BRIP1
Domain
4Fe-4S iron-sulfur-binding is required for helicase activity.
Function
DNA-dependent ATPase and 5'-3' DNA helicase required for the maintenance of chromosomal stability (PubMed:11301010, PubMed:14983014, PubMed:16116421, PubMed:16153896, PubMed:17596542, PubMed:36608669). Acts late in the Fanconi anemia pathway, after FANCD2 ubiquitination (PubMed:14983014, PubMed:16153896). Involved in the repair of DNA double-strand breaks by homologous recombination in a manner that depends on its association with BRCA1 (PubMed:14983014, PubMed:16153896). Involved in the repair of abasic sites at replication forks by promoting the degradation of DNA-protein cross-links: acts by catalyzing unfolding of HMCES DNA-protein cross-link via its helicase activity, exposing the underlying DNA and enabling cleavage of the DNA-protein adduct by the SPRTN metalloprotease (PubMed:16116421, PubMed:36608669). Can unwind RNA:DNA substrates (PubMed:14983014). Unwinds G-quadruplex DNA; unwinding requires a 5'-single stranded tail (PubMed:18426915, PubMed:20639400).
Involvement in disease
Breast cancer
BC
A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Fanconi anemia complementation group J
FANCJ
A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated. Phosphorylation is necessary for interaction with BRCA1, and is cell-cycle regulated.
Acetylation at Lys-1249 facilitates DNA end processing required for repair and checkpoint signaling.
Sequence Similarities
Belongs to the DEAD box helicase family. DEAH subfamily.
Tissue Specificity
Ubiquitously expressed, with highest levels in testis.
Cellular localization
- Nucleus
- Cytoplasm
Alternative names
BACH1, FANCJ, BRIP1, Fanconi anemia group J protein, BRCA1-associated C-terminal helicase 1, BRCA1-interacting protein C-terminal helicase 1, DNA 5'-3' helicase FANCJ, BRCA1-interacting protein 1