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FANCD2/FANCI-associated nuclease 1 (KIAA1018) is an enzyme that in humans is encoded by the FAN1 gene. It is a structure dependent endonuclease and a member of the myotubularin-related class 1 cysteine-based protein tyrosine phosphatases. It is thought to play an important role in the Fanconi Anemia (FA) pathway. == Structure == FAN1 is a protein of 1017 amino acids. Several crystal structures of the residues 373-1017 have been characterized. This portion of FAN1 contains three domains: an SAP domain (primary-DNA binding domain), a TPR domain (mediating interdomain interaction and dimerization interface) and the virus-type replication-repair nuclease module (VRR_NUC, catalytic cite) (Figure 1). DNA binding promotes dimerization of FAN1 in a "head to tail" fashion. The SAP region contains three major components: α9, α5β1, and α7. The core helix α9 stabilizes the protein as it moves through dimer configurations and mediates the interactions between α5β1 and α7 as they adjust their positions. These three configurations are the substrate scanning, substrate latching and substrate unwinding forms (figure 2).〔 In the FAN1 dimer, the SAP regions of both FAN1 enzymes make contact with the DNA duplex (dsDNA). This double contact facilitates DNA induced dimerization, as well as guiding the single stranded (ssDNA) into the SAP domain of the downstream enzyme (PSAP). The SAP domain of the upstream FAN1 component enzyme (ASAP) aids in guiding the DNA to PSAP.〔 The SAP surface facing the catalytic site is the most conserved region between FAN1 homologs. It is positively charged for favorable hydrogen bonding and electrostatic interactions with DNA. In particular, residues Y374 and Y436 form hydrogen bonds with the phosphate backbone. FAN1 can bind DNA in either direction. However, when the 5' flab is facing away from the VRR_NUC site, substrate latching and unwinding cannot occur.〔 The unresolved portion of FAN1 contains a Zinc finger at the N terminus called a UBZ region. This is present in proteins that bind to ubiquitinated proteins, and is highly conserved across eukaryotes. This Zinc finger is crucial for recruitment to the ubiquitinated FANCD2/FANCI complex, and is found in other nucleases.〔 The VRR_Nuc catalytic domain is located at the C terminus and contains the endonuclease functionality.〔 FAN1 is the first known instance of a virus type replication-repair nuclease module in eukaryotes. It is normally found as a standalone domain in bacterial and viral Holliday Junction Resolvases (HJR). FAN1 does not exhibit any activity on Holliday Junction (HJ) substrates.〔 A subdomain of SAP consisting of six α helices connected to the VRR_Nuc region is thought to inhibit HJR activity. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「FAN1」の詳細全文を読む スポンサード リンク
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