UniProt functional annotation for Q6UWZ7



	UniProt functional annotation for Q6UWZ7

UniProt code: Q6UWZ7.

Organism: Homo sapiens (Human).

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

Function: Involved in DNA damage response and double-strand break (DSB) repair. Component of the BRCA1-A complex, acting as a central scaffold protein that assembles the various components of the complex and mediates the recruitment of BRCA1. The BRCA1-A complex specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at DSBs. This complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122, ECO:0000269|PubMed:18077395, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:22357538, ECO:0000269|PubMed:26778126}.

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 BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the complex, interacts directly with UIMC1/RAP80, BRCC3/BRCC36 and BABAM2. Interacts directly (when phosphorylated at Ser-406) with BRCA1. Homodimer. The homodimer interacts directly (when phosphorylated at Ser-404 and Ser-406) with two BRCA1 chains, giving rise to a heterotetramer. Binds polyubiquitin. {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122, ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19261749, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:24316840, ECO:0000269|PubMed:26778126}.

Subcellular location: Nucleus {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122}. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). {ECO:0000305}.

Ptm: Phosphorylation of Ser-406 of the pSXXF motif by ATM or ATR constitutes a specific recognition motif for the BRCT domain of BRCA1 (PubMed:17643121, PubMed:17525340, PubMed:17643122). Ionizing radiation promotes rapid phosphorylation at Ser-404 and Ser-406 by ATM; this promotes recruitment of BRCA1 to sites of DNA damage (PubMed:26778126). {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122, ECO:0000269|PubMed:26778126}.

Disease: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:22357538, ECO:0000269|PubMed:25105795}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity: Belongs to the FAM175 family. Abraxas subfamily. {ECO:0000305}.

Sequence caution: Sequence=AAH39573.1; Type=Erroneous initiation; Note=Truncated N-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:		Involved in DNA damage response and double-strand break (DSB) repair. Component of the BRCA1-A complex, acting as a central scaffold protein that assembles the various components of the complex and mediates the recruitment of BRCA1. The BRCA1-A complex specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at DSBs. This complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. {ECO:0000269\|PubMed:17525340, ECO:0000269\|PubMed:17643121, ECO:0000269\|PubMed:17643122, ECO:0000269\|PubMed:18077395, ECO:0000269\|PubMed:19261748, ECO:0000269\|PubMed:22357538, ECO:0000269\|PubMed:26778126}.


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 BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the complex, interacts directly with UIMC1/RAP80, BRCC3/BRCC36 and BABAM2. Interacts directly (when phosphorylated at Ser-406) with BRCA1. Homodimer. The homodimer interacts directly (when phosphorylated at Ser-404 and Ser-406) with two BRCA1 chains, giving rise to a heterotetramer. Binds polyubiquitin. {ECO:0000269\|PubMed:17525340, ECO:0000269\|PubMed:17643121, ECO:0000269\|PubMed:17643122, ECO:0000269\|PubMed:19261746, ECO:0000269\|PubMed:19261748, ECO:0000269\|PubMed:19261749, ECO:0000269\|PubMed:24075985, ECO:0000269\|PubMed:24316840, ECO:0000269\|PubMed:26778126}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:17525340, ECO:0000269\|PubMed:17643121, ECO:0000269\|PubMed:17643122}. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). {ECO:0000305}.
Ptm:		Phosphorylation of Ser-406 of the pSXXF motif by ATM or ATR constitutes a specific recognition motif for the BRCT domain of BRCA1 (PubMed:17643121, PubMed:17525340, PubMed:17643122). Ionizing radiation promotes rapid phosphorylation at Ser-404 and Ser-406 by ATM; this promotes recruitment of BRCA1 to sites of DNA damage (PubMed:26778126). {ECO:0000269\|PubMed:17525340, ECO:0000269\|PubMed:17643121, ECO:0000269\|PubMed:17643122, ECO:0000269\|PubMed:26778126}.
Disease:		Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269\|PubMed:22357538, ECO:0000269\|PubMed:25105795}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Similarity:		Belongs to the FAM175 family. Abraxas subfamily. {ECO:0000305}.
Sequence caution:		Sequence=AAH39573.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};