BRIP1 (FANCJ; historically BACH1) is a nuclear iron-sulfur DNA helicase that couples DNA-dependent ATP hydrolysis to 5'-to-3' translocation and strand separation. It unwinds forked duplex DNA and G-quadruplex structures, helping cells traverse DNA replication obstacles and maintain genome stability. BRIP1 binds the BRCT domains of BRCA1 through phosphorylated Ser990 and participates in homologous recombination repair. Its helicase activity and interaction with MLH1 also support the response to DNA interstrand crosslinks through a mechanism separable from BRCA1 binding. At DNA-protein crosslinks, its ATP-driven motor unfolds the protein adduct and exposes adjacent DNA, enabling SPRTN to proteolyze the protein component. RPA and BLM interact with BRIP1 and modulate its genome-maintenance functions. BRIP1 predominantly acts in the nucleoplasm and at stressed replication forks; its iron-sulfur cofactor maturation involves the CIA machinery. Biallelic pathogenic variants cause Fanconi anemia complementation group J, and monoallelic pathogenic variants confer ovarian-cancer susceptibility.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003678 DNA helicase activity | IBA GO_REF:0000033 | ACCEPT | 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. 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. Supporting Evidence: PMID:14983014 we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that BRIP1 is active in the nucleus. Consistent with its role as a nuclear DNA repair/replication helicase. Reason: BRIP1 acts on nuclear DNA in HR, ICL and DPC repair, and forms nuclear DNA-damage foci. Nuclear localization is well supported experimentally. Supporting Evidence: PMID:17596542 FANCJ colocalizes with RPA in nuclear foci after DNA damage |
| GO:0006289 nucleotide-excision repair | IBA GO_REF:0000033 | UNDECIDED | Summary: The IBA traces to a dog-1-supported ancestral assertion, rather than the separate XPD nucleotide-excision-repair node; the supporting worm experiment remains unverified. Reason: The source GOA and cached PAINT IBD agree on PANTHER:PTN000158307 with WB:WBGene00001049 (C. elegans dog-1/O62217). The XPD/P18074 nucleotide-excision-repair assertion is at a different ancestral node, PTN000158239, so the previous XPD-to-FANCJ divergence rationale does not describe this transfer. Official indexed donor records retain experimental IGI and IMP nucleotide-excision-repair annotations, but their linked references and the complete PAINT tree were not recovered in this consultation. A matching FANCJ subfamily assignment corroborates donor identity but does not replace review of the ancestral placement or experiment. The available G/C-tract and interstrand-crosslink studies cannot be assumed to be the exact donor source. Retain uncertainty without inferring an annotation error from donor count, lack of a direct human assay, or the unrelated XPD branch. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000158307 · PTN000158307 UNRESOLVED The cached IBD at this node cites WB:WBGene00001049 (dog-1), and the target IBA uses the same source. The exact experimental donor reference and full ancestral placement remain unverified. This is distinct from the XPD-associated PTN000158239 node. Supporting Evidence: GO_REF:0000033 |
| GO:1990918 double-strand break repair involved in meiotic recombination | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Conserved meiotic DNA-repair involvement is consistent with mouse Fancj crossover phenotypes. Reason: PMID:26490168 explicitly studies a mouse gene-trap allele: the males remained fertile, early synapsis and DSB induction/repair were mostly normal, while MLH1 foci and chiasmata increased. This supports a context-specific role in controlling meiotic recombination rather than general failure of meiotic DSB repair. Retain the curated IBA; testis expression alone is not the evidence, and the complete PAINT topology was not independently reconstructed. Supporting Evidence: GO_REF:0000033 PMID:26490168 indicative of increased DSB repair via CO PMID:26490168 MLH1 focus frequency is increased in Fancj (GT/GT) males |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Nucleic-acid binding is a valid broad description of BRIP1 DNA substrate binding. Reason: The InterPro-derived parent activity is consistent with direct binding to forked DNA and the established helicase mechanism. Its breadth does not make it an excessive biological assertion; the specific DNA-binding and helicase activities are already represented. Supporting Evidence: |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based inference of DNA binding. Correct and relevant — BRIP1 binds and translocates on DNA as part of its helicase mechanism. Reason: DNA binding is experimentally supported (substrate binding/unwinding assays) and is a genuine molecular capability of the enzyme. Supporting Evidence: PMID:15878853 BACH1 preferentially binds and unwinds a forked duplex substrate |
