SAMH1_HUMAN
ID SAMH1_HUMAN Reviewed; 626 AA.
AC Q9Y3Z3; B4E2A5; E1P5V2; Q5JXG8; Q8N491; Q9H004; Q9H005; Q9H3U9;
DT 13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-2002, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 {ECO:0000305};
DE Short=dNTPase {ECO:0000305};
DE EC=3.1.5.- {ECO:0000269|PubMed:22056990, ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:26101257, ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:31291580};
DE AltName: Full=Dendritic cell-derived IFNG-induced protein {ECO:0000303|PubMed:11064105};
DE Short=DCIP {ECO:0000303|PubMed:11064105};
DE AltName: Full=Monocyte protein 5 {ECO:0000303|Ref.2};
DE Short=MOP-5 {ECO:0000303|Ref.2};
DE AltName: Full=SAM domain and HD domain-containing protein 1 {ECO:0000305};
DE Short=hSAMHD1 {ECO:0000303|PubMed:29379009};
GN Name=SAMHD1 {ECO:0000312|HGNC:HGNC:15925};
GN Synonyms=MOP5 {ECO:0000303|Ref.2};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Brain;
RX PubMed=11064105; DOI=10.1016/s0165-2478(00)00276-5;
RA Li N., Zhang W., Cao X.;
RT "Identification of human homologue of mouse IFN-gamma induced protein from
RT human dendritic cells.";
RL Immunol. Lett. 74:221-224(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Platelet;
RA Takayama K., Yoshimoto M.;
RT "Molecular and biological characterization of a novel monocyte protein,
RT MOP-5.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [8]
RP PROTEIN SEQUENCE OF 1-10, ACETYLATION AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=T-cell;
RA Bienvenut W.V., Kanor S., Tissot J.-D., Quadroni M.;
RL Submitted (MAY-2006) to UniProtKB.
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-592, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-592, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-592, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP INDUCTION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18546154; DOI=10.1002/pmic.200700954;
RA Liao W., Bao Z., Cheng C., Mok Y.-K., Wong W.S.;
RT "Dendritic cell-derived interferon-gamma-induced protein mediates tumor
RT necrosis factor-alpha stimulation of human lung fibroblasts.";
RL Proteomics 8:2640-2650(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-592, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP INVOLVEMENT IN AGS5.
RX PubMed=20842748; DOI=10.1002/humu.21357;
RA Thiele H., du Moulin M., Barczyk K., George C., Schwindt W., Nurnberg G.,
RA Frosch M., Kurlemann G., Roth J., Nurnberg P., Rutsch F.;
RT "Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutieres
RT syndrome caused by the Arg164X mutation in SAMHD1 are associated with
RT altered cytokine expression.";
RL Hum. Mutat. 31:E1836-E1850(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-592, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP FUNCTION, INTERACTION WITH HIV-2 VIRUS PROTEIN VPX (MICROBIAL INFECTION),
RP UBIQUITINATION (MICROBIAL INFECTION), AND MUTAGENESIS OF 206-HIS-ASP-207.
RX PubMed=21613998; DOI=10.1038/nature10117;
RA Laguette N., Sobhian B., Casartelli N., Ringeard M., Chable-Bessia C.,
RA Segeral E., Yatim A., Emiliani S., Schwartz O., Benkirane M.;
RT "SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction
RT factor counteracted by Vpx.";
RL Nature 474:654-657(2011).
RN [19]
RP FUNCTION, INTERACTION WITH HIV-2 VIRUS PROTEIN VPX (MICROBIAL INFECTION),
RP AND UBIQUITINATION (MICROBIAL INFECTION).
RX PubMed=21720370; DOI=10.1038/nature10195;
RA Hrecka K., Hao C., Gierszewska M., Swanson S.K., Kesik-Brodacka M.,
RA Srivastava S., Florens L., Washburn M.P., Skowronski J.;
RT "Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the
RT SAMHD1 protein.";
RL Nature 474:658-661(2011).
RN [20]
RP SUBCELLULAR LOCATION, AND ALTERNATIVE SPLICING (ISOFORMS 3 AND 4).
