ID SAMH1_MOUSE Reviewed; 658 AA. AC Q60710; E9Q0K6; F8WJE0; Q3U5X2; Q543A4; Q91VK8; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 18-JUL-2018, sequence version 3. DT 27-MAR-2024, entry version 186. DE RecName: Full=Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 {ECO:0000305}; DE Short=dNTPase {ECO:0000305}; DE EC=3.1.5.- {ECO:0000269|PubMed:29379009, ECO:0000269|PubMed:31548683}; DE AltName: Full=Interferon-gamma-inducible protein Mg11 {ECO:0000303|PubMed:7884320}; DE AltName: Full=SAM domain and HD domain-containing protein 1 {ECO:0000305}; DE Short=mSAMHD1 {ECO:0000303|PubMed:29379009}; GN Name=Samhd1 {ECO:0000312|MGI:MGI:1927468}; GN Synonyms=Mg21 {ECO:0000303|PubMed:7884320}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-658 (ISOFORM 1). RC TISSUE=Macrophage; RX PubMed=7884320; DOI=10.1002/jlb.57.3.477; RA Lafuse W.P., Brown D., Castle L., Zwilling B.S.; RT "Cloning and characterization of a novel cDNA that is IFN-gamma-induced in RT mouse peritoneal macrophages and encodes a putative GTP-binding protein."; RL J. Leukoc. Biol. 57:477-483(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 22-658 (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Ovary; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-658 (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Brain, and Mammary gland; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49; THR-52 AND THR-634, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-634, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of electron RT capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [7] RP INDUCTION. RX PubMed=19525956; DOI=10.1038/ng.373; RA Rice G.I., Bond J., Asipu A., Brunette R.L., Manfield I.W., Carr I.M., RA Fuller J.C., Jackson R.M., Lamb T., Briggs T.A., Ali M., Gornall H., RA Couthard L.R., Aeby A., Attard-Montalto S.P., Bertini E., Bodemer C., RA Brockmann K., Brueton L.A., Corry P.C., Desguerre I., Fazzi E., RA Cazorla A.G., Gener B., Hamel B.C.J., Heiberg A., Hunter M., RA van der Knaap M.S., Kumar R., Lagae L., Landrieu P.G., Lourenco C.M., RA Marom D., McDermott M.F., van der Merwe W., Orcesi S., Prendiville J.S., RA Rasmussen M., Shalev S.A., Soler D.M., Shinawi M., Spiegel R., Tan T.Y., RA Vanderver A., Wakeling E.L., Wassmer E., Whittaker E., Lebon P., RA Stetson D.B., Bonthron D.T., Crow Y.J.; RT "Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as RT regulator of the innate immune response."; RL Nat. Genet. 41:829-832(2009). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49; THR-52; SER-55; THR-56 RP AND THR-634, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [9] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=23972988; DOI=10.1016/j.celrep.2013.07.037; RA Behrendt R., Schumann T., Gerbaulet A., Nguyen L.A., Schubert N., RA Alexopoulou D., Berka U., Lienenklaus S., Peschke K., Gibbert K., RA Wittmann S., Lindemann D., Weiss S., Dahl A., Naumann R., Dittmer U., RA Kim B., Mueller W., Gramberg T., Roers A.; RT "Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous RT cell-intrinsic antiviral response."; RL Cell Rep. 4:689-696(2013). RN [10] RP FUNCTION, DISRUPTION PHENOTYPE, AND ALTERNATIVE SPLICING (ISOFORMS 1 AND RP 2). RX PubMed=23872947; DOI=10.1038/emboj.2013.163; RA Rehwinkel J., Maelfait J., Bridgeman A., Rigby R., Hayward B., RA Liberatore R.A., Bieniasz P.D., Towers G.J., Moita L.F., Crow Y.J., RA Bonthron D.T., Reis e Sousa C.; RT "SAMHD1-dependent retroviral control and escape in mice."; RL EMBO J. 32:2454-2462(2013). RN [11] RP FUNCTION, PHOSPHORYLATION AT THR-634, AND MUTAGENESIS OF THR-634. RX PubMed=26667483; DOI=10.1186/s12977-015-0229-6; RA Wittmann S., Behrendt R., Eissmann K., Volkmann B., Thomas D., Ebert T., RA Cribier A., Benkirane M., Hornung V., Bouzas N.F., Gramberg T.; RT "Phosphorylation of murine SAMHD1 regulates its antiretroviral activity."; RL Retrovirology 12:103-103(2015). RN [12] RP FUNCTION. RX PubMed=29669924; DOI=10.1073/pnas.1719771115; RA Thientosapol