SAMH1_MOUSE
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 03-AUG-2022, entry version 177.
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, Pancreas,
RC 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};
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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 iPTMnet; Q60710; -.
DR PhosphoSitePlus; Q60710; -.
DR SwissPalm; Q60710; -.
DR EPD; Q60710; -.
DR jPOST; Q60710; -.
DR MaxQB; Q60710; -.
DR PaxDb; Q60710; -.
DR PeptideAtlas; Q60710; -.
DR PRIDE; Q60710; -.
DR ProteomicsDB; 256831; -. [Q60710-1]
DR ProteomicsDB; 316795; -.
DR ProteomicsDB; 318175; -.
DR Antibodypedia; 26616; 487 antibodies from 36 providers.
DR DNASU; 56045; -.
DR Ensembl; ENSMUST00000057725; ENSMUSP00000059717; ENSMUSG00000027639. [Q60710-1]
DR Ensembl; ENSMUST00000088523; ENSMUSP00000085880; ENSMUSG00000027639. [Q60710-2]
DR GeneID; 56045; -.
DR KEGG; mmu:56045; -.
DR CTD; 25939; -.
DR MGI; MGI:1927468; Samhd1.
DR VEuPathDB; HostDB:ENSMUSG00000027639; -.
DR eggNOG; KOG2681; Eukaryota.
DR GeneTree; ENSGT00390000013867; -.
DR InParanoid; Q60710; -.
DR OMA; GPEQVCF; -.
DR OrthoDB; 835545at2759; -.
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 72 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 251 other 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:0004540; F:ribonuclease activity; 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:0006974; P:cellular response to DNA damage stimulus; 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: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 Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR006674; HD_domain.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR Pfam; PF01966; HD; 1.
DR Pfam; PF07647; SAM_2; 1.
DR SMART; SM00471; HDc; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 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