RX PubMed=23092512; DOI=10.1186/1742-4690-9-86;
RA Welbourn S., Miyagi E., White T.E., Diaz-Griffero F., Strebel K.;
RT "Identification and characterization of naturally occurring splice variants
RT of SAMHD1.";
RL Retrovirology 9:86-86(2012).
RN [21]
RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT THR-592, AND MUTAGENESIS
RP OF 206-HIS-ASP-207 AND THR-592.
RX PubMed=23602554; DOI=10.1016/j.celrep.2013.03.017;
RA Cribier A., Descours B., Valadao A.L., Laguette N., Benkirane M.;
RT "Phosphorylation of SAMHD1 by cyclin A2/CDK1 regulates its restriction
RT activity toward HIV-1.";
RL Cell Rep. 3:1036-1043(2013).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS AGS5
RP PRO-123; HIS-143; GLN-145; TYR-167; ASN-201; SER-209; VAL-254 AND HIS-290.
RX PubMed=24035396; DOI=10.1016/j.celrep.2013.08.019;
RA Zhao K., Du J., Han X., Goodier J.L., Li P., Zhou X., Wei W., Evans S.L.,
RA Li L., Zhang W., Cheung L.E., Wang G., Kazazian H.H. Jr., Yu X.F.;
RT "Modulation of LINE-1 and Alu/SVA retrotransposition by Aicardi-Goutieres
RT syndrome-related SAMHD1.";
RL Cell Rep. 4:1108-1115(2013).
RN [23]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, ACTIVITY REGULATION, PHOSPHORYLATION
RP AT THR-592, AND MUTAGENESIS OF THR-592 AND PRO-593.
RX PubMed=23601106; DOI=10.1016/j.chom.2013.03.005;
RA White T.E., Brandariz-Nunez A., Valle-Casuso J.C., Amie S., Nguyen L.A.,
RA Kim B., Tuzova M., Diaz-Griffero F.;
RT "The retroviral restriction ability of SAMHD1, but not its deoxynucleotide
RT triphosphohydrolase activity, is regulated by phosphorylation.";
RL Cell Host Microbe 13:441-451(2013).
RN [24]
RP FUNCTION.
RX PubMed=23364794; DOI=10.1074/jbc.m112.431148;
RA Beloglazova N., Flick R., Tchigvintsev A., Brown G., Popovic A., Nocek B.,
RA Yakunin A.F.;
RT "Nuclease activity of the human SAMHD1 protein implicated in the Aicardi-
RT Goutieres syndrome and HIV-1 restriction.";
RL J. Biol. Chem. 288:8101-8110(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-33; SER-93 AND THR-592, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23858451; DOI=10.1073/pnas.1312033110;
RA Franzolin E., Pontarin G., Rampazzo C., Miazzi C., Ferraro P., Palumbo E.,
RA Reichard P., Bianchi V.;
RT "The deoxynucleotide triphosphohydrolase SAMHD1 is a major regulator of DNA
RT precursor pools in mammalian cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:14272-14277(2013).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-33 AND THR-592, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [28]
RP FUNCTION, AND MUTAGENESIS OF ASP-137; ASP-207 AND ASP-311.
RX PubMed=25038827; DOI=10.1038/nm.3626;
RA Ryoo J., Choi J., Oh C., Kim S., Seo M., Kim S.Y., Seo D., Kim J.,
RA White T.E., Brandariz-Nunez A., Diaz-Griffero F., Yun C.H.,
RA Hollenbaugh J.A., Kim B., Baek D., Ahn K.;
RT "The ribonuclease activity of SAMHD1 is required for HIV-1 restriction.";
RL Nat. Med. 20:936-941(2014).
RN [29]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 206-HIS-ASP-207; ASP-207;
RP ARG-451; GLN-548 AND THR-592.
RX PubMed=26101257; DOI=10.1093/nar/gkv633;
RA Seamon K.J., Sun Z., Shlyakhtenko L.S., Lyubchenko Y.L., Stivers J.T.;
RT "SAMHD1 is a single-stranded nucleic acid binding protein with no active
RT site-associated nuclease activity.";
RL Nucleic Acids Res. 43:6486-6499(2015).
RN [30]
RP FUNCTION.