E.S., Bosnjak D., Durack T., Stevanovski I., RA van Geldermalsen M., Holst J., Jahan Z., Shepard C., Weninger W., Kim B., RA Brink R., Jolly C.J.; RT "SAMHD1 enhances immunoglobulin hypermutation by promoting transversion RT mutation."; RL Proc. Natl. Acad. Sci. U.S.A. 115:4921-4926(2018). RN [13] RP FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT THR-634 (MICROBIAL RP INFECTION), AND CATALYTIC ACTIVITY. RX PubMed=31548683; DOI=10.1038/s41564-019-0529-z; RA Deutschmann J., Schneider A., Gruska I., Vetter B., Thomas D., RA Kiessling M., Wittmann S., Herrmann A., Schindler M., Milbradt J., RA Ferreiros N., Winkler T.H., Wiebusch L., Gramberg T.; RT "A viral kinase counteracts in vivo restriction of murine cytomegalovirus RT by SAMHD1."; RL Nat. Microbiol. 4:2273-2284(2019). RN [14] {ECO:0007744|PDB:6BRG, ECO:0007744|PDB:6BRH, ECO:0007744|PDB:6BRK} RP X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) IN COMPLEX WITH MAGNESIUM AND DGTP, RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, ACTIVITY REGULATION, AND MUTAGENESIS RP OF PHE-109; PHE-112 AND ARG-143. RX PubMed=29379009; DOI=10.1038/s41467-017-02783-8; RA Buzovetsky O., Tang C., Knecht K.M., Antonucci J.M., Wu L., Ji X., RA Xiong Y.; RT "The SAM domain of mouse SAMHD1 is critical for its activation and RT regulation."; RL Nat. Commun. 9:411-411(2018). CC -!- FUNCTION: [Isoform 1]: Protein that acts both as a host restriction CC factor involved in defense response to virus and as a regulator of DNA CC end resection at stalled replication forks (By similarity). Has CC deoxynucleoside triphosphate (dNTPase) activity, which is required to CC restrict infection by viruses: dNTPase activity reduces cellular dNTP CC levels to levels too low for retroviral reverse transcription to occur, CC blocking early-stage virus replication in dendritic and other myeloid CC cells (PubMed:23972988, PubMed:23872947, PubMed:26667483, CC PubMed:31548683, PubMed:29379009). Likewise, suppresses LINE-1 CC retrotransposon activity (PubMed:26667483). In addition to virus CC restriction, dNTPase activity acts as a regulator of DNA precursor CC pools by regulating dNTP pools (By similarity). Phosphorylation at Thr- CC 634 acts as a switch to control dNTPase-dependent and -independent CC functions: it inhibits dNTPase activity and ability to restrict CC infection by viruses, while it promotes DNA end resection at stalled CC replication forks (By similarity). Functions during S phase at stalled CC DNA replication forks to promote the resection of gapped or reversed CC forks: acts by stimulating the exonuclease activity of MRE11, CC activating the ATR-CHK1 pathway and allowing the forks to restart CC replication (By similarity). Its ability to promote degradation of CC nascent DNA at stalled replication forks is required to prevent CC induction of type I interferons, thereby preventing chronic CC inflammation (By similarity). Ability to promote DNA end resection at CC stalled replication forks is independent of dNTPase activity (By CC similarity). Enhances immunoglobulin hypermutation in B-lymphocytes by CC promoting transversion mutation (PubMed:29669924). CC {ECO:0000250|UniProtKB:Q9Y3Z3, ECO:0000269|PubMed:23872947, CC ECO:0000269|PubMed:23972988, ECO:0000269|PubMed:26667483, CC ECO:0000269|PubMed:29379009, ECO:0000269|PubMed:29669924, CC ECO:0000269|PubMed:31548683}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'- CC deoxyribonucleoside + H(+) + triphosphate; Xref=Rhea:RHEA:46148, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18036, CC ChEBI:CHEBI:18274, ChEBI:CHEBI:61560; CC Evidence={ECO:0000269|PubMed:29379009}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:Q9Y3Z3}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9Y3Z3}; CC -!