Affinage

SAMHD1

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 · UniProt Q9Y3Z3

Length
626 aa
Mass
72.2 kDa
Annotated
2026-06-10
100 papers in source corpus 49 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SAMHD1 is an allosterically regulated dNTP triphosphohydrolase that controls intracellular dNTP pools to enforce antiviral restriction and safeguard genome integrity (PMID:21613998, PMID:32576829, PMID:39824836). As the dendritic- and myeloid-cell HIV-1 restriction factor, it blocks reverse transcription in non-dividing cells and is counteracted by lentiviral Vpx, which recruits it to a CRL4 E3 ligase for nuclear proteasomal degradation (PMID:21613998, PMID:22973040). Catalysis proceeds through a bi-metallic iron-magnesium active center that positions a hydroxide nucleophile in-line with the Pα–O5' bond, and full hydrolytic activity requires assembly of an allosterically loaded active homotetramer rather than tetramerization alone (PMID:32576829, PMID:33988981, PMID:39824836). Enzymatic output is tuned by a dense layer of post-translational control: CyclinA2-CDK1/2 phosphorylation at Thr592 destabilizes the tetramer and down-modulates dNTPase activity during S phase, an effect structurally explained by electrostatic disruption of the active tetramer and accelerated subunit dissociation (PMID:25847232, PMID:26294762, PMID:35801923); a reversible cysteine disulfide switch, ARD1-mediated K405 acetylation, and OGT-mediated S93 O-GlcNAcylation further modulate activity and stability, while TRIM21-, USP7-, and NONO/DCAF1-linked ubiquitination pathways set protein levels (PMID:28398823, PMID:28978134, PMID:33391506, PMID:31797533, PMID:37081042, PMID:35803902). Beyond nucleotide pool control, SAMHD1 acts directly in genome maintenance, stimulating MRE11 exonuclease activity at stalled forks to enable restart and recruiting CtIP—governed by SIRT1-mediated K354 deacetylation—to drive DNA end resection and homologous recombination, thereby restraining cytosolic nucleic acid release (PMID:29670289, PMID:28834754, PMID:36344525). It independently suppresses innate immune signaling by binding IKKα/β and disrupting TAK1 engagement to inhibit NF-κB, by interacting with MAVS/IKKε/IRF7 to limit type I IFN induction, and by functioning as an ssRNA 3' exonuclease that prevents immunogenic dsRNA release from condensates (PMID:37100289, PMID:37328105, PMID:36150385). Loss of SAMHD1 elevates dNTP pools and triggers chronic cGAS/STING- and MDA5/MAVS-dependent type I interferon responses, a pathophysiology underlying Aicardi-Goutières syndrome (PMID:24445253, PMID:29670289, PMID:36346347).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2011 High

    Established SAMHD1 as the long-sought myeloid/dendritic-cell HIV-1 restriction factor and the target of lentiviral Vpx, defining its antiviral role.

    Evidence siRNA silencing, overexpression, and Vpx-mediated degradation with viral DNA quantification in non-permissive cells

    PMID:21613998

    Open questions at the time
    • Molecular basis of restriction (dNTPase vs other activities) not yet defined
    • Did not establish where in the cell restriction occurs
  2. 2012 High

    Showed Vpx degrades SAMHD1 through a CRL4 E3 ligase acting on nuclear SAMHD1, localizing the counteraction mechanism and identifying its NLS.

    Evidence NLS mutagenesis, leptomycin B export inhibition, fractionation, and co-IP

    PMID:22973040

    Open questions at the time
    • Did not address why nuclear localization is required for Vpx targeting
    • Antiviral mechanism still unresolved
  3. 2013 High

    Linked SAMHD1 to dNTP pool depletion as the basis of retroviral restriction and revealed that its loss drives spontaneous type I IFN production in vivo.

    Evidence Gene-targeted knockout mice with dNTP measurement, retroviral infection, and IFN gene expression; parallel nucleic-acid-binding biophysics in human cells

    PMID:23371319 PMID:23972988

    Open questions at the time
    • Sensor linking dNTP/SAMHD1 loss to IFN not identified
    • Relative contribution of nucleic-acid binding vs dNTPase unresolved
  4. 2014 High

    Connected dNTP pool dysregulation in SAMHD1-deficient patient cells to genome instability and identified cyclin A/CDK1 cell-cycle phosphorylation, tying enzymatic regulation to the cell cycle; a contested report proposed an RNase activity as the restriction determinant.

    Evidence AGS patient fibroblasts with dNTP/DNA-damage assays and cyclin A co-IP; in vitro RNase assay with D137N/Q548A mutants

    PMID:24445253 PMID:25038827

    Open questions at the time
    • RNase claim disputed by later mouse work (PMID 26667483)
    • Mechanism converting dNTP excess to DNA damage not defined
  5. 2015 High

    Defined the CyclinA2-CDK1/2 phosphorylation site (T592) and showed structurally and kinetically that phosphorylation destabilizes the active tetramer to fine-tune dNTP levels.

    Evidence Cell-cycle synchronization with binding-site mutagenesis and dNTP/checkpoint readouts; crystal structures of T592E/T592V with dNTPase assays; mouse T603 phosphomutant analysis

    PMID:25847232 PMID:26294762 PMID:26667483

    Open questions at the time
    • Phosphatase reversing T592 not identified here
    • Whether RNase contributes to restriction left contradicted
  6. 2016 High

    Placed the cGAS/STING DNA-sensing pathway downstream of SAMHD1 loss and established cell-autonomous restriction requiring reverse transcription, unifying antiviral and inflammatory phenotypes.

    Evidence Genetic epistasis (cGAS/STING KO with SAMHD1 deficiency) in cells and mice; cancer-mutation dNTPase and mutation-rate analyses; 3'-UTR/miRNA regulation in monocytes

    PMID:27071091 PMID:27477283 PMID:27909056

    Open questions at the time
    • Source of the immunostimulatory DNA species not yet defined
    • Tissue-specificity of miRNA regulation incompletely mapped
  7. 2017 High

    Revealed dNTPase-independent genome-protective functions: SAMHD1 recruits CtIP to promote DNA end resection and HR, and is regulated by a redox disulfide switch and K405 acetylation.

