding term; uninformative as an MF.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Immunofluorescence (HPA) localization to the nucleoplasm. Consistent with
      BRIP1 acting on nuclear DNA and forming nucleoplasmic damage foci.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is the primary functional compartment for a soluble
      nuclear DNA repair helicase and is corroborated by nuclear-foci data.
    supported_by:
    - reference_id: PMID:17596542
      supporting_text: FANCJ colocalizes with RPA in nuclear foci after DNA damage
- term:
    id: GO:0031965
    label: nuclear membrane
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Single immunofluorescence (HPA) localization to the nuclear membrane. There is
      no functional evidence for a nuclear-envelope role for this soluble
      nucleoplasmic helicase.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Nuclear-membrane signal is not corroborated by any functional study and is
      likely a peripheral/antibody staining pattern rather than a genuine site of
      BRIP1 action; retained but flagged as an over-annotation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:17596542
  qualifier: located_in
  review:
    summary: >-
      Experimental nuclear localization; FANCJ forms DNA-damage-inducible nuclear
      foci with RPA.
    action: ACCEPT
    reason: >-
      Directly demonstrated nuclear localization and damage-induced focus formation.
    supported_by:
    - reference_id: PMID:17596542
      supporting_text: dependent on the presence of BRCA1, FANCJ colocalizes with RPA in nuclear foci after DNA damage
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: EXP
  original_reference_id: PMID:14983014
  qualifier: enables
  review:
    summary: >-
      Experimental demonstration of intrinsic DNA-dependent ATP hydrolysis by
      purified BRIP1.
    action: ACCEPT
    reason: >-
      Purified recombinant BRIP1 hydrolyzes ATP in a DNA-stimulated manner; the
      catalytic-dead K52R mutant lacks this activity.
    supported_by:
    - reference_id: PMID:14983014
      supporting_text: These results indicate that BACH1 possesses an intrinsic, DNA-dependent ATPase activity
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: EXP
  original_reference_id: PMID:20639400
  qualifier: enables
  review:
    summary: >-
      Experimental ATP hydrolysis activity; the FANCJ-A349P Fe-S-domain mutant
      uncouples ATP hydrolysis from productive unwinding.
    action: ACCEPT
    reason: >-
      Corroborates BRIP1 ATPase activity and its dependence on an intact Fe-S domain
      for coupling to DNA unwinding.
    supported_by:
    - reference_id: PMID:20639400
      supporting_text: defective in coupling adenosine triphosphate (ATP) hydrolysis and translocase activity to unwinding forked duplex or G-quadruplex DNA substrates
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: EXP
  original_reference_id: PMID:36608669
  qualifier: enables
  review:
    summary: >-
      Experimental ATPase activity used by FANCJ to unfold DNA-protein crosslinks at
      replication forks.
    action: ACCEPT
    reason: >-
      FANCJ uses its ATPase activity to unfold protein adducts, directly linking ATP
      hydrolysis to its DPC-repair function.
    supported_by:
    - reference_id: PMID:36608669
      supporting_text: uses its ATPase activity to unfold the protein adduct
- term:
    id: GO:0043139
    label: 5'-3' DNA helicase activity
  evidence_type: EXP
  original_reference_id: PMID:20639400
  qualifier: enables
  review:
    summary: >-
      Experimental 5'-3' helicase activity; unwinding of forked duplex and
      G-quadruplex substrates requires coupling of ATP hydrolysis to translocation.
    action: ACCEPT
    reason: >-
      Core molecular function; the Fe-S-domain A349P mutation abolishes coupled
      unwinding, underscoring that this is the disease-relevant activity.
    supported_by:
    - reference_id: PMID:20639400
      supporting_text: The ability of FANCJ to use the energy from ATP hydrolysis to produce the force required to unwind DNA
- term:
    id: GO:0160225
    label: G-quadruplex unwinding activity
  evidence_type: IDA
  original_reference_id: PMID:18426915
  qualifier: enables
  review:
    summary: >-
      Direct demonstration that FANCJ unwinds G-quadruplex (G4) DNA in an
      ATPase-dependent manner; RPA stimulates and MSH2/MSH6 inhibits this activity.
    action: ACCEPT
    reason: >-
      A well-established, specific molecular function of BRIP1 that underlies its
      role in resolving G4 replication-fork roadblocks and maintaining genome
      stability.
    supported_by:
    - reference_id: PMID:18426915
      supporting_text: FANCJ unwound G4 DNA substrates in an ATPase-dependent manner
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:22369660
  qualifier: located_in
  review:
    summary: >-
      Author-stated nuclear localization (ComplexPortal-assigned) within the BRCA1
      tumor-suppressor network review.
    action: ACCEPT
    reason: >-
      Consistent with abundant experimental evidence for nuclear localization.
    supported_by:
    - reference_id: PMID:17596542
      supporting_text: FANCJ colocalizes with RPA in nuclear foci after DNA damage
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: NAS
  original_reference_id: PMID:22369660
  qualifier: involved_in
  review:
    summary: >-
      Author-stated involvement in DNA repair, from the BRCA1 network review.
