Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   
X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

FANCD2 (Fanconi anemia, complementation group D2)

Identity

Other namesFAD
FAD2
FACD
FANCD
HGNC FANCD2
Location 3p25-26
Local_order not far from XPC, in 3p25

DNA/RNA

Description 44 exons; 4356 bp open reading frame; the first exon is non-coding.

Protein

Description 1452 amino acids; 155 kDa (FANCD2-S isoform, for short), and 162 kDa (FANCD2-L isoform, for long) by ubiquitin addition
Expression weak
Localisation nucleus
Function the FA complex is comprised of : FANCA, FANCC, FANCE, FANCF, and FANCG; this complex is only found in the nucleus.
  • FANCA and FANCG form a complex in the cytoplasm, through a N-term FANCA (involving the nuclear localization signal) - FANCG interaction; FANCC join the complex; phosphorylation of FANCA would induce its translocation into the nucleus.This FA complex translocates into the nucleus, where FANCE and FANCF are present; FANCE and FANCF join the complex. The FA complex subsequently interacts with FANCD2 by monoubiquitination of FANCD2 during S phase or following DNA damage. Activated (ubiquinated ) FANCD2 (i.e. FANCD2-L), downstream in the FA pathway, will then interact with other proteins involved in DNA repair, possibly BRCA1; after DNA repair, FANCD2 return to the non-ubiquinated form (FANCD2-S).
  • FANCD2co-localizes with BRCA1 in DNA damaged-induced loci and in the synaptonemal complex of meotic chromosomes as well.
    • Homology significant homologies can be found with proteins from various species

    Implicated in

    Entity Fanconi anaemia (FA); FANCD2 is implicated in the FA complementation group D, a heterogeneous group, with at least 2 genes: FANCD2, and a yet undiscovered FANCD1. FA complementation group D represents about 1% of FA cases. In FA complementation group D patients, the FA complex is normal, in contrast with results found in group A, B (with a yet unknown gene), C, E, F, and G patients.
    Disease Fanconi anaemia is a chromosome instability syndrome/cancer prone disease (at risk of leukaemia and squamous cell carcinoma)
    Prognosis Fanconi anaemia's prognosis is poor; mean survival is 20 years: patients die of bone marrow failure (infections, haemorrhages), leukaemia, or solid cancer.
  • It has recently been shown that significant phenotypic differences were found between the various complementation groups. Patients from the rare groups FA-D, FA-E, and FA-F had somatic abnormalities more frequently.
    • Cytogenetics Spontaneously enhanced chromatid-type aberrations (breaks, gaps, interchanges; increased rate of breaks compared to control, when induced by specific clastogens known as DNA cross-linking agents (e.g. mitomycin C, diepoxybutane).
      

