SAMHD1 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. 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. Likewise, suppresses LINE-1 retrotransposon activity. Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx. In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools. 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. 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. 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. Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity. Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation. Belongs to the SAMHD1 family. Expressed in heart, skeletal muscle, spleen, liver, small intestine, placenta, lung and peripheral blood leukocytes (PubMed:11064105). No expression is seen in brain and thymus (PubMed:11064105). 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 3.1.4.-
Chromosomal Location of human Ortholog: 20q11.23
Cellular Component:  nucleoplasm; nucleus; plasma membrane; site of double-strand break; tetraspanin-enriched microdomain
Molecular Function:  deoxynucleoside triphosphate hydrolase activity; dGTP binding; dGTPase activity; GTP binding; identical protein binding; nucleic acid binding; protein binding; RNA binding; RNA nuclease activity; single-stranded DNA binding; triphosphoric monoester hydrolase activity; zinc ion binding
Biological Process:  dATP catabolic process; defense response to virus; deoxyribonucleotide catabolic process; dGTP catabolic process; DNA damage response; DNA strand resection involved in replication fork processing; double-strand break repair via homologous recombination; immune response; innate immune response; negative regulation of type I interferon-mediated signaling pathway; protein homotetramerization; regulation of innate immune response; somatic hypermutation of immunoglobulin genes
Disease: Aicardi-goutieres Syndrome 5; Chilblain Lupus 2
Reference #:  Q9Y3Z3 (UniProtKB)
Alt. Names/Synonyms: CHBL2; DCIP; Dendritic cell-derived IFNG-induced protein; Deoxynucleoside triphosphate triphosphohydrolase SAMHD1; dNTPase; HDDC1; hSAMHD1; Monocyte protein 5; MOP-5; MOP5; SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1; SAM domain and HD domain 1; SAM domain and HD domain-containing protein 1; SAMH1; SAMHD1; SBBI88
Gene Symbols: SAMHD1
Molecular weight: 72,201 Da
Basal Isoelectric point: 6.69  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein