EC Number   |
General Information |
Reference |
|---|
   3.1.5.B1 | metabolism |
SAMHD1 and R451A/L453A mutant proteins are degraded by virion-associated protein Vpx from HIV-2 but are not spontaneously ubiquitinated in the absence of Vpx. Their protein levels are enhanced only when both proteasomal and autophagy degradation pathways are inhibited |
751428 |
| 3.1.5.B1 | physiological function |
allosteric dGTP binding induces conformational changes at the active site, allowing a more stable interaction with the substrate and explaining the dGTP-induced dNTPase activity. Mutations of dGTP binding residues in the allosteric site affect tetramer formation, dNTPase activity and HIV-1 restriction. dGTP-triggered tetramer formation is also important for SAMHD1-mediated retrotransposition of LINE-1 elements |
730446 |
| 3.1.5.B1 | physiological function |
in the mouse, SAMHD1 is expressed as isoforms ISF1 and ISF2 that differ at the carboxyl terminus due to alternative splicing of the last coding exon. Both isoforms are antiviral in nondividing cells. Phosphomimetic mutation at Thr-634 of ISF1 ablates its antiviral activity but has little effect on phosphohydrolase activity in vitro. dGTP causes ISF1 to tetramerize, activating its catalytic activity. Isoform ISF2 lacks the phosphorylation site, is significantly more active, tetramerizes, and is active without added dGTP. Mouse SAMHD1 does not degrade HIV-1 genomic viral RNA |
751090 |
| 3.1.5.B1 | physiological function |
S-phase kinase CDK2-cyclin A phosphorylates SAMHD1 at residue Thr-592. Thr-592 phosphorylation occurs first at the G1/S border and is removed during mitotic exit. Thr-592 phosphorylation does not cause rapid protein degradation. SAMHD1 influences the size of the four dNTP pools independently of its phosphorylation |
750263 |
| 3.1.5.B1 | physiological function |
SAMHD1 also acts as a nuclease, specifically degrading retroviral genomic RNA in monocyte-derived macrophage-like cells and in primary monocyte-derived macrophages. SAMHD1 selectively restricts retroviral replication, but does not affect the replication of other common non-retro RNA genome viruses |
752156 |
| 3.1.5.B1 | physiological function |
the monomer and apo- or GTP-bound dimer of SAMHD1 are catalytically inactive. Binding of dNTP at allosteric site 2 (AS2), adjacent to the GTP-binding, allosteric site 1 (AS1), induces formation of tetramer, the catalytically active form. The apparent Km values of dNTPs at AS2 vary, in increasing order of dCTP, dGTP, dATP, dTTP. dCTP binding at AS2 significantly reduces the dCTP hydrolysis rate, which is restored to a rate comparable to that of other dNTPs upon dGTP, dATP or dTTP binding at AS2. Cyclin A2 binding at the C-terminus of SAMHD1 induces disassembly of the SAMHD1 tetramer, |
749906 |
| 3.1.5.B1 | physiological function |
treatment of lung or skin fibroblasts with enzyme-specific siRNA results in the disappearence of enzyme protein accompanied by loss of the cell-cycle regulation of dNTP pool sizes and dNTP imbalance. Cells accumulate in G1 phase with oversized pools and stopp growing. Following removal of the siRNA, the pools are normalized and cell growth restarted, but only after enzyme SAMHD1 has reappeared. In quiescent cultures SAMHD1 down-regulation leads to a marked expansion of dNTP pools. In all cases the largest effect was on dGTP, the preferred substrate of SAMHD1 |
730819 |