RX PubMed=27477283; DOI=10.1016/j.celrep.2016.07.002;
RA Maelfait J., Bridgeman A., Benlahrech A., Cursi C., Rehwinkel J.;
RT "Restriction by SAMHD1 limits cGAS/STING-dependent innate and adaptive
RT immune responses to HIV-1.";
RL Cell Rep. 16:1492-1501(2016).
RN [31]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MRE11 AND RBBP8, AND
RP MUTAGENESIS OF 206-HIS-ASP-207.
RX PubMed=28834754; DOI=10.1016/j.celrep.2017.08.008;
RA Daddacha W., Koyen A.E., Bastien A.J., Head P.E., Dhere V.R., Nabeta G.N.,
RA Connolly E.C., Werner E., Madden M.Z., Daly M.B., Minten E.V., Whelan D.R.,
RA Schlafstein A.J., Zhang H., Anand R., Doronio C., Withers A.E., Shepard C.,
RA Sundaram R.K., Deng X., Dynan W.S., Wang Y., Bindra R.S., Cejka P.,
RA Rothenberg E., Doetsch P.W., Kim B., Yu D.S.;
RT "SAMHD1 promotes DNA end resection to facilitate DNA repair by homologous
RT recombination.";
RL Cell Rep. 20:1921-1935(2017).
RN [32]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS AGS5
RP PRO-123; CYS-143; HIS-143; GLN-145; TYR-167; ASN-201; SER-209; VAL-254;
RP HIS-290; SER-369; VAL-385 AND THR-448, AND MUTAGENESIS OF ARG-226; ASP-311
RP AND GLN-548.
RX PubMed=28229507; DOI=10.1002/humu.23201;
RA White T.E., Brandariz-Nunez A., Martinez-Lopez A., Knowlton C., Lenzi G.,
RA Kim B., Ivanov D., Diaz-Griffero F.;
RT "A SAMHD1 mutation associated with Aicardi-Goutieres Syndrome uncouples the
RT ability of SAMHD1 to restrict HIV-1 from its ability to downmodulate type I
RT interferon in humans.";
RL Hum. Mutat. 38:658-668(2017).
RN [33]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CD81.
RX PubMed=28871089; DOI=10.1038/s41564-017-0019-0;
RA Rocha-Perugini V., Suarez H., Alvarez S., Lopez-Martin S., Lenzi G.M.,
RA Vences-Catalan F., Levy S., Kim B., Munoz-Fernandez M.A.,
RA Sanchez-Madrid F., Yanez-Mo M.;
RT "CD81 association with SAMHD1 enhances HIV-1 reverse transcription by
RT increasing dNTP levels.";
RL Nat. Microbiol. 2:1513-1522(2017).
RN [34]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-467; LYS-469; LYS-492 AND
RP LYS-622, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [35]
RP FUNCTION, ACTIVITY REGULATION, AND PHOSPHORYLATION AT THR-592.
RX PubMed=29610582; DOI=10.1186/s13100-018-0116-5;
RA Herrmann A., Wittmann S., Thomas D., Shepard C.N., Kim B., Ferreiros N.,
RA Gramberg T.;
RT "The SAMHD1-mediated block of LINE-1 retroelements is regulated by
RT phosphorylation.";
RL Mob. DNA 9:11-11(2018).
RN [36]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, INTERACTION WITH
RP MRE11, PHOSPHORYLATION AT THR-592, MUTAGENESIS OF LYS-312; TYR-315 AND
RP THR-592, VARIANT AGS5 548-GLN--MET-626 DEL, AND CHARACTERIZATION OF VARIANT
RP AGS5 548-GLN--MET-626 DEL.
RX PubMed=29670289; DOI=10.1038/s41586-018-0050-1;
RA Coquel F., Silva M.J., Techer H., Zadorozhny K., Sharma S.,
RA Nieminuszczy J., Mettling C., Dardillac E., Barthe A., Schmitz A.L.,
RA Promonet A., Cribier A., Sarrazin A., Niedzwiedz W., Lopez B., Costanzo V.,
RA Krejci L., Chabes A., Benkirane M., Lin Y.L., Pasero P.;
RT "SAMHD1 acts at stalled replication forks to prevent interferon
RT induction.";
RL Nature 557:57-61(2018).