      Correct at a general level.
    action: ACCEPT
    reason: >-
      BRIP1 is a core DNA repair factor; general term accurate, with specific
      processes annotated separately.
    supported_by:
    - reference_id: PMID:22369660
      supporting_text: BRCA1 forms at least three mutually exclusive complexes by binding to phosphorylated proteins Abraxas, Bach1 and CTIP
- term:
    id: GO:0035825
    label: homologous recombination
  evidence_type: NAS
  original_reference_id: PMID:22369660
  qualifier: involved_in
  review:
    summary: >-
      Author-stated involvement in homologous recombination, consistent with
      BRIP1's BRCA1-dependent role in HR repair of double-strand breaks.
    action: ACCEPT
    reason: >-
      BRIP1 functions with BRCA1 in homologous recombination repair; supported by
      loss-of-function HR defects.
    supported_by:
    - reference_id: PMID:11301010
      supporting_text: interfered with normal double-strand break repair in a manner that was dependent on its BRCA1 binding function
- term:
    id: GO:0070532
    label: BRCA1-B complex
  evidence_type: IPI
  original_reference_id: PMID:16391231
  qualifier: part_of
  review:
    summary: >-
      BRIP1 is a component of the BRCA1-B (BRCA1-BACH1) complex (ComplexPortal
      CPX-4426), one of the mutually exclusive BRCA1 BRCT-phosphopeptide complexes.
    action: ACCEPT
    reason: >-
      BRIP1/BACH1 defines the "B" complex of BRCA1 via its phospho-Ser990/BRCT
      interaction; membership is well established.
    supported_by:
    - reference_id: PMID:22369660
      supporting_text: BRCA1 forms at least three mutually exclusive complexes by binding to phosphorylated proteins Abraxas, Bach1 and CTIP
- term:
    id: GO:0005657
    label: replication fork
  evidence_type: IDA
  original_reference_id: PMID:36608669
  qualifier: is_active_in
  review:
    summary: >-
      FANCJ acts at the replication fork, where it binds ssDNA downstream of a
      DNA-protein crosslink and unfolds the adduct to enable repair.
    action: ACCEPT
    reason: >-
      Directly localized and functionally characterized at replication forks in DPC
      repair and G4 fork-roadblock resolution.
    supported_by:
    - reference_id: PMID:36608669
      supporting_text: FANCJ binds ssDNA downstream of the DPC and uses its ATPase activity to unfold the protein adduct
- term:
    id: GO:0043139
    label: 5'-3' DNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:36608669
  qualifier: enables
  review:
    summary: >-
      Direct assay of FANCJ 5'-3' helicase activity in the context of DNA-protein
      crosslink unfolding.
    action: ACCEPT
    reason: >-
      Reinforces the core 5'-3' helicase molecular function.
    supported_by:
    - reference_id: PMID:36608669
      supporting_text: we identify a role for the 5'-to-3' helicase FANCJ in DPC repair
- term:
    id: GO:0106300
    label: protein-DNA covalent cross-linking repair
  evidence_type: IDA
  original_reference_id: PMID:36608669
  qualifier: involved_in
  review:
    summary: >-
      FANCJ promotes repair of DNA-protein crosslinks (DPCs): it supports CMG bypass
      and is essential for SPRTN protease activation by unfolding the protein adduct.
    action: ACCEPT
    reason: >-
      A directly demonstrated biological process; FANCJ helicase-mediated protein
      unfolding enables cleavage of the DPC by SPRTN and translesion synthesis past
      non-degradable DPCs.
    supported_by:
    - reference_id: PMID:36608669
      supporting_text: helicase-mediated protein unfolding enables multiple events in DPC repair
- term:
    id: GO:0043139
    label: 5'-3' DNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:14983014
  qualifier: enables
  review:
    summary: >-
      Direct demonstration of 5'-3' DNA helicase activity of purified BRIP1.
    action: ACCEPT
    reason: >-
      The foundational biochemical characterization establishing BRIP1 as a 5'-3'
      DNA helicase.
    supported_by:
    - reference_id: PMID:14983014
      supporting_text: the BACH1 helicase operates as a 5′-to-3′ unwinding protein
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:23585563
  qualifier: located_in
  review:
    summary: >-
      Experimental nuclear localization observed in the study of the CIA (cytosolic
      iron-sulfur assembly) machinery interactions.
