BRCA1-associated RING domain protein 1

Function

E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II stability by inhibiting pre-mRNA 3' cleavage.

Classification

Family (Pfam)

PF12796 Ank_2, PF00533 BRCT, PF14835 zf-RING_6

InterPro

Ankyrin_rpt, Ankyrin_rpt-contain_sf, BARD1_Znf-RING, BRCT_dom, BRCT_dom_sf, Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS

Functional cluster

Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 11

• 1JM7 NMR
• 2NTE X-ray 1.90A
• 2R1Z X-ray 2.10A
• 3C5R X-ray 2.00A
• 3FA2 X-ray 2.20A
• 6M14 X-ray 1.88A
• 7E8I EM 3.10A
• 7JZV EM 3.90A
• 7LYB EM 3.28A
• 7LYC EM 2.94A
• 8GRQ EM 3.87A

A predicted model is available from AlphaFold.

Gene Ontology · 38

• GO:0070531 BRCA1-A complex
• GO:0031436 BRCA1-BARD1 complex
• GO:0005737 cytoplasm
• GO:0016607 nuclear speck
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0000151 ubiquitin ligase complex
• GO:0140863 histone H2AK127 ubiquitin ligase activity
• GO:0140864 histone H2AK129 ubiquitin ligase activity
• GO:0019900 kinase binding
• GO:0046982 protein heterodimerization activity
• GO:0042803 protein homodimerization activity
• GO:0003723 RNA binding
• GO:0061630 ubiquitin protein ligase activity
• GO:0061649 ubiquitin-modified histone reader activity
• GO:0004842 ubiquitin-protein transferase activity
• GO:0008270 zinc ion binding
• GO:0071479 cellular response to ionizing radiation
• GO:0006338 chromatin remodeling
• GO:0006974 DNA damage response
• GO:0006281 DNA repair
• GO:0110025 DNA strand resection involved in replication fork processing
• GO:0035825 homologous recombination
• GO:0044818 mitotic G2/M transition checkpoint
• GO:0043066 negative regulation of apoptotic process
• GO:0045786 negative regulation of cell cycle
• GO:0031441 negative regulation of mRNA 3'-end processing
• GO:0046826 negative regulation of protein export from nucleus
• GO:0043065 positive regulation of apoptotic process
• GO:0045732 positive regulation of protein catabolic process
• GO:0085020 protein K6-linked ubiquitination
• GO:0016567 protein ubiquitination
• GO:0051726 regulation of cell cycle
• GO:2000001 regulation of DNA damage checkpoint
• GO:0006282 regulation of DNA repair
• GO:0042325 regulation of phosphorylation
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0001894 tissue homeostasis

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• BRCA1-associated RING domain protein 1 0.96
• BRCA1-associated RING domain protein 1 0.92
• Protein CHROMATIN REMODELING 4 0.72
• ZZ-type zinc finger-containing protein 3 0.71
• E3 ubiquitin-protein ligase RNF169 0.70
• Cell division cycle-associated protein 2 0.70
• DNA cross-link repair 1A protein 0.70
• Exonuclease 1 0.69
• Cell division cycle-associated protein 2 0.69
• Exonuclease 1 0.69
• E3 ubiquitin-protein ligase rnf168 0.69
• ZZ-type zinc finger-containing protein 3 0.68

Co-cited proteins · studied together in the literature

• Cleavage stimulation factor subunit 1 1 shared papers
• Breast cancer type 1 susceptibility protein 6 shared papers
• UBX domain-containing protein 1 1 shared papers
• BRCA1-A complex subunit Abraxas 1 2 shared papers
• BRCA1-A complex subunit RAP80 2 shared papers
• BRISC and BRCA1-A complex member 1 1 shared papers
• BRISC complex subunit Abraxas 2 1 shared papers
• BRISC and BRCA1-A complex member 2 1 shared papers
• Lys-63-specific deubiquitinase BRCC36 1 shared papers

Literature · 22 cited papers

• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability. Mol. Cell. Proteomics · 2015
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor and inhibits its enzymatic function. Mol. Cell. Biol. · 2010
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
• NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control. Genes Dev. · 2009
• The BARD1 C-terminal domain structure and interactions with polyadenylation factor CstF-50. Biochemistry · 2008
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Crystal structure of the BARD1 ankyrin repeat domain and its functional consequences. J. Biol. Chem. · 2008
• Oncogenic BARD1 isoforms expressed in gynecological cancers. Cancer Res. · 2007
• CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage response. Nat. Struct. Mol. Biol. · 2007
• … and 10 more in the literature graph