    Evidence CRISPR KO with HR reporter, reciprocal SAMHD1–CtIP co-IP, cancer-mutant epistasis; disulfide mapping and dNTPase assays; in vitro acetylation by ARD1

    PMID:28398823 PMID:28834754 PMID:28978134

    Open questions at the time
    • How SAMHD1 is recruited to DSBs not yet defined
    • Physiological trigger of redox switch in vivo unclear
  8. 2018 High

    Showed IFN restricts HIV-1 chiefly by dephosphorylating/activating SAMHD1 via CDK1 downregulation, and demonstrated dNTP-control roles in antibody diversification and stalled-fork repair.

    Evidence CDK1 inhibition/knockdown with phospho-SAMHD1 and HIV infection in macrophages; CRISPR KO in germinal-center B cells with mutation spectra; DNA fiber and MRE11 exonuclease assays with cGAS/STING readouts

    PMID:29669924 PMID:29670289 PMID:29764952

    Open questions at the time
    • Phosphatase mediating IFN-induced dephosphorylation not identified
    • Mechanism of MRE11 stimulation by SAMHD1 biochemically undefined
  9. 2019 High

    Demonstrated that diverse herpesviruses inactivate SAMHD1 by viral-kinase phosphorylation of T592, identified TRIM21-mediated degradation and PIM-kinase-enhanced Vpx counteraction, and uncovered NF-κB suppression as a dNTP-independent antiviral mechanism.

    Evidence In vitro/in vivo viral kinase assays (BGLF4, pUL97, M97) with dNTPase readouts and KO mice; TRIM21 co-IP/ubiquitination; PIM1/3 phospho-Vpx proteomics; ChIP of RELA at the HCMV MIE promoter

    PMID:30739781 PMID:31015445 PMID:31291579 PMID:31291580 PMID:31548682 PMID:31548683 PMID:31797533

    Open questions at the time
    • Mechanistic basis of NF-κB inhibition not yet resolved at this stage
    • Relative in vivo weight of each regulatory PTM unclear
  10. 2020 High

    Refined the catalytic mechanism (bi-metallic Fe-Mg in-line hydrolysis), defined dNTP-control roles in class switch recombination, and identified an IFN-independent TLR4 pathway activating SAMHD1.

    Evidence X-ray crystallography with enzymology; ChIP/CSR assays with dNTP manipulation; TLR4-agonist pathway dissection (TRIF-dependent, CDK1 depletion)

    PMID:32209460 PMID:32511795 PMID:32576829 PMID:32986788

    Open questions at the time
    • How dNTP levels mechanistically shape repair-junction fidelity not fully resolved
    • TLR4-to-SAMHD1 signaling intermediates incompletely mapped
  11. 2021 Medium

    Expanded the PTM and interactome landscape (O-GlcNAcylation, SUMOylation, NONO stabilization) and uncovered dNTP-control roles at transcription-replication conflicts and end-joining junctions.

    Evidence MS site mapping with mutagenesis and antiviral assays (S93 O-GlcNAc, K469/K595/K622 SUMO); NONO co-IP/ubiquitination; R-loop ChIP with RNase H rescue; end-joining substrate assays

    PMID:33391506 PMID:33591315 PMID:33857133 PMID:33988981 PMID:34238351 PMID:35803902

    Open questions at the time
    • Combinatorial interplay among PTMs not addressed
    • Most modification studies are single-lab observations
  12. 2022 High

    Defined SAMHD1 as an ssRNA 3' exonuclease preventing dsRNA-driven IFN, mapped SIRT1-K354 deacetylation as the switch coupling SAMHD1 to CtIP-dependent resection, and ordered cGAS/STING upstream of MDA5/MAVS in SAMHD1-deficient inflammation.

    Evidence In vitro exonuclease assays with condensate imaging and RLR epistasis; SIRT1–SAMHD1 co-IP with K354 mutagenesis and HR assays; double-KO epistasis in mice; cryo-EM with tetramer dissociation kinetics

    PMID:35801923 PMID:36150385 PMID:36344525 PMID:36346347

    Open questions at the time
    • How exonuclease and dNTPase roles are partitioned in vivo unresolved
    • Switch between sensing pathways across cell types unclear
  13. 2023 High

    Mechanistically defined SAMHD1's direct innate-immune suppression (IKKα/β binding disrupting TAK1; MAVS/IKKε/IRF7 axis), and revealed USP7-mediated stabilization and a cytoskeletal/migration role via cortactin in cancer.

    Evidence In vitro binding with purified proteins, reciprocal co-IP and KO/reconstitution for IKK and MAVS/IRF7; USP7 co-IP with K421 mapping and chemosensitivity; cortactin co-IP with FAK/Rac1 and migration assays

    PMID:37009792 PMID:37081042 PMID:37100289 PMID:37328105

    Open questions at the time
    • Integration of NF-κB and IFN suppression with dNTPase activity unclear
    • Migration role is a single-lab observation
  14. 2024 Medium

    Identified a dNTPase-independent cooperation with MX2 in which SAMHD1 binds incoming HIV-1 cores and delivers them to an MX2 trap to block nuclear entry.

    Evidence Co-IP/MS, MX2 KO, SAMHD1 domain mapping, and HIV-1 nuclear import/capsid mutant assays

    PMID:38888311

    Open questions at the time
    • Single-lab finding awaiting independent confirmation
    • Structural basis of core recognition undefined
  15. 2025 High

    Established that allosteric loading of an inactive tetrameric intermediate, not tetramerization per se, governs catalytic efficiency and enables facilitated dNTP depletion.