    action: ACCEPT
    reason: >-
      Consistent with predominant nuclear localization of BRIP1.
    supported_by:
    - reference_id: PMID:17596542
      supporting_text: FANCJ colocalizes with RPA in nuclear foci after DNA damage
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:23585563
  qualifier: located_in
  review:
    summary: >-
      Experimental cytoplasmic localization associated with the CIA machinery
      (CIAO1/CIAO2B/MMS19) that matures the FANCJ Fe-S cluster.
    action: KEEP_AS_NON_CORE
    reason: >-
      A genuine cytoplasmic pool linked to Fe-S cluster maturation, but not the
      site of BRIP1's core DNA-repair function; retained as non-core.
    supported_by:
    - reference_id: PMID:23585563
      supporting_text: IOP1 functions in the MMS19-dependent CIA pathway
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5684875
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author-statement placing BRIP1 in the nucleoplasm within an
      HR/DSB-response reaction (ATR:ATRIP binding to RPA).
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is correct; this is one of many Reactome pathway
      reactions annotating the same compartment.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5684882
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (CHEK1 recruitment reaction).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5684887
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (CHEK1 activation reaction).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5685011
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (ATR activation reaction).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5685156
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (ATR phosphorylates RPA2).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5685341
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (BCDX2 stabilizes RAD51 filament).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5685838
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (CX3 complex binds D-loops).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5685985
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS nucleoplasm localization; this reaction explicitly involves BRIP1
      recruitment during long-range DSB resection (EXO1/DNA2 with BLM/WRN).
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is correct and this reaction directly references
      BRIP1 recruitment in resection.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5685994
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (long-range resection by EXO1/DNA2).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5686410
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (BLM double-Holliday-junction dissolution).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5686440
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (MUS81:EME1,EME2 cleaves D-loop).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5686469
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (resolution of MUS81-cleaved D-loops).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5686483
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (resolution of Holliday junctions).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5686642
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (RAD52 single-strand annealing).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5686657
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (ERCC1:XPF cleaves SSA flaps).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5686663
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (completion of SSA).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693539
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (ligation/Holliday structure formation).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693542
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (RPA association with resected ssDNA).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693561
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (RAD51 binds BRCA2 at resected DSBs).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693564
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (RAD51 association with RAD52:DSB ends).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693580
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (RAD52 association with RPA complex).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693584
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (Holliday junction cleavage by GEN1/SLX).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693589
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (D-loop dissociation and strand annealing).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693593
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (D-loop extension by DNA polymerases).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693620
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (D-loop formation by PALB2/BRCA2/RAD51).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799332
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (ATR phosphorylates TP53).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9701199
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (defective D-loop formation, BRCA1 LoF).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9704330
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (defective D-loop formation, PALB2 LoF).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9704408
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (defective D-loop formation, PALB2 binding).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9709571
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (BRCA2 RAD51-binding mutants).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9709601
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (defective BRCA2/RAD51 recruitment).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9853389
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (FIGNL1 binds RAD51).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9980006
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (ERCC1:XPF binds SSA intermediates).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9980021
  qualifier: located_in
  review:
    summary: Reactome TAS nucleoplasm localization (LIG1 binds SSA sites).
    action: ACCEPT
    reason: Correct nucleoplasmic compartment for BRIP1.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:14504288
  qualifier: located_in
  review:
    summary: >-
      Nuclear localization annotation sourced from a paper on the UNRELATED bZIP
      transcription factor BACH1 (BTB and CNC homology 1; UniProt O14867), which
      shares the historical "BACH1" alias with BRIP1. Nuclear localization is
      nevertheless correct for BRIP1 from independent evidence.
    action: ACCEPT
    reason: >-
      The term (nucleus) is correct for BRIP1 and abundantly supported by other
      references, so it is retained. However, this specific evidence line is
      mis-attributed: PMID:14504288 studies the transcription factor BACH1
      (heme oxygenase-1 repressor), not the FANCJ helicase; the localization here
      is only coincidentally correct. See reference_review for PMID:14504288.
    supported_by:
    - reference_id: PMID:17596542
      supporting_text: FANCJ colocalizes with RPA in nuclear foci after DNA damage
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:14504288
  qualifier: located_in
  review:
    summary: >-
      Cytoplasmic localization annotation sourced from the UNRELATED transcription
      factor BACH1 paper (PMID:14504288, cadmium-induced nuclear export of the
      HO-1 repressor Bach1). A cytoplasmic pool is independently documented for
      BRIP1 (CIA/Fe-S maturation), so the term is retained as non-core.
    action: KEEP_AS_NON_CORE
    reason: >-
      The cytoplasm term is coincidentally correct for BRIP1 (documented CIA-related
      cytoplasmic pool, PMID:23585563), but the cited evidence (PMID:14504288)
      concerns the bZIP transcription factor BACH1, not FANCJ; the reference is
      mis-attributed via the shared alias. Kept as non-core with the correct
      supporting evidence.