- ACTIVITY REGULATION: Allosterically activated and regulated via the CC combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP): CC Allosteric site 1 binds GTP, while allosteric site 2 binds dNTP. CC Allosteric activation promotes the formation of highly active CC homotetramers. Isoform 1: Phosphorylation at Thr-634 impairs CC homotetramerization, thereby inhibiting dNTPase activity, leading to CC reduced ability to restrict infection by viruses. CC {ECO:0000305|PubMed:29379009}. CC -!- SUBUNIT: Homodimer; in absence of GTP and dNTP (By similarity). CC Homotetramer; in GTP- and dNTP-bound form (PubMed:29379009). Interacts CC with MRE11; leading to stimulate the exonuclease activity of MRE11 (By CC similarity). Interacts with RBBP8/CtIP (By similarity). Interacts with CC RBBP8/CtIP. Interacts (via its C-terminus) with CD81. CC {ECO:0000250|UniProtKB:Q9Y3Z3, ECO:0000269|PubMed:29379009}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y3Z3}. CC Chromosome {ECO:0000250|UniProtKB:Q9Y3Z3}. Note=Localizes to sites of CC DNA double-strand breaks in response to DNA damage. CC {ECO:0000250|UniProtKB:Q9Y3Z3}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q60710-1; Sequence=Displayed; CC Name=2; CC IsoId=Q60710-2; Sequence=VSP_059661; CC -!- INDUCTION: By interferon alpha, beta and gamma (IFN-alpha, IFN-beta and CC IFN-gamma). {ECO:0000269|PubMed:19525956}. CC -!- DOMAIN: In mouse, the SAM domain is required for deoxynucleoside CC triphosphate (dNTPase) activity and ability to restrict infection by CC viruses. It acts by capping allosteric sites. CC {ECO:0000269|PubMed:29379009}. CC -!- PTM: [Isoform 1]: Phosphorylation at Thr-634 by CDK1 acts as a switch CC to control deoxynucleoside triphosphate (dNTPase)-dependent and CC -independent functions (PubMed:26667483) (By similarity). CC Phosphorylation at Thr-634 takes place in cycling cells: it reduces the CC stability of the homotetramer, impairing the dNTPase activity and CC subsequent ability to restrict infection by viruses (Probable). It also CC inhibits ability to suppress LINE-1 retrotransposon activity CC (PubMed:26667483). In contrast, phosphorylation at Thr-634 promotes DNA CC end resection at stalled replication forks in response to DNA damage CC (By similarity). {ECO:0000250|UniProtKB:Q9Y3Z3, CC ECO:0000269|PubMed:26667483, ECO:0000305|PubMed:26667483}. CC -!- PTM: [Isoform 1]: (Microbial infection) Phosphorylation at Thr-634 by CC mouse cytomegalovirus kinase M97 leads to a reduced level of dNTP CC hydrolase activity and the loss of viral restriction. CC {ECO:0000269|PubMed:31548683}. CC -!- PTM: [Isoform 2]: Not phosphorylated by CDK1 at the C-terminus. CC {ECO:0000305}. CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile but show increased CC cellular dNTP concentrations and impaired ability to restrict CC retroviral replication in lymphocytes, macrophages and dendritic cells CC (PubMed:23972988). Mice also display interferon (IFN)-beta-dependent CC transcriptional up-regulation of type I IFN-inducible genes in various CC cell types indicative of spontaneous IFN production (PubMed:23972988, CC PubMed:23872947). In addition, the replication of mouse cytomegalovirus CC is significantly enhanced in mutant mice (PubMed:31548683). CC {ECO:0000269|PubMed:23872947, ECO:0000269|PubMed:23972988, CC ECO:0000269|PubMed:31548683}. CC -!- SIMILARITY: Belongs to the SAMHD1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA66219.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA66219.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAH12721.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH67198.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAC35801.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAE30313.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAE31954.