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FLASH GENE
Symbol BRIP1 contributors: mct - updated : 02-02-2014
HGNC name BRCA1 interacting protein C-terminal helicase 1
HGNC id 20473
Corresponding disease
FANCJ Fanconi anemia, complementation groupe J
Location 17q23.2      Physical location : 59.756.548 - 59.940.920
Synonym name
  • BRCA1-interacting protein 1
  • BRCA1-associated C terminal helicase 1
  • Fanconi anemia group J protein
  • protein FACJ
  • ATP-dependent RNA helicase BRIP1
  • Synonym symbol(s) BACH1, OF, FLJ90232, MGC126521, MGC126523, FANCJ
    EC.number 3.6.4.13
    DNA
    TYPE functioning gene
    STRUCTURE 184.37 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure four novel variations in the promoter region of FANCJ, one of these significantly altering the promoter activity in breast cancer families
    MAPPING cloned Y linked N status provisional
    Physical map
    TUBD1 17q23.2 likely ortholog of mouse tubulin, delta 1 RPS6KB1 17q23.3 ribosomal protein S6 kinase, 70kDa, polypeptide 1 LOC51136 17q23.2 PTD016 protein LOC390805 17 similar to DEAH (Asp-Glu-Ala-His) box polypeptide 40 LOC388404 17 similar to TBC1 domain family member 3 (Rab GTPase-activating protein PRC17) (Prostate cancer gene 17 protein) (TRE17 alpha protein) LOC201201 17q23.2 hypothetical LOC201201 ABC1 17q23.2-q23.3 amplified in breast cancer 1 LOC388405 17 LOC388405 CA4 17q23 carbonic anhydrase IV USP32 17q23.3 ubiquitin specific protease 32 LOC124773 17q23.3 hypothetical protein LOC124773 LOC284166 17q23.3 similar to 60S ribosomal protein L12 APPBP2 17q23 amyloid beta precursor protein (cytoplasmic tail) binding protein 2 LOC388406 17 hypothetical gene supported by AK131012 PPM1D 17q23.1 protein phosphatase 1D magnesium-dependent, delta isoform BCAS3 17q23 breast carcinoma amplified sequence 3 TBX2 17q23 T-box 2 LOC388407 17 hypothetical gene supported by BC046200 TBX4 17q23 T-box 4 MGC71999 17q23.3 alpha-NAC protein BRIP1 17q22-q24 BRCA1 interacting protein C-terminal helicase 1 KIAA1287 17q23.3 KIAA1287 protein TRAP240 17q23 KIAA1287 protein LOC284167 17q23.3 similar to RPOM_HUMAN LOC388408 17 similar to Ribosomal protein S6 kinase (S6K) (p70-S6K) LOC388409 17 hypothetical gene supported by BC058890 FLJ25818 17q24.1 hypothetical protein FLJ25818 FLJ12760 17q24.1 hypothetical protein FLJ12760 TLK2 17q23 tousled-like kinase 2 MRC2 17q21.1-q23 mannose receptor, C type 2 FLJ35757 17q24.1 hypothetical protein FLJ35757 DKFZP564D166 17q24.1 putative ankyrin-repeat containing protein CYB561 17q11-qter cytochrome b-561
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 - 8166 - 1249 - 2001 11595410
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node    
    Reproductivefemale systembreastmammary gland highly
     male systemtestis  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven helicase specific motifs
  • a nuclear localization signal (NLS)
  • a Q motif DEAH box DNA helicase implicated in Fanconi anemia and breast cancer, regulating its dimerization, DNA binding, and DNA repair function
  • C-terminal part interact with BRCA1 via its BRCA1 C-terminal (BRCT) repeats
  • HOMOLOGY
    interspecies ortholog to rattus Brip1_predicted
    ortholog to murine Brip1
    Homologene
    FAMILY
  • RecQ-DEAH helicase family
  • DEAD box helicase family
  • DEAH subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    intracellular,nuclear envelope
    text colocalizes with RPA1 in nuclear foci after DNA damage
    basic FUNCTION
  • plays an important role in the maintenance of genome integrity
  • having functions in the replicational stress response, and involved in the resolution of alternate DNA structures that impede replication
  • helicase interacting directly with the BRCT domain of BRCA1 and contributing to its DNA repair function
  • essential tumor suppressor, required for DNA damage-induced checkpoint control during the transition from G2 to M phase of the cell cycle
  • having a function in the Fanconi anemia pathway that is independent of BRCA1 and downstream of FANCD2 activation
  • BRCA1-associated DNA helicase that contributes to homologous recombination and cross-link repair
  • having a role in the maintenance of potentially unstable genomic G/C tracts during replication
  • may play a role in a homologous recombination pathway of double strand break repair