    supported_by:
    - reference_id: PMID:23585563
      supporting_text: IOP1 functions in the MMS19-dependent CIA pathway
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:14504288
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      Annotation of transcriptional-regulation activity mis-mapped to BRIP1 from a
      paper on the UNRELATED bZIP transcription factor BACH1 (BTB and CNC homology
      1; UniProt O14867), a transcriptional repressor of the heme oxygenase-1
      (ho-1) gene. This function belongs to that other BACH1, not to the FANCJ
      helicase.
    action: REMOVE
    reason: >-
      PMID:14504288 ("Cadmium induces nuclear export of Bach1, a transcriptional
      repressor of heme oxygenase-1 gene") is entirely about the bZIP/BTB
      transcription factor BACH1 (Bach1/small Maf heterodimers repressing ho-1,
      competition with Nrf2, Crm1/Exportin-1-dependent nuclear export). It contains
      no data on the BRIP1/FANCJ DNA helicase. BRIP1 is a DNA repair helicase with
      no established sequence-specific transcriptional-regulation function; this
      annotation is a gene-symbol conflation (the "BACH1" alias) and should be
      removed. Verified against the actual publication.
    supported_by:
    - reference_id: PMID:14504288
      supporting_text: ho-1 is repressed by Bach1/small Maf heterodimers, it is activated by Nrf2/small Maf heterodimers
- term:
    id: GO:0000077
    label: DNA damage checkpoint signaling
  evidence_type: NAS
  original_reference_id: PMID:14576433
  qualifier: involved_in
  review:
    summary: >-
      Author-stated involvement in DNA damage checkpoint signaling. BRIP1
      phosphorylation (Ser990) drives its cell-cycle-regulated BRCA1 interaction,
      and FANCJ contributes to the ICL-induced checkpoint/DDR.
    action: KEEP_AS_NON_CORE
    reason: >-
      BRIP1 participates in the DNA damage response (e.g., 4N accumulation control
      after ICLs, acetylation-regulated end processing), so checkpoint involvement
      is plausible and supported, but it is downstream of / secondary to its core
      helicase and repair activities. Retained as non-core.
    supported_by:
    - reference_id: PMID:17581638
      supporting_text: FANCJ helicase activity and MLH1 binding, but not BRCA1 binding, are essential to correct the FA-J cells' ICL-induced 4N DNA accumulation
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: NAS
  original_reference_id: PMID:15878853
  qualifier: enables
  review:
    summary: >-
      Author-stated DNA binding, from the study of BRIP1 DNA substrate specificity
      (preferential binding of forked duplex substrates).
    action: ACCEPT
    reason: >-
      BRIP1 binds DNA as an intrinsic part of its helicase mechanism; directly
      supported by substrate-binding and sequestration assays.
    supported_by:
    - reference_id: PMID:15878853
      supporting_text: BACH1 preferentially binds and unwinds a forked duplex substrate
- term:
    id: GO:0003678
    label: DNA helicase activity
  evidence_type: NAS
  original_reference_id: PMID:11301010
  qualifier: enables
  review:
    summary: >-
      Author-stated DNA helicase activity from the original BACH1 discovery paper
      (a DEAH-family helicase-like protein interacting with BRCA1).
    action: ACCEPT
    reason: >-
      Consistent with subsequently demonstrated biochemical helicase activity of
      BRIP1.
    supported_by:
    - reference_id: PMID:11301010
      supporting_text: BACH1, a member of the DEAH helicase family
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11301010
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation for the direct BRIP1-BRCA1 interaction (partner
      BRCA1/P38398) from the original discovery paper.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic MF term; the biologically central BRCA1 BRCT interaction is captured
      in core_functions and the DSB/HR annotations.
    supported_by:
    - reference_id: PMID:11301010
      supporting_text: BACH1 binds directly to the BRCT repeats of BRCA1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14576433
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation (partner BRCA1/P38398) from the study showing
      BRCA1 BRCT is a phospho-peptide binding domain recognizing phospho-Ser990 of
      BRIP1.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic MF term; the phosphorylation-dependent BRCA1 interaction is
      represented in core_functions.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:11301010
  qualifier: located_in
  review:
    summary: >-
      Author-stated nuclear localization from the original BACH1 discovery paper.
    action: ACCEPT
    reason: >-
      BRIP1 is a nuclear protein; consistent with all experimental localization
      data.
