SAMHD1 — SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1

SAMHD1 belongs to a gene co-expression module in 10 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.

SAMHD1's module in each cell type

Cell type	Module	Shares the module with
CD4⁺ T cells	Interferon Response Anti-viral	APOL6, ARL6IP5, BAX, GBP4, GBP5, IFI16, IQGAP1, IRF9 +4 more	View in SCUBA
Endothelial	IFN-gamma Response Inflammation	APOL2, APOL6, BATF2, CARD16, CASP1, CD40, CXCL10, CXCL11 +18 more	View in SCUBA
Fibroblasts	Interferon Response Inflammatory	A4GALT, ABCA1, ABHD17C, BASP1, CCL7, CLEC2B, IFI16, IFI6 +5 more	View in SCUBA
Gamma-delta T cells	Interferon Stimulated Genes Inflammation	AATF, ACSL5, ACTR10, AGL, DDX60, DTX3L, HCLS1, HIF1AN +14 more
Glial cells	Peripheral Nerve Myelination Myelination	ABCA8, AKAP12, CIT, COL27A1, ITGB4, LGI4, NRP2, SYT10	View in SCUBA
Hematopoietic progenitor cells	Myeloid Innate Immune Myeloid development	CCR2, CUX2, CYBB, FXYD7, KCNC3, KIF17, NFKB1, PLD4 +5 more
Macrophages	Endosomal Membrane Trafficking Vesicular traficking	A2M, AP1B1, ARHGAP4, ARHGEF6, ATG4C, B3GNT7, CRTAP, ETV5 +20 more	View in SCUBA
Monocytes	Macrophage Innate Activation Innate immunity	DMXL2, FGL2, HSD17B4, KCTD12, MPEG1, PTPRC, TLR4, VPS35 +1 more	View in SCUBA
Mucosal-associated invariant T cell	T cell Survival Regulation Immune regulation	ACTR3, C11orf98, CISH, FARSA, GIMAP1, GIMAP4, GIMAP5, GIMAP7 +7 more
Natural Killer cells	NK Homing & Residency Homing & TEM	C11orf21, CD47, CTSW, FXYD5, PRMT2, RIPOR2, S1PR4, TFDP2 +2 more	View in SCUBA

About the gene

Synonyms	AGS5, HDDC1, Mg11, MOP-5, SBBI88
Chromosome	20: 36890229-36951893
Predicted location	Intracellular
Essential gene	No
Protein class	Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins
Molecular function	Allosteric enzyme, Hydrolase
Biological process	Antiviral defense, DNA damage, DNA repair, DNA replication, Host-virus interaction, Immunity, Innate immunity

Function

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 (By similarity).

Human Protein Atlas · Open Targets · UniProt

Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.