| GO:0003678 DNA helicase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based inference of DNA helicase activity. Correct but generic relative to the experimentally established 5'-3' directionality. Reason: Consistent with the experimentally demonstrated helicase activity of BRIP1. Supporting Evidence: PMID:14983014 we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase |
| GO:0004386 helicase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based inference of generic helicase activity, a parent of DNA helicase activity. Reason: Correct high-level term; the more specific DNA/5'-3' helicase terms are annotated separately with experimental support. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding supports the BRIP1 helicase motor. Reason: UniProt identifies the ATP-binding region, and purified BRIP1 exhibits DNA-stimulated ATP hydrolysis and ATP-dependent unwinding. The K52R catalytic mutant loses these activities in PMID:14983014; the electronic ATP-binding assertion is consistent with the experimentally characterized motor. Supporting Evidence: PMID:14983014 we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location keyword mapping to nucleus. Correct. Reason: Nuclear localization of BRIP1 is well established experimentally. Supporting Evidence: PMID:17596542 FANCJ colocalizes with RPA in nuclear foci after DNA damage |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt maps a secondary cytoplasmic localization for BRIP1. Reason: The immutable UniProt record explicitly cites PMID:23585563 for cytoplasm as well as nucleus. Retain the electronic localization as a secondary compartment while distinguishing it from the predominantly nuclear functional pool. Association with CIA factors alone does not prove a cytoplasmic pool, and the target fractionation image was not independently inspected. Supporting Evidence: |
| GO:0006281 DNA repair | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning electronic annotation of involvement in DNA repair. Correct at a general level. Reason: BRIP1 is a core genome-maintenance/DNA-repair factor; the general term is supported by its experimentally established helicase-dependent DNA repair roles. The precise helicase-controlled step in the interstrand-crosslink response remains an open question. Supporting Evidence: PMID:11301010 contributes to its DNA repair function |
| GO:0016818 hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: The broad phosphoanhydride hydrolase activity is consistent with ATP hydrolysis. Reason: BRIP1 directly hydrolyzes ATP to power its motor. This electronic parent term is less informative than the separately annotated ATP hydrolysis activity, but its generality does not make the assertion false or biologically excessive. Supporting Evidence: |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000116 | ACCEPT | Summary: RHEA/Rhea-mapping electronic annotation of ATP hydrolysis activity. Correct and experimentally corroborated (DNA-dependent ATPase). Reason: BRIP1 is a DNA-dependent ATPase; ATP hydrolysis fuels its translocase/helicase activity. Supporting Evidence: PMID:14983014 we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase |
| GO:0043139 5'-3' DNA helicase activity | IEA GO_REF:0000003 | ACCEPT | 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. Reason: Directly demonstrated: BRIP1 translocates 5'-to-3' and unwinds duplex DNA in an ATP-dependent manner. Supporting Evidence: PMID:14983014 we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase |
| GO:0005515 protein binding | IPI PMID:15125843 Structure of the BRCT repeats of BRCA1 bound to a BACH1 phos... | KEEP AS NON CORE | Summary: BRCA1 recognizes a phosphorylated BRIP1 peptide. Reason: The original abstract directly describes a human BRCA1 BRCT–BACH1 phosphopeptide crystal structure and the Ser990/Phe993 interface. This validates the binding assertion; it does not make generic binding the defining helicase function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15133502 Structure and mechanism of BRCA1 BRCT domain recognition of ... | KEEP AS NON CORE | Summary: A second structure supports phosphorylation-dependent BRIP1–BRCA1 recognition. Reason: The original abstract explicitly reports BRCA1 tandem BRCT domains complexed with the minimal phosphorylated BACH1 interaction region. Retain the physical interaction without inferring that BRIP1 itself is a phosphoprotein-binding receptor. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | KEEP AS NON CORE | Summary: BRIP1 participates in a BRCA1 complex distinct from the Abraxas complex. Reason: The available abstract explicitly distinguishes mutually exclusive BRCA1 binding by Abraxas, BACH1 and CtIP. The source does discuss BACH1 despite its title. This corroborates the established BRCA1 interaction; detailed figures were not inspected. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17581638 The FANCJ/MutLalpha interaction is required for correction o... | KEEP AS NON CORE | Summary: FANCJ binds MLH1 independently of BRCA1 and also forms a BRCA1 complex. Reason: The cached abstract and Discussion explicitly establish direct FANCJ–MLH1 binding and distinguish its requirement in the crosslink response from dispensable BRCA1 binding in that assay. Preserve both GOA partners; do not infer mismatch-repair catalysis or a generic adaptor function from the interaction. Supporting Evidence: PMID:17581638 FANCJ directly interacts with MLH1 independent of BRCA1, through its helicase domain |