    supported_by:
    - reference_id: PMID:17596542
      supporting_text: FANCJ colocalizes with RPA in nuclear foci after DNA damage
- term:
    id: GO:0006302
    label: double-strand break repair
  evidence_type: NAS
  original_reference_id: PMID:11301010
  qualifier: involved_in
  review:
    summary: >-
      Author-stated involvement in double-strand break repair; a catalytic-dead
      BRIP1 mutant interfered with DSB repair in a BRCA1-binding-dependent manner.
    action: ACCEPT
    reason: >-
      Well supported: BRIP1 is required for efficient DSB repair via its BRCA1
      association, a foundational finding for the gene.
    supported_by:
    - reference_id: PMID:11301010
      supporting_text: interfered with normal double-strand break repair in a manner that was dependent on its BRCA1 binding function
- term:
    id: GO:0036297
    label: interstrand cross-link repair
  evidence_type: IMP
  original_reference_id: PMID:17581638
  qualifier: involved_in
  review:
    summary: >-
      NEW annotation. BRIP1/FANCJ acts late in the Fanconi anemia interstrand
      crosslink (ICL) repair pathway; its helicase activity and MLH1 (MutLalpha)
      binding are required to correct the ICL-induced response of FA-J cells. This
      is arguably BRIP1's most disease-defining biological process yet is absent
      from the existing GOA set.
    action: NEW
    reason: >-
      Strongly supported: FANCJ-null (FA-J) cells accumulate 4N DNA and are
      hypersensitive to ICLs, corrected by wild-type FANCJ in a helicase- and
      MLH1-binding-dependent manner (PMID:17581638); FANCJ deficiency underlies
      Fanconi anemia group J and its cells are hypersensitive to crosslinking agents
      (UniProt DISEASE). Added to capture the ICL-repair process directly.
    supported_by:
    - reference_id: PMID:17581638
      supporting_text: FANCJ helicase activity and MLH1 binding, but not BRCA1 binding, are essential to correct the FA-J cells' ICL-induced 4N DNA accumulation and sensitivity to ICLs
    - reference_id: PMID:18426915
      supporting_text: the FA pathway has been classically described in terms of interstrand cross-link (ICL) repair
- term:
    id: GO:0051539
    label: 4 iron, 4 sulfur cluster binding
  evidence_type: IDA
  original_reference_id: PMID:20639400
  qualifier: enables
  review:
    summary: >-
      NEW annotation. BRIP1 binds a [4Fe-4S] iron-sulfur cluster that is required
      for its helicase activity (Rad3/XPD-family Fe-S helicase). The pathogenic
      A349P substitution adjacent to a conserved Fe-S cysteine reduces bound iron
      and uncouples ATP hydrolysis from DNA unwinding.
    action: NEW
    reason: >-
      Experimentally supported cofactor-binding molecular function (UniProt COFACTOR
      "[4Fe-4S] cluster" with binding residues Cys283/Cys298/Cys310/Cys350; DOMAIN
      "4Fe-4S iron-sulfur-binding is required for helicase activity"). Present in the
      UniProt GO cross-references (as UniProtKB-KW) but missing from the GOA set;
      added because the Fe-S cluster is mechanistically and clinically central.
    supported_by:
    - reference_id: PMID:20639400
      supporting_text: Purified recombinant FANCJ-A349P protein had reduced iron and was defective in coupling adenosine triphosphate (ATP) hydrolysis and translocase activity to unwinding forked duplex or G-quadruplex DNA substrates
core_functions:
- description: >-
    ATP-dependent 5'-to-3' DNA helicase (Fe-S cluster, Rad3/XPD family) that couples
    DNA-dependent ATP hydrolysis to translocation on ssDNA and unwinding of forked
    duplex DNA, acting in BRCA1-dependent homologous recombination repair of DNA
    double-strand breaks and in the Fanconi anemia interstrand-crosslink repair
    pathway.
  molecular_function:
    id: GO:0043139
    label: 5'-3' DNA helicase activity
  directly_involved_in:
  - id: GO:0035825
    label: homologous recombination
  - id: GO:0036297
    label: interstrand cross-link repair
  locations:
  - id: GO:0005654
    label: nucleoplasm
  - id: GO:0005657
    label: replication fork
  in_complex:
    id: GO:0070532
    label: BRCA1-B complex
  supported_by:
  - reference_id: PMID:14983014
    supporting_text: we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase
  - reference_id: PMID:11301010
    supporting_text: interfered with normal double-strand break repair in a manner that was dependent on its BRCA1 binding function
  - reference_id: PMID:17581638
    supporting_text: FANCJ helicase activity and MLH1 binding, but not BRCA1 binding, are essential to correct the FA-J cells' ICL-induced 4N DNA accumulation and sensitivity to ICLs
- description: >-
    G-quadruplex (G4) unwinding activity that resolves four-stranded DNA secondary
    structures which impede replication-fork progression, thereby preventing G4-associated
    genomic instability; stimulated by RPA and inhibited by MSH2/MSH6.