  • roles of RPA1, BRIP1, and other DNA helicases in the metabolism of damaged DNA that can interfere with basic cellular processes of DNA metabolism
  • can inhibit RAD51 strand exchange, an activity that is likely to be important for its role in controlling DNA repair through homologous recombination
  • likely may perform its catalytic functions in DNA repair and stabilization of the replication fork by displacing DNA-bound proteins or unwinding alternate DNA structures that interfere with normal DNA transactions and lead to genomic instability
  • senses oxidative base damage in either strand of duplex DNA and unwinds the damaged DNA substrate in a strand-specific manner
  • with TOPBP1, are required for ATR-dependent phosphorylation events in response to replication stress
  • when unable to bind BRCA1, promotes poleta-dependent bypass
  • helicase that has been implicated in the maintenance of genomic stability
  • BRIP1 catalytic activity and its effect on BLM protein stability contribute to preservation of genomic stability and a normal response to replication stress
  • stimulates homologous recombination, which depends on the integrity of the helicase domain
  • BRIP1 acetylation facilitates DNA end processing required for repair and checkpoint signaling
  • CELLULAR PROCESS nucleotide, repair
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • member of the group III Fanconi anemia proteins, with FANCN (PALB2), and BRCA1, which do not play a role in FANCD2 monoubiquitination
  • INTERACTION
    DNA binding
    RNA
    small molecule cofactor,
  • ATP
  • protein
  • partner of BRCA1 (BRCT repeat domain) contributing to repair function of BRCA1
  • interacts with the mismatch repair complex MutL, composed of PMS2 and MLH1 (predicts a broader role for FANCJ in DNA damage signaling independent of BRCA1)
  • BRIP1-RPA1 interaction is likely to be important for the role of the helicase to more efficiently unwind DNA repair intermediates to maintain genomic stability
  • TOPBP1/BRIP1 interaction is mediated by the very C-terminal tandem BRCT domains of TOPBP1 and S phase-specific phosphorylation of BRIP1 at Thr 1133 site
  • recruited in response to replication stress and BRIP1 may serve to link FANCD2 to BRCA1
  • TOPBP1 binds BRIP1, one of its critical partners in the DNA damage response (crucial for the response to DNA replication stress)
  • BLM and and BRIP1 were found to interact physically and functionally in human cells
  • interacts with BRCA1 and MLH1 (mutL homologue 1), which differentially control DNA DSB (double-strand break) repair processes
  • RAS regulates BRIP1 expression to induce dissociation of BRCA1 from chromatin, inhibit DNA repair, and promote senescence
  • BRIP1 was able to displace TERF2 from the telomeric substrate in an RPA1-dependent manner
  • not only FANCD2 regulates BRIP1 chromatin localization but also BRIP1 is necessary for efficient loading of FANCD2 onto chromatin following DNA damage caused by mitomycin C treatment
  • BRCA1 and BRIP1 cooperatively promote interstrand crosslinker induced centrosome amplification through the activation of PLK1
  • FANCD2, BRIP1 and BRCA2 cooperate to promote replication fork recovery independently of the Fanconi Anemia core complex
  • cell & other
    REGULATION
    activated by after IRF1 over-expression (Frontini 2009)
    Other dynamic regulation of BRIP1 acetylation is critical for robust DNA damage response, recombination-based processing, and ultimately checkpoint maintenance
    ASSOCIATED DISORDERS
    corresponding disease(s) FANCJ
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in breast carcinoma (sporadic or not)
    tumoral germinal mutation      
    affecting the helicase domain activity identified in early onset breast cancer
    constitutional       loss of function
    BRIP1-deficient cells display increased sister chromatid exchange and sensitivity to replication stress
    tumoral germinal mutation     loss of function
    in patients with primary ovarian, fallopian tube, or peritoneal cancers
    Susceptibility
  • moderate-risk alleles for breast cancer
  • to ovarian cancer
  • Variant & Polymorphism SNP
  • c.2040_2041insTT, in the BRIP1 (FANCJ) gene confers an increase in ovarian cancer risk
  • Candidate gene
  • unregulated function of BRIP1 could be associated with cancer and/or chemoresistance
  • Marker
    Therapy target
    ANIMAL & CELL MODELS