| GO:0005515 protein binding | IPI PMID:18285836 Pathogenicity of the BRCA1 missense variant M1775K is determ... | KEEP AS NON CORE | Summary: The BRCA1 M1775K variant impairs recognition of BRIP1. Reason: The available introductory account of this study explicitly reports disruption of the BRCT pocket and inhibition of BRIP1 interaction. This corroborates the independently established interface. The cache does not provide a complete inspected Results/Methods record; do not claim to have inspected its binding figures. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19369211 PALB2 is an integral component of the BRCA complex required ... | KEEP AS NON CORE | Summary: BRIP1 occurs in BRCA1-associated PALB2 complexes. Reason: The cached Discussion specifically reports BACH1 in PALB2 precipitates and distinguishes PALB2 coiled-coil binding from the BRCA1 BRCT complexes. This supports complex association consistent with the established BRIP1–BRCA1 interaction, without proving a new direct BRIP1–PALB2 interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21240188 Interaction between the helicases genetically linked to Fanc... | KEEP AS NON CORE | Summary: BRIP1 physically and functionally interacts with BLM. Reason: The cached abstract and Discussion report reciprocal co-immunoprecipitation from human nuclear extracts and DNA-independent binding of purified FANCJ and BLM. BRCA1 is also a GOA partner and is independently established; the BLM interaction itself does not require BRCA1. Distinguish these partners and retain the supported generic assertion as non-core. Supporting Evidence: PMID:21240188 FANCJ and BLM were found to interact physically and functionally in human cells and co-localize to nuclear foci in response to replication stress |
| GO:0005515 protein binding | IPI PMID:22792074 FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA dam... | KEEP AS NON CORE | Summary: BRIP1 acetylation mutants retain BRCA1 and MLH1 interactions. Reason: Actual Results paragraph37 and Figure4 caption39 describe BRCA1/MLH1 precipitation with WT and K1249R/K1249Q FANCJ and the FA-J-cell assays. Retain the physical association without claiming that acetylation creates or abolishes these interfaces. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23585563 IOP1 protein is an external component of the human cytosolic... | KEEP AS NON CORE | Summary: BRIP1 binds MMS19 and co-precipitates with MLH1. Reason: Actual primary Results for PMID:23585563 describe endogenous FANCJ–MMS19 immunoprecipitation, MLH1 as a known-partner control, and purified FANCJ–MMS19 binding. In the same purified assay CIAO1 did not bind FANCJ. Do not equate larger CIA-complex association with direct binding to every CIA component or annotate BRIP1 as assembling its own iron-sulfur cofactor. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | KEEP AS NON CORE | Summary: Retain the established BRIP1–MLH1 interaction as non-core. Reason: The GOA partner is MLH1. Independent targeted evidence in PMID:17581638 establishes direct FANCJ–MLH1 binding, supporting the generic binding claim under the project policy. The Methods in PMID:25502805 include BRIP1 and MLH1 constructs, but its target-specific variant-screen result was not independently inspected; this judgment does not certify that screen or every tested variant. |
| GO:0005515 protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | KEEP AS NON CORE | Summary: Retain the established BRIP1–BRCA1 interaction as non-core. Reason: The GOA partner is BRCA1. Direct interaction in PMID:11301010 and the BRCA1 BRCT–BRIP1 phosphopeptide structure in PMID:15125843 independently support this binding claim. The target-level assay in the PMID:29656893 repair-network dataset remains uninspected; retaining the established interaction does not claim a separate validation of that dataset. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The reported HSD17B14 interaction remains unresolved. Reason: GOA records the HSD17B14 interaction from the binary interactome. The target-specific assay and controls were not inspected and no physiological role is established here. Neither high throughput nor a generic term alone establishes that the interaction is false or over-annotated. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain generic binding on the established MLH1 association; the HSD17B14 observation remains unresolved. Reason: This GOA row includes MLH1 (P40692) and HSD17B14 (Q9BPX1). Targeted PMID:17581638 evidence independently establishes the MLH1 interaction and supports non-core retention of the generic protein-binding claim. The BioPlex target-level observations and controls were not inspected. This decision does not validate the HSD17B14 edge, establish binary contact for every co-complex association, or assign a physiological role to HSD17B14; the HSD17B14-only source row remains UNDECIDED. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | KEEP AS NON CORE | Summary: Retain the independently established BRCA1 and MLH1 interactions as non-core. Reason: The GOA partners are BRCA1 and MLH1. Direct BRCA1 binding in PMID:11301010 and direct MLH1 binding in PMID:17581638 establish the generic molecular interaction independently of the cancer interaction map. Its target-specific assays remain uninspected, so the decision retains the supported biological claim without certifying the individual map observations. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Retain the independently established MLH1 interaction as non-core. Reason: The GOA partner is MLH1, whose direct interaction with FANCJ is established in PMID:17581638. This supports non-core retention of generic protein binding. The exact assay and target-level evidence in the PMID:40205054 multimodal cell map were not inspected, and this judgment does not imply their independent verification. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence (HPA) localization to the nucleoplasm. Consistent with BRIP1 acting on nuclear DNA and forming nucleoplasmic damage foci. Reason: Nucleoplasmic localization is the primary functional compartment for a soluble nuclear DNA repair helicase and is corroborated by nuclear-foci data. Supporting Evidence: PMID:17596542 FANCJ colocalizes with RPA in nuclear foci after DNA damage |
| GO:0031965 nuclear membrane | IDA GO_REF:0000052 | UNDECIDED | Summary: The HPA nuclear-membrane signal needs target-specific image assessment. Reason: The GO_REF:0000052 IDA record is preserved. Its antibody images, controls and cellular pattern were not inspected, so neither a nuclear-envelope role nor an antibody artifact can be established. The predominant nucleoplasmic function does not contradict an additional nuclear-membrane localization. Supporting Evidence: GO_REF:0000052 |
| GO:0005634 nucleus | EXP PMID:17596542 FANCJ (BACH1) helicase forms DNA damage inducible foci with ... | ACCEPT | Summary: Experimental nuclear localization; FANCJ forms DNA-damage-inducible nuclear foci with RPA. Reason: Directly demonstrated nuclear localization and damage-induced focus formation. Supporting Evidence: PMID:17596542 FANCJ colocalizes with RPA in nuclear foci after DNA damage |
| GO:0016887 ATP hydrolysis activity | EXP PMID:14983014 The BRCA1-associated protein BACH1 is a DNA helicase targete... | ACCEPT | Summary: Experimental demonstration of intrinsic DNA-dependent ATP hydrolysis by purified BRIP1. Reason: Purified recombinant BRIP1 hydrolyzes ATP in a DNA-stimulated manner; the catalytic-dead K52R mutant lacks this activity. Supporting Evidence: PMID:14983014 we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase |
| GO:0016887 ATP hydrolysis activity | EXP PMID:20639400 Fanconi anemia group J mutation abolishes its DNA repair fun... | ACCEPT | Summary: Human BRIP1 ATP hydrolysis can be separated from productive DNA unwinding. Reason: The complete PMID:20639400 abstract and cached Discussion report that purified human A349P retains ATPase and ssDNA translocation while losing duplex/G4 unwinding and protein displacement. This supports the ATPase assertion without claiming that all ATP hydrolysis depends on an intact Fe-S domain. The cache lacks the full Results; separately recovered indexed Results cover purification, iron measurement and selected substrate assays. Supporting Evidence: PMID:20639400 defective in coupling adenosine triphosphate (ATP) hydrolysis and translocase activity to unwinding forked duplex or G-quadruplex DNA substrates |
| GO:0016887 ATP hydrolysis activity | EXP PMID:36608669 The FANCJ helicase unfolds DNA-protein crosslinks to promote... | ACCEPT | Summary: ATP hydrolysis drives BRIP1 motor-dependent protein-adduct unfolding. Reason: PMID:36608669 combines purified human FANCJ with human SPRTN/HMCES substrates and Xenopus extract experiments. ATP-dependent unfolding and proteolysis establish the motor's contribution. Human K52R was aggregation-prone, so the corresponding frog K52R was used in those comparisons; human A349P provides a distinct force-generation control. These constructs should not be conflated. Supporting Evidence: PMID:36608669 uses its ATPase activity to unfold the protein adduct, which exposes the underlying DNA and enables cleavage of the adduct |
