Fanconi anemia group D2 protein; protein FACD2 (FANCD2, FACD)

Function

• required for maintenance of chromosomal stability
• promotes accurate & efficient pairing of homologs during meiosis
• involved in repair of DNA double-strand breaks, both by homologous recombination & single-strand annealing
• participates in S phase & G2 phase checkpoint activation upon DNA damage
• promotes BRCA2/FANCD1 loading onto damaged chromatin
• B-cell immunoglobulin isotype switching putative
• interacts FANCE, USP1, MEN1
• ubiquitinated form interacts with BRCA1, BRCA2, BLM
• monoubiquitinated on Lys-561 during S phase & upon genotoxic stress
• deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed
• monoubiquitination requires the FA complex, RPA1 & ATR, & is mediated by FANCL/PHF9.
• ubiquitination is required for binding to chromatin, interaction with BRCA1 & BRCA2, DNA repair, & normal cell cycle progression, but not for phosphorylation on Ser-222 or interaction with MEN1
• phosphorylated in response to various genotoxic stresses by ATM &/or ATR
• upon ionizing radiation, phosphorylated by ATM on Ser-222 & Ser-1404
• phosphorylation on Ser-222 required for S-phase checkpoint activation, but not for ubiquitination, foci formation, or DNA repair
• phosphorylation by ATR on other sites may be required for ubiquitination & foci formation.

Compartment

• nucleus
• concentrates in nuclear foci during S phase & upon genotoxic stress

Alternative splicing

• named isoforms=4;
• isoform 1 less abundant than isoform 2 & may be not functional

Expression

• highly expressed in germinal center cells of spleen, tonsil, reactive lymph nodes, proliferating basal layer of squamous epithelium of tonsil, esophagus, oropharynx, larynx, cervix, cytotrophoblastic cells of placenta, exocrine cells of pancreas, maturing spermatocytes, fetal oocytes, hematopoietic cells of fetal liver & bone marrow

Pathology

• defects in FANCD2 are a cause of Fanconi anemia

More general terms

• nuclear protein
• phosphoprotein

Additional terms

• Fanconi anemia

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=2177
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:2177
• OMIM: https://mirror.omim.org/entry/227646
• OMIM: https://mirror.omim.org/entry/227650
• UniProt: http://www.uniprot.org/uniprot/Q9BXW9.html