Discovery and nomenclature
The partial-length cDNA of C17orf70 was first cloned, sequenced and deposited by the RIKEN Yokohama Institute, Protein Research Group (LOC80233). The full-length cDNA was subsequently isolated (DQ989324) [1]. The gene corresponding to LOC80233 cDNA was named C17orf70 suggesting it is a putative ORF number 70 located on chromosome 17. The protein encoded by C17orf70 was first identified as a component of the Fanconi anemia nuclear core complex [2]. The protein was named as FAAP100 (FANCA-associated polypeptide of 100 kDa mass) [1].
Structure
- The full length FAAP100 protein is 881 amino acids long with a predicted molecular weight of 933.4 kDa [1].
- FAAP100 had an apparent apparent molecular mass of 100 kDa by SDS-PAGE [1].
- FAAP100 contains putative coiled-coil domain [1].
Orthologs
- FAAP100 protein is conserved only in vertebrates but not in invertebrates and yeast [1].
Interactions
- FAAP100 interact with FANCB and FANCL and forms a subcomplex [1].
- Using mammalian two-hybrid assay, it was shown that FAAP100 interact directly with FANCB [1].
- Using mammalian three-hybrid assay it was shown that FAAP100 form a subcomplex with FANCB and FANCL through direct interaction [1].
- Biochemical purification of FANCL from cytosol and nuclear extracts of HeLa cells revealed the presence of FANCB and FAAP100 polypeptides in the purified complex in roughly stoichiometric levels [1].
- FAAP100 is an integral component of the FA core complex [1].
- FAAP100 was co-immunoprecipitated by antibodies against multiple core complex components, including FANCA and FANCB [1].
- Immunoprecipitation with the FAAP100 antibody obtained several members of the core complex tested, including FANCA, FANCB, FANCL, and FANCM [1].
- Gel filtration profile of FAAP100 is coincidental with that of FANCL suggesting that these proteins are predominantly present in the same subcomplex(es) [1].
Function
- FAAP100 is essential for the monoubiquitination of FANCD2 [1].
- FAAP100 depleted cells using siRNA display reduced levels of monoubiquitinated FANCD2 in the absence and presence of DNA-damaging agents such as mitomycin c (MMC), cisplatin, and hydroxyurea [1].
- FAAP100 is essential for the stability of the FA core complex [1].
- Depletion of FAAP100 in HeLa cells usiing siRNA results in the reduced levels of FANCB, FANCL, FANCA and FANCG [1]
References
