FANCA
In databases:
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery):
2175 or FANCA
Ensembl (http://www.ensembl.org/index.html):
ENSG00000187741
UniProt (http://www.uniprot.org/): O15360
OMIM (http://www.ncbi.nlm.nih.gov/omim):
607139
GeneCards (http://www.genecards.org/): FANCA
HGNC (http://www.genenames.org/): 3582 or FANCA
Gene locus:
16q24.3
Protein name:
Fanconi anemia, complementation group A
Protein Size:
1455 amino acids; about 163 kDa
FANCB
In
databases:
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 2187 or FANCB
Ensembl (http://www.ensembl.org/index.html):
ENSG00000181544
UniProt (http://www.uniprot.org/):
Q8NB91
OMIM (http://www.ncbi.nlm.nih.gov/omim):
300515
GeneCards (http://www.genecards.org/): FANCB
HGNC (http://www.genenames.org/): 3583 or FANCB
Gene locus:
Xp22.2
Protein name:
Fanconi anemia, complementation group B
Protein Size:
859 amino acids; about 98 kDa
FANCC
In databases:
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery):
2176 or FANCC
Ensembl (http://www.ensembl.org/index.html):
ENSG00000158169
UniProt (http://www.uniprot.org/):
Q00597
OMIM (http://www.ncbi.nlm.nih.gov/omim):
227645
GeneCards (http://www.genecards.org/): FANCC
HGNC (http://www.genenames.org/): 3584 or FANCC
Gene locus:
9q22.3
Protein name:
Fanconi anemia, complementation group C
Protein Size:
558 amino acids; about 63 kDa
BRCA2 (FANCD1)
In
databases :
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery):
675 or BRCA2
Ensembl (http://www.ensembl.org/index.html):
ENSG00000139618
GeneCards (http://www.genecards.org/): BRCA2
HGNC (http://www.genenames.org/): 1101 or BRCA2
Gene locus:
13q12-q13
Protein name:
Breast cancer 2, early onset
Protein Size:
3418 amino acids; about 384 kDa
FANCD2
In
databases :
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery):
2177 or FANCD2
Ensembl (http://www.ensembl.org/index.html):
ENSG00000144554
UniProt (http://www.uniprot.org/):
Q9BXW9
OMIM (http://www.ncbi.nlm.nih.gov/omim):
227646
GeneCards (http://www.genecards.org/): FANCD2
HGNC (http://www.genenames.org/): 3585 or FANCD2
Gene locus:
3p25.3
Protein name:
Fanconi anemia, complementation group D2
Protein Size:
1471 amino acids; about 166 kDa
FANCE
In
databases :
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery):
2178 or FANCE
Ensembl (http://www.ensembl.org/index.html):
ENSG00000112039
HGNC (http://www.genenames.org/): 3586 or FANCE
Gene locus :
6p21-22
Protein name:
Fanconi anemia, complementation group E
Protein Size:
536 amino acids; about 59 kDa
FANCF
In
databases :
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 2188 or FANCF
Ensembl (http://www.ensembl.org/index.html):
ENSG00000183161
UniProt (http://www.uniprot.org/):
Q9NPI8
OMIM (http://www.ncbi.nlm.nih.gov/omim):
603467
HGNC (http://www.genenames.org/): 3587 or FANCF
Gene locus
11p15
Protein name:
Fanconi anemia, complementation group F
Protein Size:
374 amino acids; about 42 kDa
FANCG
In
databases :
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 2189 or FANCG
Ensembl (http://www.ensembl.org/index.html):
ENSG00000165281
UniProt (http://www.uniprot.org/): O15287
OMIM (http://www.ncbi.nlm.nih.gov/omim):
602956
GeneCards (http://www.genecards.org/): FANCG
HGNC (http://www.genenames.org/): 3588 or FANCG
Gene locus:
9p13
Protein name:
Fanconi anemia, complementation group G
Protein Size:
622 amino acids; about 69 kDa
FANCI
In
databases :
Ensembl (http://www.ensembl.org/index.html):
ENSG00000140525
UniProt (http://www.uniprot.org/):
Q9NVI1
OMIM (http://www.ncbi.nlm.nih.gov/omim):
607139
HGNC (http://www.genenames.org/): 25568 or FANCI
Gene
locus :
15q26.1
Protein name:
Fanconi anemia, complementation group I
Protein Size:
1328 amino acids; about 149 kDa
BRIP1 (alias FANCJ)
In
databases :
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery):
83990 or BRIP1
Ensembl (http://www.ensembl.org/index.html):
ENSG00000136492
UniProt (http://www.uniprot.org/):
Q9BX63
OMIM (http://www.ncbi.nlm.nih.gov/omim):
609054
HGNC (http://www.genenames.org/): 20473 or BRIP1
Gene locus:
17q23.2
Protein name:
BRCA1 interacting protein C-terminal
helicase 1 (BRIP1) or Fanconi anemia, complementation group J (FANCJ)
Protein Size:
1249 amino acids; about 141 Da
FANCL
In
databases :
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery):
55120 or FANCL
GeneCards (http://www.genecards.org/): FANCL
HGNC (http://www.genenames.org/): 20748 or FANCL
EC number : EC
6.3.2.
