FAM175A

FAM175A (Family With Sequence Similarity 175 Member A) is a Protein Coding gene. Diseases associated with FAM175A include breast cancer. Among its related pathways are Cell Cycle, Mitotic and DNA Double-Strand Break Repair. GO annotations related to this gene include polyubiquitin binding. An important paralog of this gene is FAM175B.

Full Name

Family with sequence similarity 175 member A

Research Area

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.

Biological Process

Attachment of spindle microtubules to kinetochore Source: GO_Central
Chromatin organization Source: UniProtKB-KW
Double-strand break repair Source: UniProtKB
Mitotic G2 DNA damage checkpoint signaling Source: UniProtKB
Mitotic spindle assembly Source: GO_Central
Positive regulation of DNA repair Source: UniProtKB
Protein K63-linked deubiquitination Source: GO_Central
Response to ionizing radiation Source: UniProtKB

Cellular Location

Nucleus. Localizes at sites of DNA damage at double-strand breaks (DSBs).

Involvement in disease

Breast cancer (BC):
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.

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).