    Evidence In vitro dNTPase assays with allosteric occupancy analysis, tetramerization assays, and kinetic modeling

    PMID:39824836

    Open questions at the time
    • How cellular ligand fluctuations engage this equilibrium in vivo untested
    • Single-lab reconstitution

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SAMHD1's multiple activities (dNTPase, ssRNA exonuclease, MRE11/CtIP regulation, direct innate-immune-kinase inhibition) are spatially and temporally coordinated, and which dominates in a given cell state, remains unresolved.
  • No unified model integrating enzymatic and non-enzymatic functions
  • Phosphatase reversing T592 not identified in the corpus
  • Mechanism of recruitment to DSBs incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 7 GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 3 GO:0003723 RNA binding 3 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 3 GO:0005829 cytosol 3
Pathway
R-HSA-168256 Immune System 6 R-HSA-73894 DNA Repair 5 R-HSA-1430728 Metabolism 4 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3
Partners
CHUKCTIPIKBKBIRF7MAVSMRE11TRIM21USP7

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx; Vpx induces proteasomal degradation of SAMHD1, and silencing SAMHD1 in non-permissive cell lines alleviates HIV-1 restriction with accumulation of viral DNA, while overexpression in sensitive cells inhibits HIV-1 infection. The putative phosphohydrolase activity is required for restriction. siRNA silencing, overexpression, Vpx-mediated degradation, viral DNA quantification Nature High 21613998
2012 Vpx recruits SAMHD1 to a cullin4A-RING E3 ubiquitin ligase (CRL4) for proteasomal degradation; SAMHD1 contains a conserved nuclear localization sequence (KRPR, residues 11–14) and is targeted by Vpx specifically in the nucleus—cytoplasmic SAMHD1 (NLS-defective) retains antiviral activity but is resistant to Vpx-induced degradation. Nuclear localization sequence mutagenesis, leptomycin B nuclear export inhibition, subcellular fractionation, co-immunoprecipitation Journal of virology High 22973040
2013 SAMHD1 specifically interacts with ssRNA and ssDNA; nucleic acid binding and SAMHD1 complex formation are mutually dependent; interaction requires the HD domain and C-terminal region but not the SAM domain; AGS-associated mutations impair both nucleic acid binding and complex formation. Fluorescence cross-correlation spectroscopy, domain deletion/mutation analysis, co-immunoprecipitation Journal of molecular medicine Medium 23371319
2013 Mouse SAMHD1 reduces cellular dNTP concentrations and restricts retroviral replication in lymphocytes, macrophages, and dendritic cells; absence of SAMHD1 triggers IFN-β-dependent transcriptional upregulation of type I IFN-inducible genes, indicating spontaneous IFN production. Gene-targeted knockout mice, dNTP measurement, retroviral infection assays, interferon gene expression Cell reports High 23972988
2014 SAMHD1 possesses RNase activity; the RNase but not the dNTPase function is essential for HIV-1 restriction. RNase-positive/dNTPase-negative mutant D137N restricts HIV-1; RNase-negative/dNTPase-positive mutant Q548A does not. SAMHD1 associates with and degrades HIV-1 RNA during early infection. Phosphorylation at T592 negatively regulates RNase activity. In vitro RNase assay, point mutagenesis, HIV-1 RNA co-immunoprecipitation, RNA stability assays in macrophages and CD4+ T cells, phosphomimetic mutations Nature medicine Medium 25038827
2014 SAMHD1 deficiency in AGS patient fibroblasts increases dNTP pools, causing genome instability, constitutive DNA damage signaling, cell cycle delay, cellular senescence, and upregulation of IFN-stimulated genes. SAMHD1 is phosphorylated by cyclin A/CDK1 in a cell cycle-dependent manner, with lowest SAMHD1 levels at G1/S phase. Primary patient fibroblasts, dNTP measurement, cell cycle analysis, DNA damage assays, co-immunoprecipitation with cyclin A, fluorescence cross-correlation spectroscopy, synchronized HeLa cells, siRNA knockdown Annals of the rheumatic diseases High 24445253
2015 CyclinA2-CDK1/2 phosphorylates SAMHD1 at Thr-592 via a bipartite cyclinA2-CDK binding site in the SAMHD1 C-terminus; phosphorylation at T592 down-modulates (but does not abolish) SAMHD1 dNTPase activity in S phase to fine-tune dNTP levels during DNA replication; phosphorylation-defective mutants cause DNA damage checkpoint activation and excessive dNTP depletion. Cell cycle synchronization, cyclinA2-CDK binding site mutagenesis, dNTP measurement, DNA damage checkpoint assays, phosphomimetic/phosphodead mutations The Journal of biological chemistry High 25847232
2015 The phosphomimetic T592E mutation reduces SAMHD1 tetramer stability and dNTPase activity; crystal structures of T592E and T592V variants show that the charged T592E induces large conformational changes via electrostatic repulsion, decreasing active tetramer population. Crystal structure determination, in vitro dNTPase assays, tetramer stability assays, phosphomimetic mutations The Journal of biological chemistry High 26294762
2015 SAMHD1 inhibits LINE-1 retrotransposition by promoting cellular stress granule assembly (associated with increased eIF2α phosphorylation and diminished eIF4A/eIF4G interaction), which sequesters LINE-1 RNP in stress granules; depletion of G3BP1 or TIA1 abrogates stress granule formation and overcomes SAMHD1 inhibition. Stress granule marker depletion (siRNA), LINE-1 retrotransposition reporter assay, eIF2α phosphorylation assay, co-immunoprecipitation PLoS genetics Medium 26134849
2015 Murine SAMHD1 antiviral activity is regulated through phosphorylation at threonine 603 (equivalent to human T592) and is limited to non-dividing cells; murine SAMHD1 blocks retroviral infection at the level of reverse transcription; the proposed RNase activity of mouse SAMHD1 had no detectable effect on incoming viral RNA levels. SAMHD1 knockout mouse primary myeloid cells, dNTP measurement, retroviral infection with phosphomutant analysis, viral RNA quantification Retrovirology Medium 26667483
