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FACC (Fanconi anaemia complementation group C)

Identity

Other namesFAC
HGNC (Hugo) FANCC
Location 9q22.3
Location_base_pair Starts at 96901157 and ends at 97119812 bp from pter ( according to hg18-Mar_2006)  [Mapping]
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
    HGNC (Hugo)FANCC   3584
    Entrez_Gene (NCBI)FANCC  2176  Fanconi anemia, complementation group C
    Cards
    AtlasFACC101
    GeneCards (Weizmann)FANCC
    Ensembl (Hinxton)ENSG00000158169 [Gene_View]  FANCC [Vega]
    AceView (NCBI)FANCC
    Genatlas (Paris)FANCC
    euGene (Indiana)2176
    SOURCE (Stanford)NM_000136
    Genomic and cartography
    GoldenPath (UCSC)FANCC  -  9q22.3   chr9:96901157-97119812 -  9q22.3   [Description]    (hg18-Mar_2006)
    EnsemblFANCC - 9q22.3 [CytoView]
    Mapping of homologs : NCBIFANCC [Mapview]
    OMIM227645   
    Gene and transcription
    Gene : Genbank (Entrez)AK222871 AK304887 AK310599 AK312548 AU132608
    Reference sequence (RefSeq transcript) :SRSNM_000136
    Reference transcript : EntrezNM_000136
    RefSeq genomic : SRSAC_000052 AC_000141 NC_000009 NT_008470 NW_001839235 NW_924506
    RefSeq genomic : EntrezAC_000052 AC_000141 NC_000009 NT_008470 NW_001839235 NW_924506
    Consensus coding sequences : CCDS NCBIFANCC
    Cluster EST : UnigeneHs.494529 [ SRS ] Hs.494529 [ NCBI ]
    Alternative Splicing : Fast-db (Paris)11246
    Protein : pattern, domain, 3D structure
    Protein : UniProt/SwissProtQ00597 (SRS) Q00597 (Expasy) Q00597 (Uniprot)
    With graphics : InterProQ00597
    Splice isoforms : VarSplice FASTAQ00597(VarSplice FASTA)
    Domains : Interpro (SRS)Fanconi   
    Domains : Interpro (EBI)Fanconi   
    Related proteins : CluSTrQ00597
    Domain families : Pfam SRSFanconi_C (PF02106)   
    Domain families : Pfam SangerFanconi_C (PF02106)   
    Domain families : Pfam NCBIpfam02106   
    Blocks (Seattle)Q00597
    Crystal structure of protein : PDB SRS
    Crystal structure of protein : PDBSum
    Crystal structure of protein : IMB
    Crystal structure of protein : PDB RSDB
    HPRD01967
    Protein Interaction databases
    DIP (DOE-UCLA)Q00597
    IntAct (EBI)Q00597
    Polymorphism : SNP, mutations, diseases
    Single Nucleotide Polymorphism (SNP) : dbSNP NCBIFANCC
    SNP : GeneSNP UtahFANCC
    SNP : HGBaseFANCC
    Genetic variants : HAPMAPFANCC
    Somatic Mutations in Cancer : COSMICFANCC 
    Mutations and Diseases : HGMDFANCC
    Hereditary diseases : OMIM227645   
    Hereditary diseases : GENETests227645   
    Diseases : Genetic AssociationFANCC
    General knowledge
    Homologs : HomoloGeneFANCC
    Homology/Alignments : Family Browser UCSCFANCC
    Phylogenetic Trees/Animal Genes : TreeFamFANCC
    Chemical/Protein Interactions : CTD2176
    Keywords Ontology : AmiGOprotein binding  nucleus  cytoplasm  cytosol  DNA repair  protein complex assembly  response to DNA damage stimulus  
    Keywords Ontology : EGO-EBIprotein binding  nucleus  cytoplasm  cytosol  DNA repair  protein complex assembly  response to DNA damage stimulus  
    Pathways : BIOCARTARole of BRCA1, BRCA2 and ATR in Cancer Susceptibility [Genes]    BRCA1-dependent Ub-ligase activity [Genes]   
    Pathways : KEGG
    Other databases
    Other databaseFanconi Anemia Mutation Database
    Probes
    ProbeCancer Cytogenetics (Bari)
    Probes : ImagenesFANCC Related clones (RZPD - Berlin)
    Literature
    PubMed75 Pubmed reference(s) in Entrez
    PubGeneFANCC

    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
     
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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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