| GO:0043139 5'-3' DNA helicase activity | EXP PMID:20639400 Fanconi anemia group J mutation abolishes its DNA repair fun... | ACCEPT | Summary: BRIP1 couples its 5'-to-3' motor to duplex and G4 DNA unwinding. Reason: The original PMID:20639400 abstract and Discussion distinguish WT helicase activity from A349P, which retains ATP hydrolysis/translocation but fails in productive unwinding. The 5'-to-3' polarity is directly established by the two directionality substrates in PMID:14983014. This review does not treat iron quantification as a direct measurement of intact 4Fe-4S stoichiometry. Supporting Evidence: PMID:20639400 defective in coupling adenosine triphosphate (ATP) hydrolysis and translocase activity to unwinding forked duplex or G-quadruplex DNA substrates |
| GO:0160225 G-quadruplex unwinding activity | IDA PMID:18426915 FANCJ helicase defective in Fanconia anemia and breast cance... | ACCEPT | Summary: Direct demonstration that FANCJ unwinds G-quadruplex (G4) DNA in an ATPase-dependent manner; RPA stimulates and MSH2/MSH6 inhibits this activity. Reason: A well-established, specific molecular function of BRIP1 that underlies its role in resolving G4 replication-fork roadblocks and maintaining genome stability. Supporting Evidence: PMID:18426915 FANCJ unwound G4 DNA substrates in an ATPase-dependent manner |
| GO:0005634 nucleus | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | ACCEPT | Summary: Author-stated nuclear localization (ComplexPortal-assigned) within the BRCA1 tumor-suppressor network review. Reason: Consistent with abundant experimental evidence for nuclear localization. Supporting Evidence: PMID:17596542 FANCJ colocalizes with RPA in nuclear foci after DNA damage |
| GO:0006281 DNA repair | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | ACCEPT | Summary: The BRCA1 network review supports BRIP1 participation in DNA repair. Reason: The BRCA1-B sections of PMID:22369660 explicitly discuss BRIP1 ATPase/helicase activity and HR defects after helicase inactivation or depletion. Together with direct enzyme and cellular studies, this supports the existing broad DNA-repair assertion. |
| GO:0035825 homologous recombination | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | ACCEPT | Summary: BRIP1 helicase function and its BRCA1 interaction contribute to homologous recombination. Reason: PMID:22369660 describes the relevant helicase and HR perturbation results in its BRCA1-B section. The original BRIP1 discovery study reports impaired DSB repair from a catalytic-site mutant in a BRCA1-binding-dependent manner. The precise strand-processing step in HR is less settled than BRIP1's contribution; do not infer BRCA2-like RAD51 loading activity. |
| GO:0070532 BRCA1-B complex | IPI PMID:16391231 Multifactorial contributions to an acute DNA damage response... | ACCEPT | Summary: BRIP1 is an established component of the BRCA1-B complex. Reason: The original PMID:16391231 cached Discussion explicitly identifies a BRCA1-BACH1 damage-response complex. PMID:22369660 explains phosphorylation-dependent Ser990 recognition by BRCA1 BRCT. The original cache provides Abstract/Discussion, not a complete inspected Results section; complex membership is also supported by the targeted BRCA1-binding studies. |
| GO:0005657 replication fork | IDA PMID:36608669 The FANCJ helicase unfolds DNA-protein crosslinks to promote... | ACCEPT | Summary: BRIP1 acts at replication forks encountering DNA-protein crosslinks. Reason: PMID:36608669 examines replication-coupled DPC repair in Xenopus egg extracts and reconstitutes human FANCJ-dependent unfolding/proteolysis. The cached human GO-CAM independently places its helicase activity at the replication fork. This is a supported functional fork location; it is not a claim that every in-vitro assay directly images human fork recruitment or assays G4 unwinding. Supporting Evidence: PMID:36608669 uses its ATPase activity to unfold the protein adduct, which exposes the underlying DNA and enables cleavage of the adduct |
| GO:0043139 5'-3' DNA helicase activity | IDA PMID:36608669 The FANCJ helicase unfolds DNA-protein crosslinks to promote... | ACCEPT | Summary: The BRIP1 5'-to-3' helicase motor supports DNA-protein-crosslink repair. Reason: The source assays motor-dependent remodeling and distinguishes helicase-defective variants, while its introductory polarity statement is not itself a new directionality experiment. Direct polarity assays are available in PMID:14983014. The curated GO-CAM associates the same helicase activity with BRIP1-mediated DPC repair, without assigning SPRTN protease activity to BRIP1. |
| GO:0106300 protein-DNA covalent cross-linking repair | IDA PMID:36608669 The FANCJ helicase unfolds DNA-protein crosslinks to promote... | ACCEPT | Summary: BRIP1 actively unfolds a covalent protein adduct to promote DPC repair. Reason: Purified human FANCJ promotes unfolding of the HMCES protein adduct and enables human SPRTN to cleave that protein. Xenopus extract experiments also examine CMG bypass and replication-coupled repair. FANCJ is a backup to RTEL1 for some CMG-bypass events, and the TLS reconstitution distinguishes human Pol-eta approach from yeast Pol-zeta/Rev1 bypass. Do not claim DNA cleavage by a protease, universal dependence of SPRTN function, or unrestricted stimulation of every TLS polymerase. Supporting Evidence: PMID:36608669 uses its ATPase activity to unfold the protein adduct, which exposes the underlying DNA and enables cleavage of the adduct |
