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Fanconi anemia, complementation group D2
External IDs OMIM613984 MGI2448480 HomoloGene13212 GeneCards: FANCD2 Gene
Species Human Mouse
Entrez 2177 211651
Ensembl ENSG00000144554 ENSMUSG00000034023
UniProt Q9BXW9 Q80V62
RefSeq (mRNA) NM_001018115 NM_001033244
RefSeq (protein) NP_001018125 NP_001028416
Location (UCSC) Chr 3:
10.07 – 10.14 Mb
Chr 6:
113.53 – 113.6 Mb
PubMed search [1] [2]

Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene.[1][2][3][4] The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2 (this gene), FANCE, FANCF, FANCG, and FANCL.


Fanconi anemia is a genetically homozygous recessive disorder characterized by chromosomal instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group D2. This protein is monoubiquitinated in response to DNA damage, resulting in its localization to nuclear foci with other proteins (BRCA1 and BRCA2) involved in homology-directed DNA repair. This monoubiquitination is required for interaction with the nuclease FAN1. Alternative splicing results in two transcript variants encoding different isoforms.[4]

Clinical significance[edit]

Tobacco smoke suppresses the expression of FANCD2, which codes for a DNA damage "caretaker" or repair mechanism.[5]


FANCD2 has been shown to interact with:


  1. ^ Whitney M, Thayer M, Reifsteck C, Olson S, Smith L, Jakobs PM, Leach R, Naylor S, Joenje H, Grompe M (December 1995). "Microcell mediated chromosome transfer maps the Fanconi anaemia group D gene to chromosome 3p". Nat Genet 11 (3): 341–3. doi:10.1038/ng1195-341. PMID 7581463. 
  2. ^ Timmers C, Taniguchi T, Hejna J, Reifsteck C, Lucas L, Bruun D, Thayer M, Cox B, Olson S, D'Andrea AD, Moses R, Grompe M (March 2001). "Positional cloning of a novel Fanconi anemia gene, FANCD2". Mol Cell 7 (2): 241–8. doi:10.1016/S1097-2765(01)00172-1. PMID 11239453. 
  3. ^ Hays LE, Zodrow DM, Yates JE, Deffebach ME, Jacoby DB, Olson SB, Pankow JF, Bagby GC (May 2008). "Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression". Br J Cancer 98 (10): 1653–61. doi:10.1038/sj.bjc.6604362. PMC 2391131. PMID 18475298. 
  4. ^ a b "Entrez Gene: FANCD2 Fanconi anemia, complementation group D2". 
  5. ^ Hays LE, Zodrow DM, Yates JE, Deffebach ME, Jacoby DB, Olson SB, Pankow JF, Bagby GC (May 2008). "Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression". Br. J. Cancer 98 (10): 1653–61. doi:10.1038/sj.bjc.6604362. PMC 2391131. PMID 18475298. 
  6. ^ Yuan F, El Hokayem J, Zhou W, Zhang Y (Sep 4, 2009). "FANCI protein binds to DNA and interacts with FANCD2 to recognize branched structures.". The Journal of biological chemistry 284 (36): 24443–52. doi:10.1074/jbc.m109.016006. PMID 19561358. 
  7. ^ Joo W, Xu G, Persky NS, Smogorzewska A, Rudge DG, Buzovetsky O, Elledge SJ, Pavletich NP (Jul 15, 2011). "Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway.". Science (New York, N.Y.) 333 (6040): 312–6. doi:10.1126/science.1205805. PMID 21764741. 
  8. ^ Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Kim ST, Lane WS, Kastan MB, D'Andrea AD (May 2002). "Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways". Cell 109 (4): 459–72. doi:10.1016/S0092-8674(02)00747-X. PMID 12086603. 
  9. ^ a b Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (October 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Exp. Cell Res. 289 (2): 211–21. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622. 
  10. ^ a b Vandenberg CJ, Gergely F, Ong CY, Pace P, Mallery DL, Hiom K, Patel KJ (July 2003). "BRCA1-independent ubiquitination of FANCD2". Mol. Cell 12 (1): 247–54. doi:10.1016/S1097-2765(03)00281-8. PMID 12887909. 
  11. ^ Wang X, Andreassen PR, D'Andrea AD (July 2004). "Functional Interaction of Monoubiquitinated FANCD2 and BRCA2/FANCD1 in Chromatin". Mol. Cell. Biol. 24 (13): 5850–62. doi:10.1128/MCB.24.13.5850-5862.2004. PMC 480901. PMID 15199141. 
  12. ^ a b Hussain S, Wilson JB, Medhurst AL, Hejna J, Witt E, Ananth S, Davies A, Masson JY, Moses R, West SC, de Winter JP, Ashworth A, Jones NJ, Mathew CG (June 2004). "Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways". Hum. Mol. Genet. 13 (12): 1241–8. doi:10.1093/hmg/ddh135. PMID 15115758. 
  13. ^ a b Hejna J, Holtorf M, Hines J, Mathewson L, Hemphill A, Al-Dhalimy M, Olson SB, Moses RE (April 2008). "Tip60 Is Required for DNA Interstrand Cross-link Repair in the Fanconi Anemia Pathway". J. Biol. Chem. 283 (15): 9844–51. doi:10.1074/jbc.M709076200. PMC 2398728. PMID 18263878. 
  14. ^ Gordon SM, Buchwald M (July 2003). "Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems". Blood 102 (1): 136–41. doi:10.1182/blood-2002-11-3517. PMID 12649160. 
  15. ^ Pace P, Johnson M, Tan WM, Mosedale G, Sng C, Hoatlin M, de Winter J, Joenje H, Gergely F, Patel KJ (July 2002). "FANCE: the link between Fanconi anaemia complex assembly and activity". EMBO J. 21 (13): 3414–23. doi:10.1093/emboj/cdf355. PMC 125396. PMID 12093742. 
  16. ^ Jin S, Mao H, Schnepp RW, Sykes SM, Silva AC, D'Andrea AD, Hua X (July 2003). "Menin associates with FANCD2, a protein involved in repair of DNA damage". Cancer Res. 63 (14): 4204–10. PMID 12874027. 

Further reading[edit]