RN [37]
RP DOMAIN, AND MUTAGENESIS OF LEU-77; CYS-80 AND HIS-111.
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).
RN [38]
RP FUNCTION, CATALYTIC ACTIVITY, AND PHOSPHORYLATION AT THR-592 (MICROBIAL
RP INFECTION).
RX PubMed=31291580; DOI=10.1016/j.celrep.2019.04.020;
RA Zhang K., Lv D.W., Li R.;
RT "Conserved Herpesvirus Protein Kinases Target SAMHD1 to Facilitate Virus
RT Replication.";
RL Cell Rep. 28:449-459(2019).
RN [39]
RP FUNCTION, PHOSPHORYLATION AT THR-592 (MICROBIAL INFECTION), AND MUTAGENESIS
RP OF THR-592.
RX PubMed=31548682; DOI=10.1038/s41564-019-0557-8;
RA Businger R., Deutschmann J., Gruska I., Milbradt J., Wiebusch L.,
RA Gramberg T., Schindler M.;
RT "Human cytomegalovirus overcomes SAMHD1 restriction in macrophages via
RT pUL97.";
RL Nat. Microbiol. 4:2260-2272(2019).
RN [40]
RP STRUCTURE BY NMR OF 23-118.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the N-terminal SAM-domain of the SAM domain and HD
RT domain containing protein 1 (dendritic cell-derived IFNG-induced protein)
RT (DCIP) (monocyte protein 5) (MOP-5).";
RL Submitted (JUL-2007) to the PDB data bank.
RN [41]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 120-626, CATALYTIC ACTIVITY,
RP ZINC-BINDING SITES, SUBSTRATE-BINDING SITES, ACTIVE SITE, ACTIVITY
RP REGULATION, UBIQUITINATION (MICROBIAL INFECTION), AND FUNCTION.
RX PubMed=22056990; DOI=10.1038/nature10623;
RA Goldstone D.C., Ennis-Adeniran V., Hedden J.J., Groom H.C., Rice G.I.,
RA Christodoulou E., Walker P.A., Kelly G., Haire L.F., Yap M.W.,
RA de Carvalho L.P., Stoye J.P., Crow Y.J., Taylor I.A., Webb M.;
RT "HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate
RT triphosphohydrolase.";
RL Nature 480:379-382(2011).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 109-626 IN COMPLEX WITH ATP; GTP
RP AND ZINC, SUBUNIT, ACTIVITY REGULATION, CATALYTIC ACTIVITY, AND MUTAGENESIS
RP OF ASP-137; GLN-142; ARG-145; ARG-333 AND ARG-451.
RX PubMed=24217394; DOI=10.1038/ncomms3722;
RA Zhu C., Gao W., Zhao K., Qin X., Zhang Y., Peng X., Zhang L., Dong Y.,
RA Zhang W., Li P., Wei W., Gong Y., Yu X.F.;
RT "Structural insight into dGTP-dependent activation of tetrameric SAMHD1
RT deoxynucleoside triphosphate triphosphohydrolase.";
RL Nat. Commun. 4:2722-2722(2013).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 113-626 IN COMPLEX WITH GTP AND
RP ZINC, SUBUNIT, ACTIVITY REGULATION, MUTAGENESIS OF GLN-149;
RP 206-HIS-ASP-207; LYS-312; TYR-315; ASP-319; ASP-330; ARG-333; ARG-352;
RP ASN-358; ASP-361; HIS-364; ARG-366; HIS-370; TYR-374; 376-HIS-LYS-377;
RP LYS-534; VAL-537 AND LEU-540, AND COFACTOR.
RX PubMed=24141705; DOI=10.1038/nsmb.2692;
RA Ji X., Wu Y., Yan J., Mehrens J., Yang H., DeLucia M., Hao C.,
RA Gronenborn A.M., Skowronski J., Ahn J., Xiong Y.;
RT "Mechanism of allosteric activation of SAMHD1 by dGTP.";
RL Nat. Struct. Mol. Biol. 20:1304-1309(2013).