2016 SAMHD1 restricts HIV-1 cell-to-cell transmission from infected T lymphocytes to monocyte-derived dendritic cells and prevents type I interferon response and MxA expression in these coculture settings; Vpx-mediated degradation or siRNA silencing of SAMHD1 increases productive cell-to-cell transmission. Coculture assay with HIV-infected T lymphocytes and MDDCs, siRNA knockdown, Vpx treatment, interferon/MxA measurements Journal of virology Medium 23269793
2016 The spontaneous type I IFN response in SAMHD1-deficient cells and mice requires the cGAS/STING cytosolic DNA-sensing pathway; cell-autonomous lentivirus restriction by SAMHD1 in myeloid cells requires reverse transcription and cGAS/STING signaling, and limits virus-induced IFN production and co-stimulatory marker induction. Genetic epistasis (cGAS/STING KO combined with SAMHD1 deficiency), reverse transcription inhibitor treatment, in vivo mouse infection Cell reports High 27477283
2016 Heterozygous cancer-associated SAMHD1 mutations negatively affect dNTPase activity; inactivation of one SAMHD1 allele is sufficient to elevate dNTP pools in mouse embryos; minor dNTP pool changes combined with inactivated mismatch repair dramatically increase mutation rates. Enzymatic activity assays of mutant proteins, dNTP measurement in mouse embryos, mutation rate analysis in yeast/cell models Proceedings of the National Academy of Sciences High 27071091
2017 SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by homologous recombination; SAMHD1 is recruited to DSBs; SAMHD1 complexes with CtIP via a conserved C-terminal domain and recruits CtIP to DSBs; a cancer-associated mutant with impaired CtIP interaction (but not a dNTPase-inactive mutant) fails to rescue the end resection impairment. CRISPR/Cas9 knockout, Vpx-mediated degradation, co-immunoprecipitation (SAMHD1–CtIP complex), recruitment to DSBs by ChIP/imaging, HR reporter assay, domain deletion mutagenesis Cell reports High 28834754
2017 SAMHD1 dNTPase activity is regulated by a redox switch: three cysteine residues form an intrachain disulfide bond that reversibly inhibits protein tetramerization and catalysis; proliferative signals lead to SAMHD1 oxidation in cells, and oxidized SAMHD1 localizes outside the nucleus. Biochemical identification of disulfide bonds, dNTPase activity assays, cell fractionation, redox manipulation Antioxidants & redox signaling Medium 28398823
2017 SAMHD1 acetylation at lysine 405 by ARD1 acetyltransferase enhances dNTPase activity in vitro; non-acetylated K405R mutant-expressing cancer cells have reduced G1/S transition and slower proliferation; acetylation levels are strongest during G1 phase. In vitro acetylation assay, dNTPase activity measurement, K405R mutagenesis, cell cycle analysis, co-immunoprecipitation Oncotarget Medium 28978134
2018 SAMHD1 promotes degradation of nascent DNA at stalled replication forks by stimulating the exonuclease activity of MRE11, which activates the ATR-CHK1 checkpoint and allows fork restart; in SAMHD1-depleted cells, ssDNA fragments accumulate in the cytosol and activate the cGAS-STING pathway to induce type I interferons. DNA fiber assay (fork restart), MRE11 exonuclease assay, siRNA knockdown, cGAS/STING pathway activation measurement, cytosolic ssDNA detection Nature High 29670289
2018 SAMHD1 dephosphorylation at T592 (activating the protein) is the predominant mechanism of HIV-1 restriction induced by type I, II, and III IFN signaling in macrophages; all IFN types downregulated CDK1 protein expression; pharmacological CDK1 inhibition or siRNA knockdown phenocopied IFN effects on SAMHD1; viral restriction imposed by IFNs or dasatinib was overcome by SAMHD1 depletion. SAMHD1 phosphorylation state analysis, CDK1 knockdown/inhibition, IFN treatment, HIV-1 infection assay in primary macrophages, SAMHD1 knockdown rescue experiments mBio High 29764952
2018 SAMHD1 promotes immunoglobulin hypermutation by restricting dNTP supply; CRISPR inactivation of SAMHD1 in germinal center B cells increased transition mutations at C:G base pairs and substantially decreased transversion mutations at A:T and C:G base pairs, indicating that dNTP starvation by SAMHD1 enhances AID mutagenicity. CRISPR/Cas9 knockout in germinal center B cells, Ig hypermutation sequencing, dNTP measurement Proceedings of the National Academy of Sciences Medium 29669924
2019 EBV protein kinase BGLF4 phosphorylates SAMHD1 and inhibits its dNTPase activity; this mechanism of phosphorylation-based SAMHD1 inactivation is shared by beta- and gamma-herpesviruses (conserved viral protein kinases). In vitro kinase assay, dNTPase activity measurement, viral infection assays, phosphorylation site mapping Cell reports Medium 31291580
2019 SAMHD1 modulates early steps of HCMV infection by suppressing NF-κB activation; SAMHD1 depletion increases HCMV gene expression from the major immediate-early promoter independently of dNTP levels; SAMHD1 inhibits NF-κB, and increased RELA and RNA polymerase II occupy the HCMV MIE promoter in SAMHD1-depleted cells; HCMV viral kinase UL97 phosphorylates SAMHD1 during infection. SAMHD1 depletion, ChIP (RELA, RNA Pol II), NF-κB reporter assay, viral gene expression measurement, phosphorylation assays Cell reports High 31291579
2019 HCMV overcomes SAMHD1 restriction in macrophages by using the viral kinase pUL97 (and by hijacking cellular kinases) to phosphorylate SAMHD1 at T592, converting it to its inactive form; HCMV also interferes with SAMHD1 steady-state expression. SAMHD1 phosphorylation assays in infected cells, viral kinase pUL97 functional analysis, dNTP measurement Nature microbiology Medium 31548682
2019 Murine CMV viral kinase M97 counteracts SAMHD1 restriction in vivo by phosphorylating the regulatory residue T603; phosphorylation correlated with reduced dNTP hydrolase activity and loss of viral restriction; SAMHD1 inhibits MCMV replication in vivo in a SAMHD1 knockout mouse model. SAMHD1 knockout mice, MCMV infection in vivo and in vitro, viral kinase M97 phosphorylation assay, dNTPase activity measurement Nature microbiology High 31548683
