Breast cancer type 1 susceptibility protein homolog

Function

E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Required for FANCD2 targeting to sites of DNA damage. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator.

Classification

Family (Pfam)

PF00533 BRCT, PF12820 BRCT_assoc, PF00097 zf-C3HC4

InterPro

BRCA1, BRCA1-associated, BRCA1_serine_dom, BRCT_dom, BRCT_dom_sf, Znf_C3HC4_RING-type, Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS

Functional cluster

Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 1

• 7K3S NMR

A predicted model is available from AlphaFold.

Gene Ontology · 76

• GO:0070531 BRCA1-A complex
• GO:0070532 BRCA1-B complex
• GO:0031436 BRCA1-BARD1 complex
• GO:0070533 BRCA1-C complex
• GO:0005813 centrosome
• GO:0005694 chromosome
• GO:0000793 condensed chromosome
• GO:0000794 condensed nuclear chromosome
• GO:0005737 cytoplasm
• GO:1990391 DNA repair complex
• GO:0000800 lateral element
• GO:0005759 mitochondrial matrix
• GO:0016604 nuclear body
• GO:0000152 nuclear ubiquitin ligase complex
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0032991 protein-containing complex
• GO:1990904 ribonucleoprotein complex
• GO:0001741 XY body
• GO:0003682 chromatin binding
• GO:0003684 damaged DNA binding
• GO:0019899 enzyme binding
• GO:0042802 identical protein binding
• GO:0002039 p53 binding
• GO:0003723 RNA binding
• GO:0070063 RNA polymerase binding
• GO:0000976 transcription cis-regulatory region binding
• GO:0003713 transcription coactivator activity
• GO:0061630 ubiquitin protein ligase activity
• GO:0031625 ubiquitin protein ligase binding
• GO:0004842 ubiquitin-protein transferase activity
• GO:0008270 zinc ion binding
• GO:0071681 cellular response to indole-3-methanol
• GO:0071479 cellular response to ionizing radiation
• GO:0071356 cellular response to tumor necrosis factor
• GO:0007098 centrosome cycle
• GO:0051298 centrosome duplication
• GO:0043009 chordate embryonic development
• GO:0007059 chromosome segregation
• GO:0006974 DNA damage response
• GO:0006301 DNA damage tolerance
• GO:0006281 DNA repair
• GO:0110025 DNA strand resection involved in replication fork processing
• GO:0006351 DNA-templated transcription
• GO:0006302 double-strand break repair
• GO:0000724 double-strand break repair via homologous recombination
• GO:0006633 fatty acid biosynthetic process
• GO:0035825 homologous recombination
• GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
• GO:0007095 mitotic G2 DNA damage checkpoint signaling
• GO:0044818 mitotic G2/M transition checkpoint
• GO:0030308 negative regulation of cell growth
• GO:0045892 negative regulation of DNA-templated transcription
• GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
• GO:0045717 negative regulation of fatty acid biosynthetic process
• GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation
• GO:0033147 negative regulation of intracellular estrogen receptor signaling pathway
• GO:2000378 negative regulation of reactive oxygen species metabolic process
• GO:0045766 positive regulation of angiogenesis
• GO:0045787 positive regulation of cell cycle
• GO:0045739 positive regulation of DNA repair
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0010628 positive regulation of gene expression
• GO:0042307 positive regulation of protein import into nucleus
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0010575 positive regulation of vascular endothelial growth factor production
• GO:0051865 protein autoubiquitination
• GO:0085020 protein K6-linked ubiquitination
• GO:0016567 protein ubiquitination
• GO:0060816 random inactivation of X chromosome
• GO:0051726 regulation of cell cycle
• GO:2000001 regulation of DNA damage checkpoint
• GO:0006282 regulation of DNA repair
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0010212 response to ionizing radiation

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Breast cancer type 1 susceptibility protein homolog 0.97
• Breast cancer type 1 susceptibility protein 0.97
• Breast cancer type 1 susceptibility protein homolog 0.96
• Breast cancer type 1 susceptibility protein homolog 0.96
• Breast cancer type 1 susceptibility protein homolog 0.96
• Breast cancer type 1 susceptibility protein homolog 0.96
• Breast cancer type 1 susceptibility protein homolog 0.96
• Breast cancer type 1 susceptibility protein homolog 0.95
• Ankyrin repeat domain-containing protein 31 0.91
• Protein TOPAZ1 0.91
• Protein TOPAZ1 0.90
• Protein TOPAZ1 0.90

Co-cited proteins · studied together in the literature

• Mediator of DNA damage checkpoint protein 1 1 shared papers
• HORMA domain-containing protein 2 2 shared papers
• Serine/threonine-protein kinase ATR 2 shared papers
• DNA topoisomerase 2-binding protein 1 1 shared papers
• Acetyl-CoA carboxylase 1 1 shared papers
• Acetyl-CoA carboxylase 1 1 shared papers
• Histone H2AX 1 shared papers
• HORMA domain-containing protein 1 1 shared papers
• Meiotic recombination protein DMC1 homolog 1 shared papers
• Breast cancer type 1 susceptibility protein 1 shared papers

Literature · 12 cited papers

• HORMAD2 is essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity. Genes Cells · 2012
• Meiotic DNA double-strand breaks and chromosome asynapsis in mice are monitored by distinct HORMAD2-independent and -dependent mechanisms. Genes Dev. · 2012
• A tissue-specific atlas of mouse protein phosphorylation and expression. Cell · 2010
• Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. · 2009
• ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science · 2007
• BRCA1 interacts with acetyl-CoA carboxylase through its tandem of BRCT domains. Oncogene · 2002
• Murine Brca1: sequence and significance for human missense mutations. Hum. Mol. Genet. · 1995
• Mouse Brca1: localization sequence analysis and identification of evolutionarily conserved domains. Hum. Mol. Genet. · 1995
• Isolation of the mouse homologue of BRCA1 and genetic mapping to mouse chromosome 11. Genomics · 1995
• The murine homolog of the human breast and ovarian cancer susceptibility gene Brca1 maps to mouse chromosome 11D. Hum. Genet. · 1996
• Expression of Brca1 is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice. Genes Dev. · 1995
• The developmental pattern of Brca1 expression implies a role in differentiation of the breast and other tissues. Nat. Genet. · 1995