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FACC (Fanconi anaemia complementation group C)

Identity

Other namesFAC
HGNC FANCC
Location 9q22.3
Local_order next to PTCH and XPAC !!

DNA/RNA

Description 14 exons; spans 80 kb
Transcription mRNA of 2.3, 3.2, and 4.6 kb (alternative splicing in 5', variable 3' untranslated region, exon 13 skipping)

Protein

Description 558 amino acids; 63 kDa
Expression wide, in particular in the bones; high expression in proliferating cells, low in differentiated cells
Localisation cytoplasmic (mostly) and nuclear
Function
  • part of the FA complex with FANCA, 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, 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.
  • FANCC may have mutlifunctional roles, in addition to its involvement in the FA pathway. FANCC binds to cdc2 (mitotic cyclin-dependent kinase), STAT1, GRP94 (a chaperon protein), NADPH, and a number of other proteins; involved in DNA repair and in suppressing interferon gamma induced cellular apoptosis
    • Homology no known homology

    Mutations

    Germinal most mutations are found in exon1, intron 4, and exon 14

    Implicated in

    Entity Fanconi anaemia (FA); FACC is implicated in the FA complementation group C; it represents about 15% of FA cases
    Disease Fanconi anaemia is a chromosome instability syndrome/cancer prone disease (at risk of leukaemia)
    Prognosis
  • Fanconi anaemia's prognosis is poor; mean survival is 16 years: patients die of bone marrow failure (infections, haemorrhages), leukaemia, or androgen therapy related liver tumours
  • It has recently been shown that significant phenotypic differences were found between the various complementation groups. FA group C patients had less somatic abnormalities. However, there is a certain clinical heterogeneity.
    • Cytogenetics spontaneous,chromatid/chromosome breaks; increased rate of breaks compared to control, when induced by breaking agent
      

    External links

    Nomenclature
    HGNCFANCC   3584
    Entrez_GeneFANCC  2176  Fanconi anemia, complementation group C
    Cards
    AtlasFACC101
    GeneCardsFANCC
    EnsemblFANCC [Search_View]   ENSG00000158169 [Gene_View]
    GenatlasFANCC
    GeneLynxFANCC
    eGenomeFANCC
    euGene2176
    Genomic and cartography
    GoldenPathFANCC  -  9q22.3   chr9:96901157-97119812 -  9q22.3   [Description]    (hg18-Mar_2006)
    EnsemblFANCC - 9q22.3 [CytoView]
    NCBIMapview
    OMIMDisease map [OMIM]
    HomoloGeneFANCC
    Gene and transcription
    GenbankAK222871 [ ENTREZ ]
    GenbankAK310599 [ ENTREZ ]
    GenbankAK312548 [ ENTREZ ]
    GenbankAU132608 [ ENTREZ ]
    GenbankBC006303 [ ENTREZ ]
    RefSeqNM_000136 [ SRS ]    NM_000136 [ ENTREZ ]
    RefSeqAC_000052 [ SRS ]    AC_000052 [ ENTREZ ]
    RefSeqAC_000141 [ SRS ]    AC_000141 [ ENTREZ ]
    RefSeqNC_000009 [ SRS ]    NC_000009 [ ENTREZ ]
    RefSeqNT_008470 [ SRS ]    NT_008470 [ ENTREZ ]
    RefSeqNW_001839235 [ SRS ]    NW_001839235 [ ENTREZ ]
    RefSeqNW_924506 [ SRS ]    NW_924506 [ ENTREZ ]
    AceViewFANCC AceView - NCBI
    UnigeneHs.494529 [ SRS ]    Hs.494529 [ NCBI ]     HS494529 [ spliceNest ]
    Fast-db11246 (alternative variants)
    Protein : pattern, domain, 3D structure
    SwissProtQ00597 [ SRS]    Q00597 [ EXPASY ]     Q00597 [ INTERPRO ]     Q00597 [ UNIPROT ]
    InterproIPR000686 Fanconi [ SRS ]    IPR000686 Fanconi [ EBI ]
    CluSTrQ00597
    PfamPF02106 Fanconi_C [ SRS ]    PF02106 Fanconi_C [ Sanger ]    pfam02106 [ NCBI-CDD ]
    BlocksQ00597
    HPRD01967
    Protein Interaction databases
    DIPQ00597
    IntActQ00597
    Polymorphism : SNP, mutations, diseases
    OMIM227645    [ map ]   
    GENECLINICS227645
    SNPFANCC [dbSNP-NCBI]  
    SNPNM_000136 [SNP-NCI]  
    SNPFANCC [GeneSNPs - Utah]  FANCC] [HGBASE - SRS]
    HAPMAPFANCC [HAPMAP]  
    COSMICFANCC [Somatic mutation (COSMIC-CGP-Sanger)]  
    HGMDFANCC
    General knowledge
    Family BrowserFANCC [UCSC Family Browser]
    SOURCENM_000136
    SMDHs.494529
    SAGEHs.494529
    GOprotein binding [Amigo]  protein binding
    GOnucleus [Amigo]  nucleus
    GOcytoplasm [Amigo]  cytoplasm
    GOcytosol [Amigo]  cytosol
    GODNA repair [Amigo]  DNA repair
    GOprotein complex assembly [Amigo]  protein complex assembly
    BIOCARTARole of BRCA1, BRCA2 and ATR in Cancer Susceptibility    [Genes]
    BIOCARTABRCA1-dependent Ub-ligase activity    [Genes]
    PubGeneFANCC
    TreeFamFANCC
    CTD2176 [Comparative ToxicoGenomics Database]
    Other databases
    Other databaseFanconi Anemia Mutation Database
    Probes
    ProbeCancer Cytogenetics (Bari)
    ProbeFANCC Related clones (RZPD - Berlin)
    PubMed
    PubMed72 Pubmed reference(s) in LocusLink

    Bibliography

    Cloning of cDNAs for Fanconi's anaemia by functional complementation.
    Strathdee CA, Gavish H, Shannon WR, Buchwald M
    Nature. 1992 ; 356 (6372) : 763-767.
    PMID 1574115
     
    Characterisation of the exon structure of the Fanconi anaemia group C gene by vectorette PCR.
    Gibson RA, Buchwald M, Roberts RG, Mathew CG
    Human molecular genetics. 1993 ; 2 (1) : 35-38.
    PMID 8490620
     
    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
     
    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
     
    The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality.
    Pang Q, Christianson TA, Keeble W, Diaz J, Faulkner GR, Reifsteck C, Olson S, Bagby GC
    Blood. 2001 ; 98 (5) : 1392-1401.
    PMID 11520787
     
    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
     
    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

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    Contributor(s)

    Written02-1998Jean-Loup Huret
    Updated06-2002Jean-Loup Huret

    Citation

    This paper should be referenced as such :
    Huret JL . FACC (Fanconi anaemia complementation group C). Atlas Genet Cytogenet Oncol Haematol. February 1998 .
    URL : http://AtlasGeneticsOncology.org/Genes/FACC101.html
    Huret JL . FACC (Fanconi anaemia complementation group C). Atlas Genet Cytogenet Oncol Haematol. June 2002 .
    URL : http://AtlasGeneticsOncology.org/Genes/FACC101.html

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    indexed on : Mon Aug 11 21:13:47 2008

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