| GO:0043139 5'-3' DNA helicase activity | IDA PMID:14983014 The BRCA1-associated protein BACH1 is a DNA helicase targete... | ACCEPT | Summary: Direct demonstration of 5'-3' DNA helicase activity of purified BRIP1. Reason: The foundational biochemical characterization establishing BRIP1 as a 5'-3' DNA helicase. Supporting Evidence: PMID:14983014 we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase |
| GO:0005634 nucleus | IDA PMID:23585563 IOP1 protein is an external component of the human cytosolic... | ACCEPT | Summary: FANCJ is predominantly nuclear in the CIA-machinery study. Reason: Actual recovered PMID:23585563 Results and the Figure2 caption describe predominantly nuclear FANCJ in WT and MMS19-depleted HeLa cells. The image itself was not accessible for independent visual inspection. This corroborates the independently reported DNA-damage-induced nuclear foci in PMID:17596542. Supporting Evidence: PMID:17596542 FANCJ colocalizes with RPA in nuclear foci after DNA damage |
| GO:0005737 cytoplasm | IDA PMID:23585563 IOP1 protein is an external component of the human cytosolic... | KEEP AS NON CORE | Summary: Retain the curated secondary cytoplasmic localization. Reason: UniProt explicitly cites PMID:23585563 for cytoplasm as well as nucleus. Defer to the experimental curator for this secondary compartment, consistently with the electronic mapping. The recovered Results emphasize the nuclear pool; the Figure 2 fractionation image was not independently inspected, so no claim is made about cytoplasmic abundance or activity. The IOP1 pathway statement concerns a different protein and is not used as a FANCJ localization anchor. Supporting Evidence: |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684875 | ACCEPT | Summary: Reactome traceable-author-statement placing BRIP1 in the nucleoplasm within an HR/DSB-response reaction (ATR:ATRIP binding to RPA). Reason: Nucleoplasmic localization is correct; this is one of many Reactome pathway reactions annotating the same compartment. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684882 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (CHEK1 recruitment reaction). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684887 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (CHEK1 activation reaction). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685011 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (ATR activation reaction). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685156 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (ATR phosphorylates RPA2). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685341 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (BCDX2 stabilizes RAD51 filament). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685838 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (CX3 complex binds D-loops). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685985 | ACCEPT | Summary: Reactome TAS nucleoplasm localization; this reaction explicitly involves BRIP1 recruitment during long-range DSB resection (EXO1/DNA2 with BLM/WRN). Reason: Nucleoplasmic localization is correct and this reaction directly references BRIP1 recruitment in resection. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685994 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (long-range resection by EXO1/DNA2). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686410 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (BLM double-Holliday-junction dissolution). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686440 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (MUS81:EME1,EME2 cleaves D-loop). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686469 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (resolution of MUS81-cleaved D-loops). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686483 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (resolution of Holliday junctions). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686642 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (RAD52 single-strand annealing). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686657 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (ERCC1:XPF cleaves SSA flaps). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686663 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (completion of SSA). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693539 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (ligation/Holliday structure formation). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693542 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (RPA association with resected ssDNA). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693561 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (RAD51 binds BRCA2 at resected DSBs). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693564 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (RAD51 association with RAD52:DSB ends). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693580 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (RAD52 association with RPA complex). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693584 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (Holliday junction cleavage by GEN1/SLX). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693589 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (D-loop dissociation and strand annealing). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693593 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (D-loop extension by DNA polymerases). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693620 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (D-loop formation by PALB2/BRCA2/RAD51). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6799332 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (ATR phosphorylates TP53). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701199 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (defective D-loop formation, BRCA1 LoF). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704330 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (defective D-loop formation, PALB2 LoF). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704408 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (defective D-loop formation, PALB2 binding). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709571 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (BRCA2 RAD51-binding mutants). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709601 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (defective BRCA2/RAD51 recruitment). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9853389 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (FIGNL1 binds RAD51). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9980006 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (ERCC1:XPF binds SSA intermediates). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9980021 | ACCEPT | Summary: Reactome TAS nucleoplasm localization (LIG1 binds SSA sites). Reason: Correct nucleoplasmic compartment for BRIP1. This row asserts the nucleoplasmic compartment, not that BRIP1 catalyzes the named reaction. Nuclear-foci evidence and the curated repair context support the localization. |
| GO:0005634 nucleus | IDA PMID:14504288 Cadmium induces nuclear export of Bach1, a transcriptional r... | ACCEPT | Summary: Nuclear localization is independently established, although the original assay uses transcription-factor Bach1. Reason: The retrieved PMID:14504288 Methods/Results and captions describe FLAG Bach1 BTB/CLS/bZIP constructs, small Maf and an HO-1 reporter in mammalian cell systems. These positively identify the transcription factor rather than FANCJ; this is stronger evidence than a title-based alias objection. The complete paper was not read. Retain the biologically correct nuclear term using the independent FANCJ nuclear-foci study, and record the citation problem explicitly. Supporting Evidence: PMID:17596542 FANCJ colocalizes with RPA in nuclear foci after DNA damage |
| GO:0005737 cytoplasm | IDA PMID:14504288 Cadmium induces nuclear export of Bach1, a transcriptional r... | KEEP AS NON CORE | Summary: Retain secondary cytoplasmic localization on independent evidence, while flagging the original citation mismatch. Reason: The inspected PMID:14504288 constructs and HO-1/Maf assays concern the separate BTB/bZIP transcription factor BACH1, so that paper is not positive evidence for FANCJ localization. The generic localization claim is retained on independent UniProt curation citing PMID:23585563, with the same curator deference and uninspected fractionation-image limit as the matching IDA row. Preserve original_reference_id for source provenance and the MISCITED reference assessment; do not claim a verified FANCJ export assay. Supporting Evidence: |
| GO:0006357 regulation of transcription by RNA polymerase II | IDA PMID:14504288 Cadmium induces nuclear export of Bach1, a transcriptional r... | REMOVE | Summary: The inspected transcription-regulation experiments concern the distinct BTB/bZIP Bach1 protein. Reason: Actual publisher-indexed Methods/Results and Figure1-10 captions describe FLAG Bach1 BTB/CLS/leucine-zipper constructs, MafK and HO-1 transcriptional reporters in 293/293T and GM02063 cells. These assay entities identify transcription-factor BACH1, not the BRIP1 helicase. GO:0006357 broadly covers modulation of RNA-polymerase-II transcription and does not require sequence-specific DNA binding; the reason for removal is the positively identified source protein, not an assumed absence of transcription-related biology in BRIP1. The full paper was not completely accessed, so the former global claim that it contains no BRIP1 data is withdrawn. Supporting Evidence: PMID:14504288 ho-1 is repressed by Bach1/small Maf heterodimers, it is activated by Nrf2/small Maf heterodimers |