  molecular_function:
    id: GO:0160225
    label: G-quadruplex unwinding activity
  directly_involved_in:
  - id: GO:0006281
    label: DNA repair
  locations:
  - id: GO:0005657
    label: replication fork
  - id: GO:0005654
    label: nucleoplasm
  supported_by:
  - reference_id: PMID:18426915
    supporting_text: FANCJ unwound G4 DNA substrates in an ATPase-dependent manner
  - reference_id: PMID:18426915
    supporting_text: FANCJ preserves genomic stability by directly unwinding DNA roadblocks such as G4 structures that destabilize or impede the replication fork
- description: >-
    Helicase/ATPase-driven unfolding of DNA-protein crosslinks (DPCs) at replication
    forks: FANCJ binds ssDNA downstream of the adduct and uses ATP hydrolysis to unfold
    the crosslinked protein, exposing the DNA for cleavage by the SPRTN protease and
    enabling translesion synthesis past non-degradable DPCs.
  molecular_function:
    id: GO:0043139
    label: 5'-3' DNA helicase activity
  directly_involved_in:
  - id: GO:0106300
    label: protein-DNA covalent cross-linking repair
  locations:
  - id: GO:0005657
    label: replication fork
  supported_by:
  - reference_id: PMID:36608669
    supporting_text: FANCJ binds ssDNA downstream of the DPC and uses its ATPase activity to unfold the protein adduct, which exposes the underlying DNA and enables cleavage of the adduct
  - reference_id: PMID:36608669
    supporting_text: helicase-mediated protein unfolding enables multiple events in DPC repair
proposed_new_terms: []
suggested_questions:
- question: >-
    What is the relative in vivo contribution of BRIP1's BRCA1-dependent HR role
    versus its BRCA1-independent, MLH1-dependent ICL-response role to genome
    stability and tumor suppression?
- question: >-
    Does BRIP1 have a physiological role in meiotic recombination in humans,
    consistent with its testis-enriched expression and the meiotic phenotypes of
    orthologs?
suggested_experiments:
- description: >-
    Separation-of-function analysis in isogenic cells expressing BRIP1 variants that
    selectively disrupt BRCA1 binding, MLH1 binding, Fe-S cluster assembly, or
    catalytic activity, scored for ICL sensitivity, HR efficiency, G4 stability, and
    DPC repair.
  hypothesis: >-
    BRIP1's ICL-repair and HR roles are genetically separable and depend on distinct
    partner interactions rather than solely on helicase catalysis.
- description: >-
    Genome-wide mapping (e.g., CUT&RUN/ChIP) of BRIP1 occupancy at G-quadruplex-forming
    loci and replication-stress sites, correlated with fork progression and mutational
    signatures upon BRIP1 loss.
  hypothesis: >-
    BRIP1 is recruited to G4-forming and stalled-fork loci genome-wide, and its loss
    produces localized instability at these sites.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- 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, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:11301010
  title: BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes
    to its DNA repair function.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Original discovery paper for BRIP1/BACH1/FANCJ. PubMed-verified. Establishes
      the direct BRCA1 BRCT interaction and the BRCA1-dependent role in double-strand
      break repair; abstract explicitly names the DEAH-family helicase-like protein
      BACH1 (=BRIP1), not the transcription factor BACH1.
- id: PMID:14504288
  title: Cadmium induces nuclear export of Bach1, a transcriptional repressor of heme
    oxygenase-1 gene.
  findings: []
  reference_review:
    relevance: NONE
    correctness: WRONG_IDENTIFIER
    review_notes: >-
      This paper concerns the UNRELATED bZIP/BTB transcription factor BACH1 (BTB and
      CNC homology 1; UniProt O14867), a transcriptional repressor of heme
      oxygenase-1, NOT the BRIP1/FANCJ helicase (Q9BX63). The two genes share the
      historical "BACH1" alias. GOA annotations sourced from this PMID
      (nucleus, cytoplasm, and regulation of transcription by RNA polymerase II) are
      mis-mapped; the transcription-regulation annotation was removed and the
      localization annotations retained only because they are independently correct.
- id: PMID:14576433
  title: The BRCT domain is a phospho-protein binding domain.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Shows BRCA1 BRCT recognizes phospho-peptides; maps BRIP1 phospho-Ser990 as the
      BRCA1-interaction determinant. Supports the phosphorylation-dependent BRCA1
      interaction; used here for checkpoint/DDR involvement.
- id: PMID:14983014
  title: The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically
    relevant inactivating mutations.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Foundational biochemistry: purified BRIP1 is a DNA-dependent ATPase and a
      5'-to-3' DNA helicase; breast-cancer variants P47A and M299I are
      helicase-defective. PubMed/PMC full text verified.
