InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Brca1

Summary

InnateDB Protein

IDBP-212220.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Brca1

Protein Name

breast cancer 1

Synonyms

Species

Mus musculus

Ensembl Protein

ENSMUSP00000017290

InnateDB Gene

IDBG-212218 (Brca1)

Protein Structure

UniProt Annotation

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 E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. 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 normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. 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 (By similarity). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. {ECO:0000250, ECO:0000269PubMed:12360400}.

Subcellular Localization

Nucleus {ECO:0000250}. Chromosome {ECO:0000269PubMed:22549958, ECO:0000269PubMed:23039116}. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by the BRCA1-A complex. {ECO:0000250}.

Disease Associations

Tissue Specificity

In the embryo, expressed in otic vesicles at day 9.5. At day 10.5, this expression decreases and high levels are found in the neuroectoderm. At days 11-12.5, high levels in differentiating keratinocytes and whisker pad primordia. At days 14-17, expression also observed in kidney epithelial cells. In the adult, highest levels found in spleen, thymus, lymph nodes, epithelial organs, and alveolar and ductal epithelial cells of the mammary gland. Very low levels in brain, kidney, and skin. No expression in heart, liver or lung.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 26 experimentally validated interaction(s) in this database.
They are also associated with 389 interaction(s) predicted by orthology.

Experimentally validated
Total	26 [view]
Protein-Protein	25 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	389 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003684	damaged DNA binding
GO:0003723	RNA binding
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity
GO:0044212	transcription regulatory region DNA binding
GO:0046872	metal ion binding

Biological Process

GO:0006260	DNA replication
GO:0006281	DNA repair
GO:0006310	DNA recombination
GO:0006349	regulation of gene expression by genetic imprinting
GO:0006633	fatty acid biosynthetic process
GO:0006974	cellular response to DNA damage stimulus
GO:0007098	centrosome cycle
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009048	dosage compensation by inactivation of X chromosome
GO:0035066	positive regulation of histone acetylation
GO:0035067	negative regulation of histone acetylation
GO:0043009	chordate embryonic development
GO:0044030	regulation of DNA methylation
GO:0045717	negative regulation of fatty acid biosynthetic process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0051298	centrosome duplication
GO:0051571	positive regulation of histone H3-K4 methylation
GO:0051572	negative regulation of histone H3-K4 methylation
GO:0051573	negative regulation of histone H3-K9 methylation
GO:0051574	positive regulation of histone H3-K9 methylation
GO:0051865	protein autoubiquitination
GO:0070512	positive regulation of histone H4-K20 methylation
GO:0085020	protein K6-linked ubiquitination
GO:2000617	positive regulation of histone H3-K9 acetylation
GO:2000620	positive regulation of histone H4-K16 acetylation

Cellular Component

GO:0000793	condensed chromosome
GO:0000794	condensed nuclear chromosome
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005694	chromosome
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0005886	plasma membrane
GO:0030529	ribonucleoprotein complex
GO:0031436	BRCA1-BARD1 complex

Protein Structure and Domains

PDB ID

MGI:104537

InterPro

IPR001357 BRCT domain
IPR001841 Zinc finger, RING-type
IPR011364 Breast cancer type 1 susceptibility protein (BRCA1)
IPR018957 Zinc finger, C3HC4 RING-type

PFAM

PF00533
PF12738
PF13639
PF14634
PF00097

PRINTS

PR00493

PIRSF

PIRSF001734

SMART

SM00292
SM00184

TIGRFAMs

Post-translational Modifications

Modification

Cross-References