| GO:0000077 DNA damage checkpoint signaling | NAS PMID:14576433 The BRCT domain is a phospho-protein binding domain. | KEEP AS NON CORE | Summary: The phosphorylation-dependent BRIP1-BRCA1 interaction contributes to a DNA-damage checkpoint. Reason: The original PMID:14576433 abstract explicitly links this regulated interaction to DNA-damage-induced G2-to-M checkpoint control. PMID:22369660 distinguishes G2 accumulation and replication-stress checkpoints from the transient G2/M checkpoint. Retain a supported broader response context without assigning BRIP1 an intrinsic sensor or checkpoint-kinase activity. |
| GO:0003677 DNA binding | NAS PMID:15878853 Analysis of the DNA substrate specificity of the human BACH1... | ACCEPT | Summary: Author-stated DNA binding, from the study of BRIP1 DNA substrate specificity (preferential binding of forked duplex substrates). Reason: BRIP1 binds DNA as an intrinsic part of its helicase mechanism; directly supported by substrate-binding and sequestration assays. Supporting Evidence: PMID:15878853 BACH1 preferentially binds and unwinds a forked duplex substrate |
| GO:0003678 DNA helicase activity | NAS PMID:11301010 BACH1, a novel helicase-like protein, interacts directly wit... | ACCEPT | Summary: The discovery annotation is consistent with subsequently demonstrated DNA helicase activity. Reason: PMID:11301010 identified the BRCA1-binding helicase-family protein; the direct ATP-dependent strand-separation and polarity assays in PMID:14983014 establish the activity. The discovery abstract alone did not constitute the later purified-enzyme assay. |
| GO:0005515 protein binding | IPI PMID:11301010 BACH1, a novel helicase-like protein, interacts directly wit... | KEEP AS NON CORE | Summary: BRIP1 directly binds the BRCT repeats of BRCA1. Reason: The original discovery abstract explicitly establishes direct binding and a BRCA1-binding-dependent DNA-repair phenotype. This is a real molecular association, retained without elevating generic binding above BRIP1 helicase activity. Supporting Evidence: PMID:11301010 BACH1 binds directly to the BRCT repeats of BRCA1 |
| GO:0005515 protein binding | IPI PMID:14576433 The BRCT domain is a phospho-protein binding domain. | KEEP AS NON CORE | Summary: BRCA1 binds phosphorylated BRIP1 in a regulated interaction. Reason: The original abstract directly identifies phosphorylated BACH1 as the BRCA1 BRCT ligand and relates the interaction to cell-cycle checkpoint control. Retain the interaction while avoiding reversal of ligand and receptor roles. Supporting Evidence: |
| GO:0005634 nucleus | NAS PMID:11301010 BACH1, a novel helicase-like protein, interacts directly wit... | ACCEPT | Summary: Author-stated nuclear localization from the original BACH1 discovery paper. Reason: The discovery annotation is corroborated by the explicit nuclear-foci experiments summarized in PMID:17596542; a secondary cytoplasmic pool does not invalidate nuclear localization. Supporting Evidence: PMID:17596542 FANCJ colocalizes with RPA in nuclear foci after DNA damage |
| GO:0006302 double-strand break repair | NAS PMID:11301010 BACH1, a novel helicase-like protein, interacts directly wit... | ACCEPT | Summary: Author-stated involvement in double-strand break repair; a catalytic-dead BRIP1 mutant interfered with DSB repair in a BRCA1-binding-dependent manner. Reason: Well supported: BRIP1 is required for efficient DSB repair via its BRCA1 association, a foundational finding for the gene. Supporting Evidence: PMID:11301010 interfered with normal double-strand break repair |
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Download this section (compressed HTML)Q: 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?
Q: Does BRIP1 have a physiological role in meiotic recombination in humans, consistent with its testis-enriched expression and the meiotic phenotypes of orthologs?
Q: Which exact dog-1 experimental evidence and PAINT ancestral placement support the BRIP1 nucleotide-excision-repair IBA at PTN000158307?
Q: Does validated FANCJ imaging substantiate the HPA nuclear-membrane annotation and the small cytoplasmic pool reported by UniProt?
Q: Which BRIP1-controlled molecular step connects its MLH1 interaction and helicase motor to interstrand-crosslink repair, distinct from checkpoint recovery?
Q: What directly measured cluster composition and occupancy establish the intact human BRIP1 iron-sulfur cofactor under functional assay conditions?
Experiment: 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.
Experiment: 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.
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