BRIP1 (original) (raw)

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Mammalian protein found in Homo sapiens

BRIP1
Available structuresPDBOrtholog search: PDBe RCSB List of PDB id codes1T15, 1T29, 3AL3
Identifiers
Aliases BRIP1, BACH1, FANCJ, OF, BRCA1 interacting protein C-terminal helicase 1, BRCA1 interacting helicase 1
External IDs OMIM: 605882; MGI: 2442836; HomoloGene: 32766; GeneCards: BRIP1; OMA:BRIP1 - orthologs
Gene location (Human)Chromosome 17 (human)Chr.Chromosome 17 (human)[1]Chromosome 17 (human)Genomic location for BRIP1Genomic location for BRIP1Band17q23.2Start61,679,139 bp[1]End61,863,559 bp[1]
Gene location (Mouse)Chromosome 11 (mouse)Chr.Chromosome 11 (mouse)[2]Chromosome 11 (mouse)Genomic location for BRIP1Genomic location for BRIP1Band11|11 CStart85,948,964 bp[2]End86,092,019 bp[2]
RNA expression patternBgeeHuman Mouse (ortholog)Top expressed inventricular zonegonadtesticlesecondary oocyteganglionic eminencestromal cell of endometriumbone marrowbone marrow cellstrabecular boneleft testisTop expressed inzygoteprimary oocytegenital tubercletail of embryosecondary oocyteyolk sacmorulagray matter layer of cerebellumventricular zonespermatidMore reference expression dataBioGPSMore reference expression data
Gene ontologyMolecular function DNA binding 4 iron, 4 sulfur cluster binding nucleotide binding helicase activity iron-sulfur cluster binding DNA helicase activity metal ion binding hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides protein binding nucleic acid binding hydrolase activity ATP binding chromatin binding Cellular component cytoplasm nuclear membrane nucleoplasm nucleus Biological process regulation of transcription by RNA polymerase II DNA damage checkpoint signaling cellular response to DNA damage stimulus cellular response to vitamin nucleobase-containing compound metabolic process negative regulation of cell population proliferation DNA replication DNA duplex unwinding double-strand break repair DNA repair homologous chromosome pairing at meiosis spermatogenesis spermatogonial cell division spermatid development male gonad development response to toxic substance negative regulation of gene expression meiotic DNA double-strand break processing involved in reciprocal meiotic recombination chiasma assembly cellular response to hypoxia seminiferous tubule development cellular response to angiotensin double-strand break repair involved in meiotic recombination nucleotide-excision repair regulation of signal transduction by p53 class mediator Sources:Amigo / QuickGO
OrthologsSpeciesHuman MouseEntrez83990237911EnsemblENSG00000136492ENSMUSG00000034329UniProtQ9BX63Q5SXJ3RefSeq (mRNA)NM_032043NM_178309RefSeq (protein)NP_114432NP_840094Location (UCSC)Chr 17: 61.68 – 61.86 MbChr 11: 85.95 – 86.09 MbPubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Fanconi anemia group J protein is a protein that in humans is encoded by the BRCA1-interacting protein 1 (BRIP1) gene.[5][6][7]

The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations.[7]

This protein also appears to be important in ovarian cancer where it seems to act as a tumor suppressor.[8] Mutations in BRIP1 are associated with a 10-15% risk of ovarian cancer.[9]

BRIP1 appears to have an important role in neuronal cells by suppressing oxidative stress, excitotoxicity induced DNA damage, and in protecting the integrity of mitochondria.[10] A deficiency of BRIP1 causes increased DNA damage, mitochondrial abnormalities and neuronal cell death.

BRIP1 protein is a DNA helicase that is employed in homologous recombinational repair, and in the response of the cell to DNA replication stress.[11] In part, BRIP1 carries out its function through interaction with other key DNA repair proteins, specifically MLH1, BRCA1 and BLM.[11] This group of proteins helps to ensuring genome stability, and in particular repairs DNA double-strand breaks during prophase 1 of meiosis.

