BRCA1-A complex subunit RAP80

Function

Ubiquitin-binding protein. Specifically recognizes and binds 'Lys-63'-linked ubiquitin. Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1.

Classification

Family (Pfam)

PF18282 RAP80_UIM

InterPro

Rad18_UBZ4, RAP80, RAP80_UIM, UIM_dom

Functional cluster

Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 4

• 2MKF NMR
• 2MKG NMR
• 2N9E NMR
• 2RR9 NMR

A predicted model is available from AlphaFold.

Gene Ontology · 19

• GO:0070531 BRCA1-A complex
• GO:0016604 nuclear body
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0035861 site of double-strand break
• GO:0003677 DNA binding
• GO:0042393 histone binding
• GO:0070530 K63-linked polyubiquitin modification-dependent protein binding
• GO:0061649 ubiquitin-modified histone reader activity
• GO:0008270 zinc ion binding
• GO:0140861 DNA repair-dependent chromatin remodeling
• GO:0006351 DNA-templated transcription
• GO:0006302 double-strand break repair
• GO:0007095 mitotic G2 DNA damage checkpoint signaling
• GO:0044818 mitotic G2/M transition checkpoint
• GO:0045892 negative regulation of DNA-templated transcription
• GO:0045739 positive regulation of DNA repair
• GO:0006282 regulation of DNA repair
• GO:0010212 response to ionizing radiation

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• BRCA1-A complex subunit RAP80 0.99
• BRCA1-A complex subunit RAP80 0.98
• BRCA1-A complex subunit RAP80 0.96
• Protein DBF4 homolog A 0.81
• Protein DBF4 homolog A 0.81
• Protein DBF4 homolog A 0.80
• DNA endonuclease RBBP8 0.78
• Structure-specific endonuclease subunit SLX4 0.78
• Microcephalin 0.78
• Microcephalin 0.78
• Aurora kinase A- and ninein-interacting protein 0.78
• Microcephalin 0.77

Co-cited proteins · studied together in the literature

• BRCA1-A complex subunit Abraxas 1 9 shared papers
• Lys-63-specific deubiquitinase BRCC36 7 shared papers
• E3 ubiquitin-protein ligase RNF8 3 shared papers
• E3 ubiquitin-protein ligase TRAIP 1 shared papers
• BRISC and BRCA1-A complex member 2 5 shared papers
• Nuclear receptor subfamily 6 group A member 1 1 shared papers
• BRISC and BRCA1-A complex member 1 4 shared papers
• Breast cancer type 1 susceptibility protein 6 shared papers
• Nuclear receptor subfamily 6 group A member 1 1 shared papers
• BRCA1-associated RING domain protein 1 2 shared papers
• E3 ubiquitin-protein ligase RNF169 1 shared papers
• BRISC complex subunit Abraxas 2 3 shared papers

Literature · 37 cited papers

• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage. Nat. Commun. · 2016
• SUMO-2 orchestrates chromatin modifiers in response to DNA damage. Cell Rep. · 2015
• 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
• Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
• Molecular basis for impaired DNA damage response function associated with the RAP80 E81 defect. J. Biol. Chem. · 2014
• A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon responses. Cell Rep. · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Tandem protein interaction modules organize the ubiquitin-dependent response to DNA double-strand breaks. Mol. Cell · 2012
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• … and 25 more in the literature graph