- id: PMID:15125843
  title: 'Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide:
    implications for signaling.'
  findings: []
- id: PMID:15133502
  title: Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated
    BACH1 with implications for cancer.
  findings: []
- id: PMID:15878853
  title: Analysis of the DNA substrate specificity of the human BACH1 helicase associated
    with breast cancer.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Defines BRIP1 DNA substrate preferences (forked duplex; minimal 5' ssDNA tail
      of 15 nt; releases D-loop third strand; fails on Holliday junctions). Supports
      DNA binding and the helicase mechanism.
- id: PMID:16391231
  title: Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing
    complexes.
  findings: []
- id: PMID:17525340
  title: Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage
    response.
  findings: []
- id: PMID:17581638
  title: The FANCJ/MutLalpha interaction is required for correction of the cross-link
    response in FA-J cells.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Establishes the BRCA1-independent FANCJ-MLH1 (MutLalpha) interaction required
      for the interstrand-crosslink response; basis for the NEW interstrand
      cross-link repair annotation. PMC full text verified.
- id: PMID:17596542
  title: FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein
    A and interacts physically and functionally with the single-stranded DNA-binding
    protein.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Demonstrates FANCJ-RPA (RPA70) interaction, DNA-damage-inducible nuclear foci
      (BRCA1-dependent), and RPA stimulation of helicase activity. Supports nuclear
      localization and helicase regulation.
- id: PMID:18285836
  title: 'Pathogenicity of the BRCA1 missense variant M1775K is determined by the
    disruption of the BRCT phosphopeptide-binding pocket: a multi-modal approach.'
  findings: []
- id: PMID:18426915
  title: FANCJ helicase defective in Fanconia anemia and breast cancer unwinds G-quadruplex
    DNA to defend genomic stability.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Direct evidence that FANCJ unwinds G-quadruplex DNA in an ATPase-dependent
      manner (RPA-stimulated, MSH2/MSH6-inhibited); source for the G4 unwinding core
      function. PMC full text verified.
- id: PMID:19369211
  title: PALB2 is an integral component of the BRCA complex required for homologous
    recombination repair.
  findings: []
- id: PMID:20639400
  title: Fanconi anemia group J mutation abolishes its DNA repair function by uncoupling
    DNA translocation from helicase activity or disruption of protein-DNA complexes.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Characterizes the FANCJ-A349P Fe-S-domain mutant (reduced iron; uncoupled
      ATP hydrolysis/translocase from unwinding). Source for the 4Fe-4S cluster
      binding NEW annotation and ATPase/helicase annotations. PMC full text verified.
- id: PMID:21240188
  title: Interaction between the helicases genetically linked to Fanconi anemia group
    J and Bloom's syndrome.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Physical/functional FANCJ-BLM interaction and co-localization at
      replication-stress foci; supports genome-maintenance role but the GOA line is a
      generic protein-binding annotation.
- id: PMID:22369660
  title: 'BRCA1 tumor suppressor network: focusing on its tail.'
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Review establishing the BRCA1 A/B/C BRCT-phosphopeptide complexes; BRIP1/Bach1
      defines the "B" complex. Supports nucleus/DNA-repair/HR and BRCA1-B complex
      annotations.
- id: PMID:22792074
  title: FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA damage response.
  findings: []
- id: PMID:23585563
  title: IOP1 protein is an external component of the human cytosolic iron-sulfur
    cluster assembly (CIA) machinery and functions in the MMS19 protein-dependent
    CIA pathway.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Places FANCJ among CIA-machinery target Fe-S proteins (interaction with
      CIAO1/CIAO2B/MMS19); supports cytoplasmic pool and Fe-S cluster maturation.
- id: PMID:25502805
  title: A massively parallel pipeline to clone DNA variants and examine molecular
    phenotypes of human disease mutations.
  findings: []
- id: PMID:26490168
  title: FancJ (Brip1) loss-of-function allele results in spermatogonial cell depletion
    during embryogenesis and altered processing of crossover sites during meiotic
    prophase I in mice.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Mouse Fancj (Brip1) gene-trap study: FANCJ loss alters processing of meiotic
      crossover sites during prophase I (increased MLH1 focus frequency and
      chiasmata, with increased BLM localization). Provides ortholog-level support
      for the IBA meiotic double-strand-break-repair annotation (GO:1990918), which
      previously lacked supporting text. Abstract explicitly identifies FancJ as the
      Fanconi anemia group J DNA helicase (=BRIP1/FANCJ), not the bZIP transcription
      factor BACH1. Cached record is abstract-only.