During prophase I of meiosis in male mice, BRIP1 functions in the repair of DNA double-strand breaks, but does not appear to have a role in the formation of chromosomal crossovers.[12] BRIP1 co-localizes with TOPBP1 scaffold protein and the BRCA1 repair protein along chromosome cores starting early in meiotic prophase I forming discrete foci, and is also densely localized to the axes of unsynapsed chromosomes during the late zygonema (zygotene) stage of meiosis.[12]

BRIP1 has been shown to interact with BRCA1.[13][14][15][16][17]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000136492 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034329 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Menichini P, Linial M (November 2001). "SUVi and BACH1: a new subfamily of mammalian helicases?". Mutation Research. 487 (1–2): 67–71. doi:10.1016/s0921-8777(01)00104-5. PMID 11595410.
  6. ^ Cantor SB, Bell DW, Ganesan S, Kass EM, Drapkin R, Grossman S, et al. (April 2001). "BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function". Cell. 105 (1): 149–160. doi:10.1016/S0092-8674(01)00304-X. PMID 11301010. S2CID 15966253.
  7. ^ a b "Entrez Gene: BRIP1 BRCA1 interacting protein C-terminal helicase 1".
  8. ^ Rafnar T, Gudbjartsson DF, Sulem P, Jonasdottir A, Sigurdsson A, Jonasdottir A, et al. (October 2011). "Mutations in BRIP1 confer high risk of ovarian cancer". Nature Genetics. 43 (11): 1104–1107. doi:10.1038/ng.955. hdl:2336/228034. PMID 21964575. S2CID 24535565.
  9. ^ Ring KL, Garcia C, Thomas MH, Modesitt SC (November 2017). "Current and future role of genetic screening in gynecologic malignancies". American Journal of Obstetrics and Gynecology. 217 (5): 512–521. doi:10.1016/j.ajog.2017.04.011. PMID 28411145. S2CID 29024566.
  10. ^ Mani C, Acharya G, Kshirsagar S, Vijayan M, Khan H, Reddy PH, Palle K (2022). "A Novel Role for BRIP1/FANCJ in Neuronal Cells Health and in Resolving Oxidative Stress-Induced DNA Lesions". Journal of Alzheimer's Disease. 85 (1): 207–221. doi:10.3233/JAD-215305. PMID 34776453. S2CID 244078679.
  11. ^ a b Sun X, Brieño-Enríquez MA, Cornelius A, Modzelewski AJ, Maley TT, Campbell-Peterson KM, et al. (June 2016). "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". Chromosoma. 125 (2): 237–252. doi:10.1007/s00412-015-0549-2. PMC 5415080. PMID 26490168.
  12. ^ a b Horan TS, Ascenção CF, Mellor CA, Wang M, Smolka MB, Cohen PE (October 2023). "The DNA helicase FANCJ (BRIP1) functions in Double Strand Break repair processing, but not crossover formation during Prophase I of meiosis in male mice". bioRxiv. doi:10.1101/2023.10.06.561296. PMC 10592954. PMID 37873301.
  13. ^ Botuyan MV, Nominé Y, Yu X, Juranic N, Macura S, Chen J, Mer G (July 2004). "Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains". Structure. 12 (7): 1137–1146. doi:10.1016/j.str.2004.06.002. PMC 3652423. PMID 15242590.
  14. ^ Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP (March 2002). "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development. 16 (5): 583–593. doi:10.1101/gad.959202. PMC 155350. PMID 11877378.
  15. ^ Yu X, Chini CC, He M, Mer G, Chen J (October 2003). "The BRCT domain is a phospho-protein binding domain". Science. 302 (5645): 639–642. Bibcode:2003Sci...302..639Y. doi:10.1126/science.1088753. PMID 14576433. S2CID 29407635.
  16. ^ Rodriguez M, Yu X, Chen J, Songyang Z (December 2003). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". The Journal of Biological Chemistry. 278 (52): 52914–52918. doi:10.1074/jbc.C300407200. PMID 14578343.
  17. ^ Clapperton JA, Manke IA, Lowery DM, Ho T, Haire LF, Yaffe MB, Smerdon SJ (June 2004). "Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer". Nature Structural & Molecular Biology. 11 (6): 512–518. doi:10.1038/nsmb775. PMID 15133502. S2CID 7354915.