2019 TRIM21 E3 ubiquitin ligase specifically interacts with SAMHD1 and promotes its proteasomal degradation; ubiquitination occurs at K622 on SAMHD1; phosphorylation of SAMHD1 at T592 also blocks EV71 restriction; TRIM21-mediated SAMHD1 degradation affects HIV-1 restriction and interferon regulation. Co-immunoprecipitation, ubiquitination assay, proteasome inhibition, domain mutagenesis, EV71 and HIV-1 infection assays EMBO reports Medium 31797533
2019 PIM1 and PIM3 serine/threonine kinases phosphorylate HIV-2 Vpx at Ser13, stabilizing the Vpx–SAMHD1 interaction and promoting ubiquitin-mediated proteolysis of SAMHD1; PIM kinase inhibition promotes SAMHD1 antiviral activity and reduces viral replication. Integrated proteomics, in vitro kinase assay, co-immunoprecipitation, ubiquitination assay, viral replication assay with PIM inhibitors/knockdown Nature communications Medium 31015445
2019 SAMHD1 is a nucleocytoplasmic shuttling protein; altering subcellular localization by mutating/removing NLS enhances SAMHD1's potency in LINE-1 suppression; cytoplasmic SAMHD1 leads to enhanced depletion of LINE-1 ORF2p. Digitonin-based cytoplasm/nucleus fractionation, NLS mutagenesis, exportin Xpo1 overexpression, LINE-1 retrotransposition reporter assay Biochemical and biophysical research communications Medium 30739781
2019 SAMHD1 competitively interacts with VP1 of EV71 and EVD68 at the same domain that binds VP2, thereby interfering with VP1–VP2 interaction and viral capsid assembly; this mechanism is independent of dNTPase or RNase activity; T592A mutant maintains this inhibitory effect but T592D mutant does not. Co-immunoprecipitation, competitive binding assay, viral assembly assay, phosphomutant analysis Journal of virology Medium 33883225
2020 Crystal structures reveal that SAMHD1 utilizes a bi-metallic iron-magnesium active-site center that positions a hydroxide nucleophile in-line with the Pα–O5' bond to catalyze phosphoester bond hydrolysis of dNTPs. X-ray crystallography of SAMHD1 inhibitor complexes, enzymological assays Nature communications High 32576829
2020 TLR4 activation induces G0 arrest and SAMHD1 antiretroviral activity via an IFN-independent pathway requiring TRIF but not TBK1, IRF3, Myd88, or NF-κB; this involves p21 upregulation and CDK1 depletion, leading to SAMHD1 dephosphorylation at T592; SAMHD1 knockdown confirmed that TLR4-activated HIV-1 block is specifically mediated by SAMHD1. TLR4 agonist treatment, TRIF/TBK1/IRF3/Myd88 inhibition, SAMHD1 phosphorylation assay, CDK1 level measurement, SAMHD1 knockdown, HIV-1 infection assay Cell reports High 32209460
2020 HCMV infection induces rapid SAMHD1 phosphorylation at T592 by cellular Cdk2 and viral kinase pUL97, resulting in a significant fraction of phospho-SAMHD1 relocating to the cytoplasm of infected fibroblasts in association with viral particles and dense bodies. SAMHD1 phosphorylation analysis, subcellular fractionation, co-localization with viral particles by imaging PLoS pathogens Medium 32986788
2020 SAMHD1-mediated dNTP degradation is required for efficient DNA repair during immunoglobulin class switch recombination (CSR); SAMHD1 localizes at the Ig switch region; SAMHD1 depletion impairs CSR and IgH/c-Myc translocation; elevated dNTP pools increase nucleotide insertions at break-point junctions. ChIP (SAMHD1 at Ig switch region), CSR assay, translocation assay, nucleotide pool manipulation, SAMHD1 siRNA depletion The EMBO journal High 32511795
2021 OGT-mediated O-GlcNAcylation of SAMHD1 at Ser93 stabilizes SAMHD1 and enhances its antiviral activity against HBV; HBP/O-GlcNAcylation positively regulates SAMHD1-dependent antiviral response in vitro and in vivo. LC-MS identification of O-GlcNAc site, co-immunoprecipitation, OGT overexpression/knockdown, HBV replication assay, S93 mutagenesis Theranostics Medium 33391506
2021 TRAF6 and TAK1 contribute to SAMHD1-mediated suppression of NF-κB activation; SAMHD1 inhibits TAK1 activation and TRAF6 signaling; TRAF6 knockdown in SAMHD1-deficient cells significantly inhibited HIV-1 infection and NF-κB activation; the NLS is not required for this suppressive function. SAMHD1 CRISPR KO, TRAF6 siRNA knockdown, TAK1 pharmacological inhibition, IκBα phosphorylation assay, TNF-α mRNA measurement, HIV-1 infection assay, NF-κB reporter Journal of virology Medium 33177202
2021 PIAS1 E3 SUMO ligase interacts with SAMHD1 and promotes its SUMOylation at K469, K595, and K622; SUMOylation-deficient SAMHD1 loses anti-EBV activity; SAMHD1 association with EBV genome is PIAS1-dependent. Co-immunoprecipitation, SUMOylation assay, site mutagenesis (K469R/K595R/K622R), ChIP (SAMHD1 on EBV genome), EBV replication assay Cell & bioscience Medium 34238351
2021 SAMHD1 dNTPase activity restrains aberrant nucleotide insertions at DNA break repair junctions during end joining; SAMHD1 expression or low intracellular dNTPs leads to shorter repair joints and impedes insertion of distant DNA regions prior to end repair. Linear DNA substrate end-joining assay in HEK293 cells, CRISPR/Cas9-induced break monitoring, SAMHD1 dNTPase mutant analysis Nucleic acids research Medium 33591315
2021 R-loops are highly enriched at transcription-replication conflict regions in SAMHD1-deficient cells; SAMHD1 loss leads to R-loop accumulation and activation of DNA damage responses; removal of R-loops in SAMHD1 deficiency reduces cellular responses to genome instability. R-loop immunofluorescence/ChIP (S9.6 antibody), DNA damage response markers, R-loop removal by RNase H overexpression, SAMHD1 patient fibroblasts PLoS genetics Medium 33857133
2022 SAMHD1 functions as a single-stranded RNA (ssRNA) 3' exonuclease; loss of SAMHD1 causes cellular RNA accumulation, leading to dissolution of RNA-protein condensates that sequester immunogenic dsRNA; released dsRNA triggers type I IFN activation via RIG-I-like receptors. ssRNA exonuclease assay, RNA sequencing (RNA accumulation), condensate dissolution imaging, RIG-I-like receptor epistasis, SAMHD1 KO cells Molecular cell High 36150385
