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Fanconi anemia group D2 protein; protein FACD2 (FANCD2, FACD)
Function:
1) required for maintenance of chromosomal stability
2) promotes accurate & efficient pairing of homologs during meiosis
3) involved in repair of DNA double-strand breaks, both by homologous recombination & single-strand annealing
4) participates in S phase & G2 phase checkpoint activation upon DNA damage
5) promotes BRCA2/FANCD1 loading onto damaged chromatin
6) B-cell immunoglobulin isotype switching putative
7) interacts FANCE, USP1, MEN1
8) ubiquitinated form interacts with BRCA1, BRCA2, BLM
9) monoubiquitinated on Lys-561 during S phase & upon genotoxic stress
10) deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed
11) monoubiquitination requires the FA complex, RPA1 & ATR, & is mediated by FANCL/PHF9.
12) 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
13) phosphorylated in response to various genotoxic stresses by ATM &/or ATR
14) upon ionizing radiation, phosphorylated by ATM on Ser-222 & Ser-1404
15) phosphorylation on Ser-222 required for S-phase checkpoint activation, but not for ubiquitination, foci formation, or DNA repair
16) 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
Related
Fanconi anemia
General
nuclear protein
phosphoprotein
Properties
SIZE: entity length = 1471 aa
MW = 166 kD
COMPARTMENT: cell nucleus
MOTIF: FANCE interaction {1-291}
MOTIF: Ser phosphorylation site {S21}
Ser phosphorylation site {S167}
Ser phosphorylation site {S178}
Ser phosphorylation site {S222}
BRCA2 interaction {248-359}
Ser phosphorylation site {S592}
Thr phosphorylation site {T596}
Tyr phosphorylation site {Y684}
Ser phosphorylation site {S717}
Ser phosphorylation site {S1401}
Ser phosphorylation site {S1404}
Ser phosphorylation site {S1412}
Ser phosphorylation site {S1418}
Database Correlations
OMIM correlations
UniProt Q9BXW9
Entrez Gene 2177
Kegg hsa:2177
References
- UniProt :accession Q9BXW9
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/FAD.html
- Fanconi Anemia mutation Database
http://www.rockefeller.edu/fanconi/mutate/jumpd2.html
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/FANCD2
- NIEHS-SNPs
http://egp.gs.washington.edu/data/fancd2/