retinoid X receptor-interacting protein 110; BRCA1-A complex subunit RAP80; receptor-associated protein 80; ubiquitin interaction motif-containing protein 1 (UIMC1, RAP80, RXRIP110)
Jump to navigation
Jump to search
Function
- ubiquitin-binding protein
- specifically recognizes & binds Lys-63-linked ubiquitin
- role in the BRCA1-A complex by specifically binding Lys-63- linked ubiquitinated histone H2A & histone H2AX at DNA lesions, targeting the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks
- the BRCA1-A complex also possesses deubiquitinase activity that specifically removes Lys-63-linked ubiquitin on histone H2A & histone H2AX
- weakly binds monoubiquitin but with much less affinity than Lys-63-linked ubiquitin
- may interact with monoubiquitinated histone H2A & histone H2B
- does not bind Lys-48-linked ubiquitin
- may indirectly act as a transcriptional repressor by inhibiting interaction of NR6A1 with the corepressor NCOR1
- sumoylated
- phosphorylated upon DNA damage by ATM or ATR
- interacts with TSP57 (putative)
- component of the BRCA1-A complex
- in the BRCA1-A complex, interacts directly with FAM175A/Abraxas
- interacts with ESR1, NR6A1 & UBE2I
Structure
- the UIM-linker region between the 2 UIM repeats determines selectivity for Lys-63-linked ubiquitin
- the length of the linker is important
- the linker reduces the flexibility between the UIM repeats & promotes high-affinity & linkage-selective interactions
- the Abraxas-interacting region (AIR) mediates interaction with FAM175A/Abraxas
- belongs to the RAP80 family
- contains 2 UIM (ubiquitin-interacting motif) repeats
Compartment
- nucleus
- localizes at sites of DNA damage at double-strand breaks
Alternative splicing
named isoforms=5
Expression
- expressed in testis, ovary, thymus, heart
- expressed in germ cells of testis