Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

Deoxynucleoside triphosphate triphosphohydrolase 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 forks19525956,21613998,21720370,22056990,23601106,23602554,24336198,26294762,26431200,28229507,28834754,29670289. 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 cells19525956,21613998,21720370,22056990,23364794,23601106,23602554,24336198,25038827,26101257,26294762,26431200,28229507. Likewise, suppresses LINE-1 retrotransposon activity24035396,24217394,29610582. Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx21613998,21720370. In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools23858451. 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 forks23601106,23602554,29610582,29670289. 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 replication29670289. Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation27477283,29670289. Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity29670289. Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity)

Quoted from UniProt’s FUNCTION annotation for Q9Y3Z3 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Nucleoplasm
• Plasma membraneadditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Nucleus · Chromosome

Expression by cell type

Single cell type RNA, the 9 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Schwann cells907.4 nCPM
• Monocyte progenitors510.5 nCPM
• monocytes470 nCPM
• Kupffer cells447.9 nCPM
• cDC445.9 nCPM
• pDCs347.8 nCPM
• Fallopian tube ciliated cells331.7 nCPM
• Macrophages329.5 nCPM
• Endometrial ciliated cells255.1 nCPM