retinoid X receptor-interacting protein 110; BRCA1-A complex subunit RAP80; receptor-associated protein 80; ubiquitin interaction motif-containing protein 1 (UIMC1, RAP80, RXRIP110)

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

General

nuclear protein phosphoprotein zinc finger protein

Properties

SIZE: entity length = 719 aa MW = 80 kD COMPARTMENT: cell nucleus MOTIF: silencer element SITE: 1-101 MOTIF: Ser phosphorylation site {S44} Ser phosphorylation site {S46} LR {60-78} UIM {79-96} glutamate-rich region {81-108} MOTIF: glutamate residue (SEVERAL) UIM-linker {97-103} NR6A1 interaction {100-200} MOTIF: Ser phosphorylation site {S101} UIM {104-124} Ser phosphorylation site {S140} Ser phosphorylation site {S205} AIR {270-400} NR6A1 interaction {400-500} MOTIF: Ser phosphorylation site {S402} Ser phosphorylation site {S415} Ser phosphorylation site {S419} Zinc-finger-like region {505-582} Ser phosphorylation site {S597} Ser phosphorylation site {S627} Ser phosphorylation site {S653} Ser phosphorylation site {S677}

Database Correlations

OMIM 609433 UniProt Q96RL1 Entrez Gene 51720 Kegg hsa:51720

References

UniProt :accession Q96RL1