    External links

    Nomenclature
    HGNCFANCD2   3585
    Entrez_GeneFANCD2  2177  Fanconi anemia, complementation group D2
    Cards
    AtlasFAD
    GeneCardsFANCD2
    EnsemblFANCD2 [Search_View]   ENSG00000144554 [Gene_View]
    GenatlasFANCD2
    GeneLynxFANCD2
    eGenomeFANCD2
    euGene2177
    Genomic and cartography
    GoldenPathFANCD2  -     chr3:10043113-10118614 +  3p25.3   [Description]    (hg18-Mar_2006)
    EnsemblFANCD2 - 3p25.3 [CytoView]
    NCBIMapview
    OMIMDisease map [OMIM]
    HomoloGeneFANCD2
    Gene and transcription
    GenbankAF230336 [ ENTREZ ]
    GenbankAF340183 [ ENTREZ ]
    GenbankAK022613 [ ENTREZ ]
    GenbankAK074406 [ ENTREZ ]
    GenbankAK307512 [ ENTREZ ]
    RefSeqNM_001018115 [ SRS ]    NM_001018115 [ ENTREZ ]
    RefSeqNM_033084 [ SRS ]    NM_033084 [ ENTREZ ]
    RefSeqAC_000046 [ SRS ]    AC_000046 [ ENTREZ ]
    RefSeqAC_000135 [ SRS ]    AC_000135 [ ENTREZ ]
    RefSeqNC_000003 [ SRS ]    NC_000003 [ ENTREZ ]
    RefSeqNG_007311 [ SRS ]    NG_007311 [ ENTREZ ]
    RefSeqNT_022517 [ SRS ]    NT_022517 [ ENTREZ ]
    RefSeqNW_001838876 [ SRS ]    NW_001838876 [ ENTREZ ]
    RefSeqNW_921651 [ SRS ]    NW_921651 [ ENTREZ ]
    AceViewFANCD2 AceView - NCBI
    UnigeneHs.208388 [ SRS ]    Hs.208388 [ NCBI ]     HS208388 [ spliceNest ]
    Fast-db1833 (alternative variants)
    Protein : pattern, domain, 3D structure
    SwissProtQ9BXW9 [ SRS]    Q9BXW9 [ EXPASY ]     Q9BXW9 [ INTERPRO ]     Q9BXW9 [ UNIPROT ]
    CluSTrQ9BXW9
    BlocksQ9BXW9
    HPRD01968
    Protein Interaction databases
    DIPQ9BXW9
    IntActQ9BXW9
    Polymorphism : SNP, mutations, diseases
    OMIM227646    [ map ]   
    GENECLINICS227646
    SNPFANCD2 [dbSNP-NCBI]  
    SNPNM_001018115 [SNP-NCI]  
    SNPNM_033084 [SNP-NCI]  
    SNPFANCD2 [GeneSNPs - Utah]  FANCD2] [HGBASE - SRS]
    HAPMAPFANCD2 [HAPMAP]  
    COSMICFANCD2 [Somatic mutation (COSMIC-CGP-Sanger)]  
    HGMDFANCD2
    General knowledge
    Family BrowserFANCD2 [UCSC Family Browser]
    SOURCENM_001018115
    SOURCENM_033084
    SMDHs.208388
    SAGEHs.208388
    GOmolecular_function [Amigo]  molecular_function
    GOprotein binding [Amigo]  protein binding
    GOcellular_component [Amigo]  cellular_component
    GOnucleus [Amigo]  nucleus
    GOchromosome [Amigo]  chromosome
    GODNA repair [Amigo]  DNA repair
    GOcell cycle [Amigo]  cell cycle
    GObiological_process [Amigo]  biological_process
    GOresponse to gamma radiation [Amigo]  response to gamma radiation
    BIOCARTARole of BRCA1, BRCA2 and ATR in Cancer Susceptibility    [Genes]
    BIOCARTABRCA1-dependent Ub-ligase activity    [Genes]
    PubGeneFANCD2
    TreeFamFANCD2
    CTD2177 [Comparative ToxicoGenomics Database]
    Other databases
    Other databaseFanconi anemia mutation database
    Probes
    ProbeCancer Cytogenetics (Bari)
    ProbeFANCD2 Related clones (RZPD - Berlin)
    PubMed
    PubMed54 Pubmed reference(s) in Entrez

    Bibliography

    Microcell mediated chromosome transfer maps the Fanconi anaemia group D gene to chromosome 3p.
    Whitney M, Thayer M, Reifsteck C, Olson S, Smith L, Jakobs PM, Leach R, Naylor S, Joenje H, Grompe M
    Nature genetics. 1995 ; 11 (3) : 341-343.
    PMID 7581463
     
    Molecular biology of Fanconi anemia: implications for diagnosis and therapy.
    D'Andrea AD, Grompe M
    Blood. 1997 ; 90 (5) : 1725-1736.
    PMID 9292505
     
    Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex.
    Garcia-Higuera I, Kuang Y, Nˆ§f D, Wasik J, D'Andrea AD
    Molecular and cellular biology. 1999 ; 19 (7) : 4866-4873.
    PMID 10373536
     
    Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group.
    Faivre L, Guardiola P, Lewis C, Dokal I, Ebell W, Zatterale A, Altay C, Poole J, Stones D, Kwee ML, van Weel-Sipman M, Havenga C, Morgan N, de Winter J, Digweed M, Savoia A, Pronk J, de Ravel T, Jansen S, Joenje H, Gluckman E, Mathew CG
    Blood. 2000 ; 96 (13) : 4064-4070.
    PMID 11110674
     
    Localization of the Fanconi anemia complementation group D gene to a 200-kb region on chromosome 3p25.3.
    Hejna JA, Timmers CD, Reifsteck C, Bruun DA, Lucas LW, Jakobs PM, Toth-Fejel S, Unsworth N, Clemens SL, Garcia DK, Naylor SL, Thayer MJ, Olson SB, Grompe M, Moses RE
    American journal of human genetics. 2000 ; 66 (5) : 1540-1551.
    PMID 10762542
     
    Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.
    Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD
    Molecular cell. 2001 ; 7 (2) : 249-262.
    PMID 11239454
     
    Fanconi anemia and DNA repair.
    Grompe M, D'Andrea A
    Human molecular genetics. 2001 ; 10 (20) : 2253-2259.
    PMID 11673408
     
    Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway.
    Medhurst AL, Huber PA, Waisfisz Q, de Winter JP, Mathew CG
    Human molecular genetics. 2001 ; 10 (4) : 423-429.
    PMID 11157805
     
    Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner.
    Qiao F, Moss A, Kupfer GM
    The Journal of biological chemistry. 2001 ; 276 (26) : 23391-23396.
    PMID 11297559
     
    Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9.
    Yang Y, Kuang Y, Montes De Oca R, Hays T, Moreau L, Lu N, Seed B, D'Andrea AD
    Blood. 2001 ; 98 (12) : 3435-3440.
    PMID 11719385
     
    Positional cloning of a novel Fanconi anemia gene, FANCD2.
    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
    Molecular cell. 2001 ; 7 (2) : 241-248.
    PMID 11239453
     
    The Chinese hamster FANCG/XRCC9 mutant NM3 fails to express the monoubiquitinated form of the FANCD2 protein, is hypersensitive to a range of DNA damaging agents and exhibits a normal level of spontaneous sister chromatid exchange.
    Wilson JB, Johnson MA, Stuckert AP, Trueman KL, May S, Bryant PE, Meyn RE, D'Andrea AD, Jones NJ
    Carcinogenesis. 2001 ; 22 (12) : 1939-1946.
    PMID 11751423
     
    Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes.
    Yamashita T, Nakahata T
    International journal of hematology. 2001 ; 74 (1) : 33-41.
    PMID 11530803
     
    Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia.
    Callˆ©n E, Samper E, Ramˆ‚rez MJ, Creus A, Marcos R, Ortega JJ, Olivˆ© T, Badell I, Blasco MA, Surrallˆ©s J
    Human molecular genetics. 2002 ; 11 (4) : 439-444.
    PMID 11854176
     
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    Contributor(s)

    Written04-1998Jean-Loup Huret
    Updated06-2002Jean-Loup Huret

    Citation

    This paper should be referenced as such :
    Huret JL . FANCD2 (Fanconi anemia, complementation group D2). Atlas Genet Cytogenet Oncol Haematol. April 1998 .
    URL : http://AtlasGeneticsOncology.org/Genes/FAD.html
    Huret JL . FANCD2 (Fanconi anemia, complementation group D2). Atlas Genet Cytogenet Oncol Haematol. June 2002 .
    URL : http://AtlasGeneticsOncology.org/Genes/FAD.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Mon Sep 29 18:39:20 2008

    Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    j.l.huret@chu-poitiers.fr.