2022 SIRT1 deacetylase complexes with SAMHD1 and deacetylates it at conserved K354 specifically in response to DSBs; K354 deacetylation promotes SAMHD1 recruitment to DSBs and binding to ssDNA, which facilitates CtIP ssDNA binding and promotes DNA end resection and HR, without affecting tetramerization or dNTPase activity. Co-immunoprecipitation (SIRT1–SAMHD1), K354 mutagenesis, DSB recruitment assay (ChIP/imaging), ssDNA binding assay, HR reporter assay, CtIP ssDNA binding Nature communications High 36344525
2022 In SAMHD1-deficient mice, the chronic IFN response is driven by the MDA5/MAVS pathway but requires functional priming through the cGAS/STING pathway; cGAS/STING is positioned upstream of tonic IFN signaling in Samhd1-deficient mice. Genetic epistasis (Samhd1 KO crossed with cGAS/STING KO and MDA5/MAVS KO), IFN measurement, tumor-free survival analysis The Journal of experimental medicine High 36346347
2022 Phosphorylation at T592 accelerates SAMHD1 tetramer dissociation (~15-fold) and increases C-terminal domain dynamics; ssDNA binds competitively with GTP to the A1 allosteric site; cryo-EM structure reveals substantial dynamics in the C-terminal domain containing T592. Cryo-EM structure, tetramer dissociation kinetics, ssDNA binding assay, GTP competition assay, phosphomimetic mutations Nucleic acids research High 35801923
2023 SAMHD1 suppresses NF-κB activation by directly interacting (via its HD domain) with IKKα and IKKβ; SAMHD1 suppresses phosphorylation of IKKα/β/γ, inhibiting downstream IκBα phosphorylation; SAMHD1 disrupts the interaction between upstream kinase TAK1 and IKKα or IKKβ; direct in vitro binding between recombinant SAMHD1 and purified IKKα or IKKβ was demonstrated. Co-immunoprecipitation (endogenous and recombinant), in vitro binding assay with purified proteins, SAMHD1 KO/reconstitution, domain mapping, IKK phosphorylation assay The Journal of biological chemistry High 37100289
2023 SAMHD1 inhibits type I IFN induction through the MAVS, IKKε, and IRF7 signaling axis; SAMHD1 interacts with MAVS and suppresses MAVS aggregation upon Sendai virus infection; SAMHD1 prevents IRF7 binding to the kinase domain of IKKε; the SAMHD1 interaction with the inhibitory domain of IRF7 (IRF7-ID) is necessary and sufficient for SAMHD1 suppression of IRF7-mediated IFN-I activation. Co-immunoprecipitation (SAMHD1–MAVS, SAMHD1–IRF7), MAVS aggregation assay, IRF7-IKKε binding assay, HEK293T reporter assay, IRF7-ID mutagenesis, computational docking/molecular dynamics The Journal of biological chemistry High 37328105
2023 Deubiquitinase USP7 interacts with SAMHD1 and deubiquitinates it at K421, stabilizing SAMHD1 protein expression; stabilized SAMHD1 interacts with CtIP to promote DNA damage repair; USP7 inhibition sensitizes tumor cells to chemotherapeutic agents by decreasing SAMHD1. Co-immunoprecipitation (USP7–SAMHD1), ubiquitination site mapping (K421), USP7 inhibitor treatment, DNA damage repair assay, chemosensitivity assay Oncogene Medium 37081042
2023 SAMHD1 contributes to cancer cell migration in ccRCC by participating in endocytosis and lamellipodia formation; SAMHD1 binds cortactin to form an endosomal complex, and SAMHD1-stimulated endosomal FAK signaling activates Rac1, promoting lamellipodia formation and cell motility. Co-immunoprecipitation (SAMHD1–cortactin), FAK signaling assays, Rac1 activation assay, lamellipodia imaging, cell migration assay, patient tissue correlation Experimental & molecular medicine Medium 37009792
2024 SAMHD1 cooperates with MX2 to inhibit HIV-1 at the post-cDNA-synthesis stage by recognizing and binding incoming HIV-1 cores and delivering them to the MX2 molecular trap, blocking nuclear entry; SAMHD1 mutants unable to recognize HIV-1 core showed substantially decreased antiviral activity; this mechanism is distinct from dNTP hydrolysis. Immunoprecipitation plus mass spectrometry (SAMHD1–MX2), MX2 KO (endogenous disruption), SAMHD1 domain mapping, HIV-1 nuclear import assay, HIV-1 capsid mutant analysis mBio Medium 38888311
2025 SAMHD1 tetramerization alone is insufficient for dNTP hydrolysis; activation requires an inactive tetrameric intermediate with partially occupied allosteric sites; the equilibrium between inactive and active tetrameric states regulates dNTPase activity driven by binding/dissociation of additional allosteric dNTP ligands; catalytic efficiency (but not substrate specificity) is modulated by the identity of dNTPs at allosteric sites; SAMHD1 exhibits facilitated dNTP depletion, whereby increased biosynthesis of certain dNTPs enhances depletion of others. In vitro dNTPase assays, allosteric site occupancy analysis, tetramerization assays, kinetic modeling Nature communications High 39824836
2021 NONO interacts with SAMHD1 and stabilizes it by inhibiting DCAF1-mediated ubiquitination/degradation; NONO overexpression increases SAMHD1 expression and reduces AML cell sensitivity to Ara-C. Co-immunoprecipitation (NONO–SAMHD1), ubiquitination assay with DCAF1, NONO overexpression/knockdown, cytarabine sensitivity assay Cell death & disease Medium 35803902
2021 Sp-dNTPαS diastereomers (but not Rp-dNTPαS) prevent Mg2+ coordination at allosteric and catalytic sites, rendering SAMHD1 unable to form stable active homotetramers or hydrolyze substrates; Sp-dNTPαS competitively inhibits dNTP hydrolysis; a co-crystal structure of SAMHD1 with Rp-dGTPαS reveals an Fe-Mg-bridging water species poised for nucleophilic attack on Pα. X-ray crystallography (SAMHD1–Rp-dGTPαS cocrystal), in vitro dNTPase kinetics, tetramerization assay, stereospecific substrate analysis Biochemistry High 33988981
2016 Interferon induction of SAMHD1 in primary human monocytes depends on post-transcriptional regulation via 3'-UTR; miR-181a and miR-30a target the SAMHD1 3'-UTR and their down-regulation inversely correlates with SAMHD1 protein up-regulation upon type I and II IFN stimulation in monocytes; this miRNA-dependent regulation does not occur in macrophages or dendritic cells. Luciferase 3'-UTR reporter assay, miRNA overexpression/inhibition, miRNA-SAMHD1 correlation in primary monocytes, AGO2 co-immunoprecipitation The Journal of biological chemistry Medium 27909056