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U15635; AAA66219.1; ALT_SEQ; mRNA. DR EMBL; AK054490; BAC35801.1; ALT_INIT; mRNA. DR EMBL; AK151335; BAE30313.1; ALT_INIT; mRNA. DR EMBL; AK153390; BAE31954.1; ALT_INIT; mRNA. DR EMBL; AL669828; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC012721; AAH12721.1; ALT_INIT; mRNA. DR EMBL; BC067198; AAH67198.1; ALT_INIT; mRNA. DR PIR; I49127; I49127. DR RefSeq; NP_001132992.1; NM_001139520.1. DR RefSeq; NP_061339.3; NM_018851.3. DR PDB; 6BRG; X-ray; 3.50 A; A/B/C/D=1-658. DR PDB; 6BRH; X-ray; 3.40 A; A/B=1-658. DR PDB; 6BRK; X-ray; 3.50 A; A=1-658. DR PDBsum; 6BRG; -. DR PDBsum; 6BRH; -. DR PDBsum; 6BRK; -. DR AlphaFoldDB; Q60710; -. DR SMR; Q60710; -. DR BioGRID; 207791; 17. DR IntAct; Q60710; 1. DR STRING; 10090.ENSMUSP00000059717; -. DR CarbonylDB; Q60710; -. DR GlyGen; Q60710; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q60710; -. DR PhosphoSitePlus; Q60710; -. DR SwissPalm; Q60710; -. DR EPD; Q60710; -. DR jPOST; Q60710; -. DR MaxQB; Q60710; -. DR PaxDb; 10090-ENSMUSP00000059717; -. DR PeptideAtlas; Q60710; -. DR ProteomicsDB; 256831; -. [Q60710-1] DR ProteomicsDB; 316795; -. DR ProteomicsDB; 318175; -. DR Pumba; Q60710; -. DR Antibodypedia; 26616; 567 antibodies from 36 providers. DR DNASU; 56045; -. DR Ensembl; ENSMUST00000057725.10; ENSMUSP00000059717.4; ENSMUSG00000027639.17. [Q60710-1] DR Ensembl; ENSMUST00000088523.11; ENSMUSP00000085880.5; ENSMUSG00000027639.17. [Q60710-2] DR GeneID; 56045; -. DR KEGG; mmu:56045; -. DR AGR; MGI:1927468; -. DR CTD; 25939; -. DR MGI; MGI:1927468; Samhd1. DR VEuPathDB; HostDB:ENSMUSG00000027639; -. DR eggNOG; KOG2681; Eukaryota. DR GeneTree; ENSGT00390000013867; -. DR InParanoid; Q60710; -. DR OMA; DYIARDC; -. DR OrthoDB; 5474479at2759; -. DR PhylomeDB; Q60710; -. DR TreeFam; TF316113; -. DR BRENDA; 3.1.5.B1; 3474. DR Reactome; R-MMU-8956319; Nucleotide catabolism. DR BioGRID-ORCS; 56045; 1 hit in 77 CRISPR screens. DR ChiTaRS; Samhd1; mouse. DR PRO; PR:Q60710; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; Q60710; Protein. DR Bgee; ENSMUSG00000027639; Expressed in granulocyte and 255 other cell types or tissues. DR ExpressionAtlas; Q60710; baseline and differential. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB. DR GO; GO:0097197; C:tetraspanin-enriched microdomain; ISO:MGI. DR GO; GO:0106375; F:deoxynucleoside triphosphate hydrolase activity; IEA:RHEA. DR GO; GO:0032567; F:dGTP binding; ISS:UniProtKB. DR GO; GO:0008832; F:dGTPase activity; IDA:UniProtKB. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0003676; F:nucleic acid binding; ISS:UniProtKB. DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB. DR GO; GO:0016793; F:triphosphoric monoester hydrolase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0046061; P:dATP catabolic process; ISS:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB. DR GO; GO:0009264; P:deoxyribonucleotide catabolic process; ISS:UniProtKB. DR GO; GO:0006203; P:dGTP catabolic process; ISS:UniProtKB. DR GO; GO:0006974; P:DNA damage response; ISS:UniProtKB. DR GO; GO:0110025; P:DNA strand resection involved in replication fork processing; ISS:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB. DR GO; GO:0045088; P:regulation of innate immune response; ISS:UniProtKB. DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IMP:UniProtKB. DR CDD; cd00077; HDc; 1. DR CDD; cd09508; SAM_HD; 1. DR Gene3D; 3.30.70.2760; -; 1. DR Gene3D; 1.10.3210.10; Hypothetical protein af1432; 1. DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1. DR InterPro; IPR003607; HD/PDEase_dom. DR InterPro; IPR006674; HD_domain. DR InterPro; IPR001660; SAM. DR InterPro; IPR013761; SAM/pointed_sf. DR PANTHER; PTHR11373; DEOXYNUCLEOSIDE TRIPHOSPHATE TRIPHOSPHOHYDROLASE; 1. DR PANTHER; PTHR11373:SF4; DEOXYNUCLEOSIDE TRIPHOSPHATE TRIPHOSPHOHYDROLASE SAMHD1; 1. DR Pfam; PF01966; HD; 1. DR Pfam; PF07647; SAM_2; 1. DR SMART; SM00471; HDc; 1. DR SMART; SM00454; SAM; 1. DR SUPFAM; SSF109604; HD-domain/PDEase-like; 1. DR SUPFAM; SSF47769; SAM/Pointed domain; 1. DR PROSITE; PS51831; HD; 1. DR PROSITE; PS50105; SAM_DOMAIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Allosteric enzyme; Alternative splicing; Antiviral defense; KW Chromosome; DNA damage; DNA repair; DNA replication; GTP-binding; KW Hydrolase; Immunity; Innate immunity; Isopeptide bond; Metal-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Ubl