- id: PMID:29656893
  title: DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and
    PARP Inhibitor Sensitivity.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:34591612
  title: A protein interaction landscape of breast cancer.
  findings: []
- id: PMID:36608669
  title: The FANCJ helicase unfolds DNA-protein crosslinks to promote their repair.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Defines FANCJ's role in DNA-protein-crosslink (DPC) repair: helicase/ATPase
      unfolds the protein adduct to enable SPRTN cleavage and TLS. Source for the DPC
      repair core function, replication-fork localization, and helicase/ATPase
      annotations. PMC full text verified.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: Reactome:R-HSA-5684875
  title: Binding of ATR:ATRIP to RPA at resected DNA DSBs
  findings: []
- id: Reactome:R-HSA-5684882
  title: CHEK1 is recruited to resected DNA DSBs
  findings: []
- id: Reactome:R-HSA-5684887
  title: Activation of CHEK1 at resected DNA DSBs
  findings: []
- id: Reactome:R-HSA-5685011
  title: ATR activation at DNA DSBs
  findings: []
- id: Reactome:R-HSA-5685156
  title: ATR phosphorylates RPA2
  findings: []
- id: Reactome:R-HSA-5685341
  title: BCDX2 complex stabilizes RAD51 filament
  findings: []
- id: Reactome:R-HSA-5685838
  title: CX3 complex binds D-loop structures
  findings: []
- id: Reactome:R-HSA-5685985
  title: EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs
    along with BRIP1 recruitment
  findings: []
- id: Reactome:R-HSA-5685994
  title: Long-range resection of DNA DSBs by EXO1 or DNA2
  findings: []
- id: Reactome:R-HSA-5686410
  title: BLM mediates dissolution of double Holliday junction
  findings: []
- id: Reactome:R-HSA-5686440
  title: MUS81:EME1,EME2 cleaves D-loop
  findings: []
- id: Reactome:R-HSA-5686469
  title: Resolution of D-loops cleaved by MUS81:EME1 or MUS81:EME2
  findings: []
- id: Reactome:R-HSA-5686483
  title: Resolution of Holliday junctions cleaved by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2)
  findings: []
- id: Reactome:R-HSA-5686642
  title: RAD52 promotes single strand annealing at resected DNA DSBs
  findings: []
- id: Reactome:R-HSA-5686657
  title: ERCC1:XPF cleaves flaps generated by SSA
  findings: []
- id: Reactome:R-HSA-5686663
  title: Completion of SSA
  findings: []
- id: Reactome:R-HSA-5693539
  title: Ligation of DNA and formation of Holliday structures following repair synthesis
  findings: []
- id: Reactome:R-HSA-5693542
  title: Association of RPA complexes with ssDNA at resected DNA DSBs
  findings: []
- id: Reactome:R-HSA-5693561
  title: RAD51 binds BRCA2 at resected DNA DSBs
  findings: []
- id: Reactome:R-HSA-5693564
  title: Association of RAD51 with RAD52:DNA double-strand break ends
  findings: []
- id: Reactome:R-HSA-5693580
  title: Association of RAD52 with the RPA complex at resected DNA DSBs
  findings: []
- id: Reactome:R-HSA-5693584
  title: Cleavage of Holliday junctions by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2)
  findings: []
- id: Reactome:R-HSA-5693589
  title: D-loop dissociation and strand annealing
  findings: []
- id: Reactome:R-HSA-5693593
  title: D-loop extension by DNA polymerases
  findings: []
- id: Reactome:R-HSA-5693620
  title: D-loop formation mediated by PALB2, BRCA2 and RAD51
  findings: []
- id: Reactome:R-HSA-6799332
  title: ATR phosphorylates TP53
  findings: []
- id: Reactome:R-HSA-9701199
  title: Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function
    of BRCA1 in PALB2 binding
  findings: []
- id: Reactome:R-HSA-9704330
  title: Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function
    of PALB2 in BRCA1 binding
  findings: []
- id: Reactome:R-HSA-9704408
  title: Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function
    of PALB2 in binding to BRCA2/RAD51/RAD51C
  findings: []
- id: Reactome:R-HSA-9709571
  title: BRCA2 mutants with BRC defects or a defect in the C-terminal RAD51 binding
    site do not bind RAD51
  findings: []
- id: Reactome:R-HSA-9709601
  title: Defective recruitment of BRCA2 and RAD51 due to loss of BRCA2 function in
    PALB2 binding
  findings: []
- id: Reactome:R-HSA-9853389
  title: FIGNL1 binds RAD51
  findings: []
- id: Reactome:R-HSA-9980006
  title: ERCC1:XPF binds DNA DSBs with annealed 3' ssDNA overhangs and displaced flaps
    generated by SSA
  findings: []
- id: Reactome:R-HSA-9980021
  title: LIG1 binds SSA sites
  findings: []