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 1267 21613998
2015 Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. American journal of medical genetics. Part A 507 25604658
2013 Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. The Lancet. Neurology 371 24183309
2018 SAMHD1 acts at stalled replication forks to prevent interferon induction. Nature 366 29670289
2014 The ribonuclease activity of SAMHD1 is required for HIV-1 restriction. Nature medicine 240 25038827
2017 SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination. Cell reports 158 28834754
2013 Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response. Cell reports 141 23972988
2014 SAMHD1 prevents autoimmunity by maintaining genome stability. Annals of the rheumatic diseases 131 24445253
2012 The Vpx lentiviral accessory protein targets SAMHD1 for degradation in the nucleus. Journal of virology 117 22973040
2015 SAMHD1 Inhibits LINE-1 Retrotransposition by Promoting Stress Granule Formation. PLoS genetics 111 26134849
2016 Restriction by SAMHD1 Limits cGAS/STING-Dependent Innate and Adaptive Immune Responses to HIV-1. Cell reports 98 27477283
2016 Heterozygous colon cancer-associated mutations of SAMHD1 have functional significance. Proceedings of the National Academy of Sciences of the United States of America 97 27071091
2011 Homozygous mutation in SAMHD1 gene causes cerebral vasculopathy and early onset stroke. Proceedings of the National Academy of Sciences of the United States of America 95 21402907
2015 CyclinA2-Cyclin-dependent Kinase Regulates SAMHD1 Protein Phosphohydrolase Domain. The Journal of biological chemistry 85 25847232
2016 SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells. Virology 81 27183329
2015 SAMHD1: at the crossroads of cell proliferation, immune responses, and virus restriction. Trends in microbiology 78 26439297
2020 SAMHD1 Functions and Human Diseases. Viruses 74 32244340
2013 Single-stranded nucleic acids promote SAMHD1 complex formation. Journal of molecular medicine (Berlin, Germany) 72 23371319
2015 Impaired dNTPase activity of SAMHD1 by phosphomimetic mutation of Thr-592. The Journal of biological chemistry 71 26294762
2019 Conserved Herpesvirus Protein Kinases Target SAMHD1 to Facilitate Virus Replication. Cell reports 68 31291580
2017 SAMHD1 protects cancer cells from various nucleoside-based antimetabolites. Cell cycle (Georgetown, Tex.) 62 28436707
2016 Restrictive influence of SAMHD1 on Hepatitis B Virus life cycle. Scientific reports 60 27229711
2011 How SAMHD1 changes our view of viral restriction. Trends in immunology 60 22177690
2014 SAMHD1 is down regulated in lung cancer by methylation and inhibits tumor cell proliferation. Biochemical and biophysical research communications 58 25449277
2019 TRIM21-mediated proteasomal degradation of SAMHD1 regulates its antiviral activity. EMBO reports 56 31797533
2017 SAMHD1 acetylation enhances its deoxynucleotide triphosphohydrolase activity and promotes cancer cell proliferation. Oncotarget 54 28978134
2021 Hexosamine biosynthetic pathway promotes the antiviral activity of SAMHD1 by enhancing O-GlcNAc transferase-mediated protein O-GlcNAcylation. Theranostics 53 33391506
2019 SAMHD1 Modulates Early Steps during Human Cytomegalovirus Infection by Limiting NF-κB Activation. Cell reports 53 31291579
2012 SAMHD1 restricts HIV-1 cell-to-cell transmission and limits immune detection in monocyte-derived dendritic cells. Journal of virology 53 23269793
2018 SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia. Blood cancer journal 49 29352181
2018 SAMHD1 and the innate immune response to cytosolic DNA during DNA replication. Current opinion in immunology 48 30292848
2013 SAMHD1 host restriction factor: a link with innate immune sensing of retrovirus infection. Journal of molecular biology 47 24161438
2018 SAMHD1 Suppression of Antiviral Immune Responses. Trends in microbiology 46 30336972
2017 DNA damage induced by topoisomerase inhibitors activates SAMHD1 and blocks HIV-1 infection of macrophages. The EMBO journal 46 29084722
2016 Interferons Induce Expression of SAMHD1 in Monocytes through Down-regulation of miR-181a and miR-30a. The Journal of biological chemistry 45 27909056
2021 Aicardi-Goutières syndrome-associated gene SAMHD1 preserves genome integrity by preventing R-loop formation at transcription-replication conflict regions. PLoS genetics 43 33857133
2019 Human cytomegalovirus overcomes SAMHD1 restriction in macrophages via pUL97. Nature microbiology 43 31548682
2017 The SAMHD1 dNTP Triphosphohydrolase Is Controlled by a Redox Switch. Antioxidants & redox signaling 43 28398823
2022 SAMHD1 controls innate immunity by regulating condensation of immunogenic self RNA. Molecular cell 42 36150385
2015 Phosphorylation of murine SAMHD1 regulates its antiretroviral activity. Retrovirology 42 26667483
2011 SAMHD1: a new insight into HIV-1 restriction in myeloid cells. Retrovirology 42 21740548
2015 Low SAMHD1 expression following T-cell activation and proliferation renders CD4+ T cells susceptible to HIV-1. AIDS (London, England) 40 25715102
2020 Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis. Nature communications 39 32576829
2018 SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate immunity. Autoimmunity 39 29583030
2017 With me or against me: Tumor suppressor and drug resistance activities of SAMHD1. Experimental hematology 38 28502830
2018 SAMHD1 Phosphorylation Coordinates the Anti-HIV-1 Response by Diverse Interferons and Tyrosine Kinase Inhibition. mBio 37 29764952
2019 SAMHD1 Regulates Human Papillomavirus 16-Induced Cell Proliferation and Viral Replication during Differentiation of Keratinocytes. mSphere 36 31391281
2015 A High-Throughput Enzyme-Coupled Assay for SAMHD1 dNTPase. Journal of biomolecular screening 36 25755265
2022 Deficiency for SAMHD1 activates MDA5 in a cGAS/STING-dependent manner. The Journal of experimental medicine 35 36346347
2023 Activation of STING by SAMHD1 Deficiency Promotes PANoptosis and Enhances Efficacy of PD-L1 Blockade in Diffuse Large B-cell Lymphoma. International journal of biological sciences 32 37781035
2021 SAMHD1 in cancer: curse or cure? Journal of molecular medicine (Berlin, Germany) 31 34480199
2020 TLR4-Mediated Pathway Triggers Interferon-Independent G0 Arrest and Antiviral SAMHD1 Activity in Macrophages. Cell reports 31 32209460