conjugation; Zinc. FT CHAIN 1..658 FT /note="Deoxynucleoside triphosphate triphosphohydrolase FT SAMHD1" FT /id="PRO_0000153733" FT DOMAIN 77..142 FT /note="SAM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184" FT DOMAIN 196..348 FT /note="HD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175" FT REGION 23..68 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 265 FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 148 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000305|PubMed:29379009, FT ECO:0007744|PDB:6BRH" FT BINDING 151 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 169..177 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000305|PubMed:29379009, FT ECO:0007744|PDB:6BRH" FT BINDING 181 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 196 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 199 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000305|PubMed:29379009, FT ECO:0007744|PDB:6BRH" FT BINDING 238 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000305|PubMed:29379009, FT ECO:0007744|PDB:6BRH" FT BINDING 239 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000305|PubMed:29379009, FT ECO:0007744|PDB:6BRH" FT BINDING 242 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 341..347 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 343 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000305|PubMed:29379009, FT ECO:0007744|PDB:6BRH" FT BINDING 347 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 351 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 365 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 395..397 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 401 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 409 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 413..418 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 419 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 420 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000305|PubMed:29379009, FT ECO:0007744|PDB:6BRH" FT BINDING 494 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000305|PubMed:29379009, FT ECO:0007744|PDB:6BRH" FT BINDING 498 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 565 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT MOD_RES 49 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 52 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 55 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 56 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 64 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT MOD_RES 125 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT MOD_RES 634 FT /note="(Microbial infection) Phosphothreonine" FT /evidence="ECO:0000269|PubMed:31548683" FT MOD_RES 634 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26667483, FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:19131326, FT ECO:0007744|PubMed:21183079" FT CROSSLNK 509 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT VAR_SEQ 625..658 FT /note="DGDIIAPLITPLKWNNKTSSCLQEVSKVKTCLKF -> QCGAGEMAEDPDSI FT PSTQQPHAAHNQL (in isoform 2)" FT /id="VSP_059661" FT MUTAGEN 109 FT /note="F->L: In LCH mutant; abolishes formation of the FT tetramer and deoxynucleoside triphosphate (dNTPase) FT activity; when associated with C-112 and H-143." FT /evidence="ECO:0000269|PubMed:29379009" FT MUTAGEN 112 FT /note="F->C: In LCH mutant; abolishes formation of the FT tetramer and deoxynucleoside triphosphate (dNTPase) FT activity; when associated with L-109 and H-143." FT /evidence="ECO:0000269|PubMed:29379009" FT MUTAGEN 143 FT /note="R->H: In LCH mutant; abolishes formation of the FT tetramer and deoxynucleoside triphosphate (dNTPase) FT activity; when associated with L-109 and C-112." FT /evidence="ECO:0000269|PubMed:29379009" FT MUTAGEN 634 FT /note="T->A,V: Increased ability to restrict LINE-1 FT retrotransposon activity." FT /evidence="ECO:0000269|PubMed:26667483" FT MUTAGEN 634 FT /note="T->E: Mimicks phosphorylation state, reduced ability FT to restrict LINE-1 retrotransposon activity." FT /evidence="ECO:0000269|PubMed:26667483" FT CONFLICT 371 FT /note="R -> L (in Ref. 2; BAE31954/BAE30313)" FT /evidence="ECO:0000305" FT HELIX 79..88 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 94..102 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 107..112 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 115..121 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 128..138 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 144..146 FT /evidence="ECO:0007829|PDB:6BRG" FT STRAND 148..152 FT /evidence="ECO:0007829|PDB:6BRH" FT TURN 153..155 FT /evidence="ECO:0007829|PDB:6BRH" FT STRAND 156..160 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 162..168 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 171..174 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 175..178 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 183..187 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 196..217 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 219..221 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 225..236 FT /evidence="ECO:0007829|PDB:6BRH" FT TURN 237..241 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 247..251 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 253..257 FT /evidence="ECO:0007829|PDB:6BRH" FT STRAND 259..261 FT /evidence="ECO:0007829|PDB:6BRK" FT HELIX 265..279 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 282..288 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 293..305 FT /evidence="ECO:0007829|PDB:6BRH" FT STRAND 320..322 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 324..331 FT /evidence="ECO:0007829|PDB:6BRH" FT TURN 336..339 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 342..355 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 363..368 FT /evidence="ECO:0007829|PDB:6BRH" FT STRAND 370..378 FT /evidence="ECO:0007829|PDB:6BRH" FT STRAND 386..394 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 396..398 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 399..415 FT /evidence="ECO:0007829|PDB:6BRH" FT TURN 416..418 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 420..436 FT /evidence="ECO:0007829|PDB:6BRH" FT TURN 437..439 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 445..447 FT /evidence="ECO:0007829|PDB:6BRH" FT TURN 452..454 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 455..457 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 459..462 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 469..475 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 479..481 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 482..492 FT /evidence="ECO:0007829|PDB:6BRH" FT STRAND 498..503 FT /evidence="ECO:0007829|PDB:6BRH" FT STRAND 505..508 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 514..517 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 518..524 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 537..539 FT /evidence="ECO:0007829|PDB:6BRH" FT STRAND 540..546 FT /evidence="ECO:0007829|PDB:6BRH" FT STRAND 590..597 FT /evidence="ECO:0007829|PDB:6BRH" FT HELIX 601..617 FT /evidence="ECO:0007829|PDB:6BRH" SQ SEQUENCE 658 AA; 75893 MW; 8ED07CE9EB6239D6 CRC64; MDSLLGCGVS AAAREPVPRY LTSQPRVSEV AMQSAPLEQP AKRPRCDGSP RTPPSTPPAT ANLSADDDFQ NTDLRTWEPE DVCSFLENRG FREKKVLDIF RDNKIAGSFL PFLDEDRLED LGVSSLEERK KMIECIQQLS QSRIDLMKVF NDPIHGHIEF HPLLIRIIDT PQFQRLRYIK QLGGGYYVFP GASHNRFEHS LGVGYLAGCL VRALAEKQPE LQISERDILC VQIAGLCHDL GHGPFSHMFD GRFIPRARPE KKWKHEQGSI EMFEHLVNSN ELKLVMKNYG LVPEEDITFI KEQIMGPPIT PVKDSLWPYK GRPATKSFLY EIVSNKRNGI DVDKWDYFAR DCHHLGIQNN FDYKRFIKFA RICEVEYKVK EDKTYIRKVK HICSREKEVG NLYDMFHTRN CLHRRAYQHK ISNLIDIMIT DAFLKADPYV EITGTAGKKF RISTAIDDME AFTKLTDNIF LEVLHSTDPQ LSEAQSILRN IECRNLYKYL GETQPKREKI RKEEYERLPQ EVAKAKPEKA PDVELKAEDF IVDVINVDYG MEDKNPIDRV HFYCKSNSKQ AVRINKEQVS QLLPEKFAEQ LIRVYCKKKD GKSLDAAGKH FVQWCALRDF TKPQDGDIIA PLITPLKWNN KTSSCLQEVS KVKTCLKF //