FANCA (FACA)

FANCA is one of the six known Fanconi anemia gene products (FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG proteins). Fanconi anemia (FA) is a genetic disorder predisposing to aplastic anemia and cancer characterized by hypersensitivity to DNA-damaging agents and oxidative stress. FANCA associates with the IκB kinase (IKK) signalsome via interaction with IKK2. Components of the FANCA complex undergo rapid, stimulus-dependent changes in phosphorylation, which are blocked by kinase-inactive IKK2. When exposed to mitomycin C, cells expressing IKK2 develop a cell cycle abnormality characteristic of FA. Thus, FANCA may function to recruit IKK2, thus providing the cell a means of rapidly responding to stress.

FANCA (FACA) Related Areas

 

FANCA (FACA) Alternative Names

FA, FA-H, FA1, FAA, FACA, FAH, FANCH, MGC75158[Homo sapiens]

AW208693, FACA[Mus musculus]

Summaries for FANCA (FACA)

Entrez Gene summary for FANCA:

The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic 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 A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this FANCA gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]

OMIM - description for FANCA:

Soulier et al. (2005) noted that the FANCA, -C (613899), -E (613976), -F (613897), -G (602956), and -L (608111) proteins are part of a nuclear multiprotein core complex which triggers activating monoubiquitination of the FANCD2 (613984) protein during S phase of the growth cycle and after exposure to DNA crosslinking agents. The FA/BRCA pathway is involved in the repair of DNA damage. FANCM (609644) is also part of the FA core complex (Meetei et al., 2005).

Wikipedia summary for FANCA:

Fanconi anemia, complementation group A, also known as FANCA, is a protein which in humans is encoded by the FANCA gene.

Human FANCA (FACA) Protein General Information

 

• Protein names: Fanconi anemia group A protein, Short name=Protein FACA
• Sequence length: 1455 AA.
• Post-translational modification: Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylation is required for the formation of the nuclear complex. Not phosphorylated in cells derived from groups A, B, C, E, F, G, and H.
• Subunit structure: FANCA belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. The complex is not found in FA patients. In complex with FANCF, FANCG and FANCL, but not with FANCC, nor FANCE, interacts with HES1; this interaction may be essential for the stability and nuclear localization of FA core complex proteins. The complex with FANCC and FANCG may also include EIF2AK2 and HSP70.
• Subcellular location: Nucleus. Cytoplasm. Note: The major form is nuclear. The minor form is cytoplasmic.
• Involvement in disease: Defects in FANCA are a cause of Fanconi anemia (FA) [MIM:227650]. FA is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.

General information above from UniProt

Function for FANCA (FACA) Protein

UniProtKB:

FANCA is DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. FANCA may be involved in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability.

Genatlas:

• FANCA is involved in genomic stability and control of apoptosis
• FANCA is involved in blunt DNA ends joining
• FANCA is the protection of the genomic integrity of cells
• FANCA is required to prevent accumulation of replication-associated DNA double-strand breaks
• FANCA is nucleocytoplasmic shuttling molecule required for gonadotropin-releasing hormone (GNRH1) transduction of the GnRH receptor (GNRHR)
• member of the Group I Fanconi anemia proteins including also FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL

Homology for human FANCA (FACA)

• homolog to murine Fanca

Phenotype Information for FANCA (FACA)

• Gene/Locus: FANCA, FACA, FA1, FA, FAA
• Phenotype: Fanconi anemia, complementation group A

Phenotype Information for FANCA from OMIM (Online Mendelian Inheritance in Man)