UniProt functional annotation for Q96RL1



	UniProt functional annotation for Q96RL1

UniProt code: Q96RL1.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.38). 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. {ECO:0000269|PubMed:12080054, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17621610, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19328070, ECO:0000269|PubMed:24627472, ECO:0000269|Ref.38}.

Subunit: Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:24075985). Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:17525341, PubMed:17525342, PubMed:19261746, PubMed:19261749). In the BRCA1-A complex, interacts directly with ABRAXAS1 (PubMed:17643121, PubMed:17643122, PubMed:19261749, PubMed:19261748, PubMed:18077395). Interacts with UBE2I (PubMed:17698038). Interacts with NR6A1 (PubMed:12080054). Interacts with ESR1 (PubMed:17311814). Interacts with TSP57 (By similarity). Interacts with TRAIP (PubMed:26781088). {ECO:0000250|UniProtKB:Q5U5Q9, ECO:0000269|PubMed:12080054, ECO:0000269|PubMed:17311814, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122, ECO:0000269|PubMed:17698038, ECO:0000269|PubMed:18077395, ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19261749, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:26781088}.

Subcellular location: Nucleus {ECO:0000269|PubMed:12080054, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17621610, ECO:0000269|PubMed:17643121}. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs).

Tissue specificity: Expressed in testis, ovary, thymus and heart. Expressed in germ cells of the testis. {ECO:0000269|PubMed:12080054}.

Domain: The tandem UIM domains form a continuous 60 Angstrom-long alpha-helix and mediate binding to 'Lys-63'-linked ubiquitins. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties and recognize an 'Ile-44'-centered hydrophobic patch. Since UIMs don't interact with the 'Lys-63' isopeptide bond the UIM-linker region between the 2 UIM domains determines the selectivity for 'Lys-63'-linkage, and its length is very important for specificity. {ECO:0000250|UniProtKB:Q5U5Q9, ECO:0000269|PubMed:19328070, ECO:0000269|PubMed:24627472, ECO:0000269|Ref.38}.

Domain: The Abraxas-interacting region (AIR) mediates the interaction with ABRAXAS1. {ECO:0000269|PubMed:19328070}.

Ptm: Sumoylated. {ECO:0000269|PubMed:17698038}.

Ptm: Phosphorylated upon DNA damage by ATM or ATR. {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17621610, ECO:0000269|PubMed:18519686}.

Similarity: Belongs to the RAP80 family. {ECO:0000305}.

Sequence caution: Sequence=AAH06078.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.38). 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. {ECO:0000269\|PubMed:12080054, ECO:0000269\|PubMed:17525340, ECO:0000269\|PubMed:17525341, ECO:0000269\|PubMed:17525342, ECO:0000269\|PubMed:17621610, ECO:0000269\|PubMed:17643121, ECO:0000269\|PubMed:19015238, ECO:0000269\|PubMed:19202061, ECO:0000269\|PubMed:19261748, ECO:0000269\|PubMed:19328070, ECO:0000269\|PubMed:24627472, ECO:0000269\|Ref.38}.


Subunit:		Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:24075985). Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:17525341, PubMed:17525342, PubMed:19261746, PubMed:19261749). In the BRCA1-A complex, interacts directly with ABRAXAS1 (PubMed:17643121, PubMed:17643122, PubMed:19261749, PubMed:19261748, PubMed:18077395). Interacts with UBE2I (PubMed:17698038). Interacts with NR6A1 (PubMed:12080054). Interacts with ESR1 (PubMed:17311814). Interacts with TSP57 (By similarity). Interacts with TRAIP (PubMed:26781088). {ECO:0000250\|UniProtKB:Q5U5Q9, ECO:0000269\|PubMed:12080054, ECO:0000269\|PubMed:17311814, ECO:0000269\|PubMed:17525341, ECO:0000269\|PubMed:17525342, ECO:0000269\|PubMed:17643121, ECO:0000269\|PubMed:17643122, ECO:0000269\|PubMed:17698038, ECO:0000269\|PubMed:18077395, ECO:0000269\|PubMed:19261746, ECO:0000269\|PubMed:19261748, ECO:0000269\|PubMed:19261749, ECO:0000269\|PubMed:24075985, ECO:0000269\|PubMed:26781088}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:12080054, ECO:0000269\|PubMed:17525340, ECO:0000269\|PubMed:17525341, ECO:0000269\|PubMed:17525342, ECO:0000269\|PubMed:17621610, ECO:0000269\|PubMed:17643121}. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs).
Tissue specificity:		Expressed in testis, ovary, thymus and heart. Expressed in germ cells of the testis. {ECO:0000269\|PubMed:12080054}.
Domain:		The tandem UIM domains form a continuous 60 Angstrom-long alpha-helix and mediate binding to 'Lys-63'-linked ubiquitins. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties and recognize an 'Ile-44'-centered hydrophobic patch. Since UIMs don't interact with the 'Lys-63' isopeptide bond the UIM-linker region between the 2 UIM domains determines the selectivity for 'Lys-63'-linkage, and its length is very important for specificity. {ECO:0000250\|UniProtKB:Q5U5Q9, ECO:0000269\|PubMed:19328070, ECO:0000269\|PubMed:24627472, ECO:0000269\|Ref.38}.
Domain:		The Abraxas-interacting region (AIR) mediates the interaction with ABRAXAS1. {ECO:0000269\|PubMed:19328070}.
Ptm:		Sumoylated. {ECO:0000269\|PubMed:17698038}.
Ptm:		Phosphorylated upon DNA damage by ATM or ATR. {ECO:0000269\|PubMed:17525340, ECO:0000269\|PubMed:17525341, ECO:0000269\|PubMed:17525342, ECO:0000269\|PubMed:17621610, ECO:0000269\|PubMed:18519686}.
Similarity:		Belongs to the RAP80 family. {ECO:0000305}.
Sequence caution:		Sequence=AAH06078.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};