Recombinant Human SAMHD1 protein (GST tag N-Terminus)

一般的な情報

機能

Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks (PubMed : 19525956, PubMed : 21613998, PubMed : 21720370, PubMed : 22056990, PubMed : 23601106, PubMed : 23602554, PubMed : 24336198, PubMed : 26294762, PubMed : 26431200, PubMed : 28229507, PubMed : 28834754, PubMed : 29670289). Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses, such as HIV-1 : dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells (PubMed : 19525956, PubMed : 21613998, PubMed : 21720370, PubMed : 22056990, PubMed : 23364794, PubMed : 23601106, PubMed : 23602554, PubMed : 24336198, PubMed : 25038827, PubMed : 26101257, PubMed : 26294762, PubMed : 26431200, PubMed : 28229507). Likewise, suppresses LINE-1 retrotransposon activity (PubMed : 24035396, PubMed : 24217394, PubMed : 29610582). Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx (PubMed : 21613998, PubMed : 21720370). In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools (PubMed : 23858451). Phosphorylation at Thr-592 acts as a switch to control dNTPase-dependent and -independent functions : it inhibits dNTPase activity and ability to restrict infection by viruses, while it promotes DNA end resection at stalled replication forks (PubMed : 23601106, PubMed : 23602554, PubMed : 29610582, PubMed : 29670289). Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks : acts by stimulating the exonuclease activity of MRE11, activating the ATR-CHK1 pathway and allowing the forks to restart replication (PubMed : 29670289). Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation (PubMed : 27477283, PubMed : 29670289). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (PubMed : 29670289). Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity).

配列の類似性

Belongs to the SAMHD1 family.

翻訳後修飾

Phosphorylation at Thr-592 by CDK1 acts as a switch to control deoxynucleoside triphosphate (dNTPase)-dependent and -independent functions (PubMed:29670289). Phosphorylation at Thr-592 takes place in cycling cells: it reduces the stability of the homotetramer, impairing the dNTPase activity and subsequent ability to restrict infection by viruses (PubMed:23601106, PubMed:23602554, PubMed:26294762, PubMed:26431200, PubMed:31291580). It also inhibits ability to suppress LINE-1 retrotransposon activity (PubMed:29610582). In contrast, phosphorylation at Thr-592 promotes DNA end resection at stalled replication forks in response to DNA damage (PubMed:29670289).. (Microbial infection) Phosphorylation at Thr-592 by Epstein-Barr virus kinase BGLF4 and human cytomegalovirus/HCMV UL97 leads to a reduced level of dCTPase and dTTPase activity and the loss of viral restriction.. (Microbial infection) Ubiquitinated following interaction with HIV-2 viral protein Vpx; Vpx promotes interaction and with a DCX (DDB1-CUL4-X-box) E3 ubiquitin ligase, leading to proteasomal degradation.