Gene locus:
2p16.1
Protein name:
Fanconi anemia, complementation group L
Protein Size:
375 amino acids; about 43 kDa
FANCM
In
databases :
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 57697 or FANCM
Ensembl (http://www.ensembl.org/index.html):
ENSG00000187790
UniProt (http://www.uniprot.org/):
Q8IYD8
OMIM (http://www.ncbi.nlm.nih.gov/omim):
609644
GeneCards (http://www.genecards.org/): FANCM
HGNC (http://www.genenames.org/): 23168 or FANCM
EC number : EC
3.6.1
Gene locus:
14q21.2
Protein name:
Fanconi anemia, complementation group M
Protein Size:
2048 amino acids; about 232 kDa
PALB2 (alias FANCN)
In
databases :
Ensembl (http://www.ensembl.org/index.html):
ENSG00000083093
UniProt (http://www.uniprot.org/):
Q86YC2
OMIM (http://www.ncbi.nlm.nih.gov/omim):
610355
HGNC (http://www.genenames.org/): 26144 or PALB2
Gene
locus :
16p12.2
Protein name:
Partner and localizer of BRCA2
Protein Size:
1186 amino acids; about 131 kDa
RAD51C (alias FANCO)
In
databases :
Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery):
5889 or RAD51C
Ensembl (http://www.ensembl.org/index.html):
ENSG00000108384
UniProt (http://www.uniprot.org/): O43502
OMIM (http://www.ncbi.nlm.nih.gov/omim):
602774
GeneCards (http://www.genecards.org/): RAD51C
HGNC (http://www.genenames.org/): 9820 or RAD51C
Gene locus:
17q25.1
Protein name:
RAD51 homolog C (S. cerevisiae)
Protein Size:
376 amino acids; about 42 kDa
Function:
The proteins encoded by the genes
presented here are believed to function in a common DNA
repair signaling pathway, the Fanconi
Anemia (FA) pathway, which closely cooperates with other DNA repair proteins
for resolving DNA interstrand cross-links (ICLs) during DNA replication. ICLs
are among the most deleterious DNA lesions, since they block DNA replication
and transcription. DNA ICLs can be caused by endogenous sources such as nitrous
acid and aldehydes, or exogenous agents such as cisplatin and its derivatives.
A central event in the resolution of DNA
ICLs is the monoubiquitination of FANCD2 and
FANCI upon DNA damage, which is mediated
by a group of upstream FA proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG,
FANCL, and FANCM) that are assembled into a large nuclear E3 ubiquitin ligase complex,
termed the ‘‘FA core complex’’ (Kennedy and D’Andrea 2005; Wang 2007).
The monoubiquitinated FANCD2/FANCI
heterodimer was shown to play multiple roles in the pathway (Knipscheer et al.
2009), and to functionally interact with downstream FA proteins such as FANCD1
(or BRCA2), FANCN (or PALB2), and FANCJ (or BRIP1), and their associated
proteins, BRCA1 or RAD51C.
Cancer-related alterations:
FA is a genetically heterogeneous,
autosomal recessive disorder characterized by bone marrow failure,
developmental abnormalities, and increased incidence of cancers. At the
cellular level, FA cells display increased chromosomal aberrations,
particularly radials, and hypersensitivity to DNA interstrand cross-link (ICL)
agents.
FA is caused by mutations in at least 13
distinct genes (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG,
FANCI, FANCJ, FANCL, FANCM, and FANCN). About 66% of FA cases are caused by
mutations in FANCA, 10% by mutations in FANCC and 10% by mutations in FANCG.
In FA genes, various germinal alterations
(nucleotide substitutions, deletions, or insertions) have been described.
Somatic point mutations are rare.
Principal cancers observed in biallelic mutation
carriers (phenotype of FA patients) are acute myeloid leukemia (AML), head and
neck squamous cell carcinoma (SCC), anogenital tumors. In the case of biallelic
mutation in FANCD1/BRCA2 or FANCN/PALB2, aggressive FA may be observed,
associated to childhood solid tumors (Wilms tumor and medulloblastoma).
In carriers of monoallelic mutation, only those with
alteration in FANCD1/BRCA2 are highly susceptible to (breast) cancer, while
carriers of FANCJ/BRIP1 or FANCN/PALB2 have a low-risk of developing breast
cancer.
References (open access):
Expanded roles of the Fanconi anemia pathway in
preserving genomic stability. Kee Y, D'Andrea AD. Genes Dev. 2010 Aug
15;24(16):1680-94.
Mutational analysis of FANCL, FANCM and the recently
identified FANCI suggests that among the 13 known Fanconi Anemia genes, only
FANCD1/BRCA2 plays a major role in high-risk breast cancer predisposition. García
MJ, Fernández V, Osorio A, Barroso A, Fernández F, Urioste M, Benítez J.
Carcinogenesis. 2009 Nov;30(11):1898-902.
RAD51C: a novel cancer susceptibility gene is linked
to Fanconi anemia and breast cancer. Somyajit K, Subramanya S, Nagaraju G. Carcinogenesis.
2010 Dec;31(12):2031-8.
Susceptibility pathways in Fanconi's anemia and breast
cancer. D'Andrea AD. N Engl J Med. 2010 May 20;362(20):1909-19.
Mutagenic repair of DNA interstrand crosslinks. Shen X, Li L. Environ Mol Mutagen. 2010 Jul;51(6):493-9.
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