2017 A SAMHD1 mutation associated with Aicardi-Goutières syndrome uncouples the ability of SAMHD1 to restrict HIV-1 from its ability to downmodulate type I interferon in humans. Human mutation 31 28229507
2014 MicroRNA-181 expression regulates specific post-transcriptional level of SAMHD1 expression in vitro. Biochemical and biophysical research communications 30 25201733
2022 SAMHD1 silencing cooperates with radiotherapy to enhance anti-tumor immunity through IFI16-STING pathway in lung adenocarcinoma. Journal of translational medicine 28 36578072
2021 SAMHD1 … and Viral Ways around It. Viruses 28 33801276
2020 SAMHD1 is a key regulator of the lineage-specific response of acute lymphoblastic leukaemias to nelarabine. Communications biology 28 32581304
2016 Exogenous expression of SAMHD1 inhibits proliferation and induces apoptosis in cutaneous T-cell lymphoma-derived HuT78 cells. Cell cycle (Georgetown, Tex.) 28 27929746
2012 Identification and characterization of naturally occurring splice variants of SAMHD1. Retrovirology 28 23092512
2017 The Dynamic Interplay between HIV-1, SAMHD1, and the Innate Antiviral Response. Frontiers in immunology 27 29176984
2022 SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks. Nature communications 26 36344525
2019 SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts. International journal of molecular sciences 26 30959732
2018 SAMHD1 deficient human monocytes autonomously trigger type I interferon. Molecular immunology 25 30099227
2016 Impact of clinically tested NEP/ACE inhibitors on tumor uptake of [(111)In-DOTA]MG11-first estimates for clinical translation. EJNMMI research 25 26882895
2019 A dual role for SAMHD1 in regulating HBV cccDNA and RT-dependent particle genesis. Life science alliance 24 30918010
2019 Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction. mBio 24 31744918
2017 Roles of SAMHD1 in antiviral defense, autoimmunity and cancer. Reviews in medical virology 24 28444859
2021 TRAF6 and TAK1 Contribute to SAMHD1-Mediated Negative Regulation of NF-κB Signaling. Journal of virology 23 33177202
2019 A viral kinase counteracts in vivo restriction of murine cytomegalovirus by SAMHD1. Nature microbiology 23 31548683
2018 SAMHD1 enhances immunoglobulin hypermutation by promoting transversion mutation. Proceedings of the National Academy of Sciences of the United States of America 23 29669924
2020 SAMHD1-mediated dNTP degradation is required for efficient DNA repair during antibody class switch recombination. The EMBO journal 21 32511795
2014 SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse myeloid cells. PloS one 21 24586870
2023 De-ubiquitination of SAMHD1 by USP7 promotes DNA damage repair to overcome oncogenic stress and affect chemotherapy sensitivity. Oncogene 20 37081042
2020 SAMHD1 phosphorylation and cytoplasmic relocalization after human cytomegalovirus infection limits its antiviral activity. PLoS pathogens 20 32986788
2019 PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation. Nature communications 20 31015445
2021 SAMHD1 restrains aberrant nucleotide insertions at repair junctions generated by DNA end joining. Nucleic acids research 18 33591315
2019 Nucleocytoplasmic shuttling of SAMHD1 is important for LINE-1 suppression. Biochemical and biophysical research communications 18 30739781
2017 SAMHD1 Sheds Moonlight on DNA Double-Strand Break Repair. Trends in genetics : TIG 18 28969870
2021 SAMHD1 Inhibits Multiple Enteroviruses by Interfering with the Interaction between VP1 and VP2 Proteins. Journal of virology 17 33883225
2019 Intertwined: SAMHD1 cellular functions, restriction, and viral evasion strategies. Medical microbiology and immunology 17 30879196
2019 The missing link: allostery and catalysis in the anti-viral protein SAMHD1. Biochemical Society transactions 17 31296733
2021 PIAS1 potentiates the anti-EBV activity of SAMHD1 through SUMOylation. Cell & bioscience 16 34238351
2019 The ability of SAMHD1 to block HIV-1 but not SIV requires expression of MxB. Virology 16 30959264
2019 Positive selection in dNTPase SAMHD1 throughout mammalian evolution. Proceedings of the National Academy of Sciences of the United States of America 16 31451672
2015 Degradation of SAMHD1 by Vpx Is Independent of Uncoating. Journal of virology 16 25762741
2023 The host antiviral protein SAMHD1 suppresses NF-κB activation by interacting with the IKK complex during inflammatory responses and viral infection. The Journal of biological chemistry 15 37100289
2022 Elimination of Aicardi-Goutières syndrome protein SAMHD1 activates cellular innate immunity and suppresses SARS-CoV-2 replication. The Journal of biological chemistry 15 35085552
2022 Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML. Cell death & disease 15 35803902
2022 Interferon-inducible SAMHD1 restricts viral replication through downregulation of lipid synthesis. Frontiers in immunology 15 36532074
2021 Probing the Catalytic Mechanism and Inhibition of SAMHD1 Using the Differential Properties of Rp- and Sp-dNTPαS Diastereomers. Biochemistry 15 33988981
2016 Functional organization of human SAMHD1 and mechanisms of HIV-1 restriction. Biological chemistry 15 26733158
2019 SAMHD1-deficient fibroblasts from Aicardi-Goutières Syndrome patients can escape senescence and accumulate mutations. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 31914608
2022 Phosphorylation of SAMHD1 Thr592 increases C-terminal domain dynamics, tetramer dissociation and ssDNA binding kinetics. Nucleic acids research 13 35801923
2020 Involvement of SAMHD1 in dNTP homeostasis and the maintenance of genomic integrity and oncotherapy (Review). International journal of oncology 13 32319570
2018 DNA damage induces a SAMHD1-mediated block to the infection of macrophages by HIV-1. Scientific reports 13 29515139
2025 SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs. Nature communications 12 39824836
2024 The SAMHD1-MX2 axis restricts HIV-1 infection at postviral DNA synthesis. mBio 12 38888311
2023 SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion. Experimental & molecular medicine 12 37009792
2023 SAMHD1 impairs type I interferon induction through the MAVS, IKKε, and IRF7 signaling axis during viral infection. The Journal of biological chemistry 12 37328105
2020 SAMHD1 as the Potential Link Between SARS-CoV-2 Infection and Neurological Complications. Frontiers in neurology 12 33101175

Missed literature

Know a paper Affinage missed for SAMHD1? Flag it for the maintainers and the community.

No submissions yet.