RN [44] {ECO:0007744|PDB:4QFX, ECO:0007744|PDB:4QFY, ECO:0007744|PDB:4QFZ, ECO:0007744|PDB:4QG0, ECO:0007744|PDB:4QG1, ECO:0007744|PDB:4QG2, ECO:0007744|PDB:4QG4}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 113-626 IN COMPLEX WITH GTP AND
RP ZINC, COFACTOR, SUBUNIT, ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-137;
RP GLN-142; ARG-145; GLN-149; HIS-210; HIS-215; HIS-233; ASP-330; ASN-358 AND
RP GLN-375.
RX PubMed=25288794; DOI=10.1074/jbc.m114.591958;
RA Koharudin L.M., Wu Y., DeLucia M., Mehrens J., Gronenborn A.M., Ahn J.;
RT "Structural basis of allosteric activation of sterile alpha motif and
RT histidine-aspartate domain-containing protein 1 (SAMHD1) by nucleoside
RT triphosphates.";
RL J. Biol. Chem. 289:32617-32627(2014).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.47 ANGSTROMS) OF 582-626 IN COMPLEX WITH DCAF1 AND
RP SIMIAN IMMUNODEFICIENCY VIRUS PROTEIN VPX, UBIQUITINATION (MICROBIAL
RP INFECTION), FUNCTION, AND MUTAGENESIS OF ARG-609; ARG-617 AND LYS-622.
RX PubMed=24336198; DOI=10.1038/nature12815;
RA Schwefel D., Groom H.C., Boucherit V.C., Christodoulou E., Walker P.A.,
RA Stoye J.P., Bishop K.N., Taylor I.A.;
RT "Structural basis of lentiviral subversion of a cellular protein
RT degradation pathway.";
RL Nature 505:234-238(2014).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 113-626 IN COMPLEX WITH GTP,
RP SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=25267621; DOI=10.1073/pnas.1412289111;
RA Ji X., Tang C., Zhao Q., Wang W., Xiong Y.;
RT "Structural basis of cellular dNTP regulation by SAMHD1.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E4305-E4314(2014).
RN [47] {ECO:0007744|PDB:4RXO, ECO:0007744|PDB:4RXP, ECO:0007744|PDB:4RXQ, ECO:0007744|PDB:4RXR, ECO:0007744|PDB:4RXS}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 109-626 IN COMPLEX WITH GTP AND
RP ZINC, COFACTOR, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=25760601; DOI=10.1107/s1399004714027527;
RA Zhu C.F., Wei W., Peng X., Dong Y.H., Gong Y., Yu X.F.;
RT "The mechanism of substrate-controlled allosteric regulation of SAMHD1
RT activated by GTP.";
RL Acta Crystallogr. D 71:516-524(2015).
RN [48] {ECO:0007744|PDB:4ZWE, ECO:0007744|PDB:4ZWG}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 113-626 OF MUTANT GLU-592 IN
RP COMPLEX WITH GTP, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, ACTIVITY
RP REGULATION, PHOSPHORYLATION AT THR-592, AND MUTAGENESIS OF THR-592.
RX PubMed=26294762; DOI=10.1074/jbc.m115.677435;
RA Tang C., Ji X., Wu L., Xiong Y.;
RT "Impaired dNTPase activity of SAMHD1 by phosphomimetic mutation of Thr-
RT 592.";
RL J. Biol. Chem. 290:26352-26359(2015).
RN [49] {ECO:0007744|PDB:5AO0, ECO:0007744|PDB:5AO1, ECO:0007744|PDB:5AO2, ECO:0007744|PDB:5AO3, ECO:0007744|PDB:5AO4}
RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 115-583 OF MUTANT ALA-164 IN
RP COMPLEX WITH GTP AND IRON, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT,
RP ACTIVITY REGULATION, PHOSPHORYLATION AT THR-592, AND MUTAGENESIS OF
RP ARG-143; ARG-145; ARG-164; HIS-167; HIS-206; ASP-207; HIS-233; ASP-311;
RP TYR-315; HIS-321; ARG-372 AND THR-592.
RX PubMed=26431200; DOI=10.1371/journal.ppat.1005194;
RA Arnold L.H., Groom H.C., Kunzelmann S., Schwefel D., Caswell S.J.,
RA Ordonez P., Mann M.C., Rueschenbaum S., Goldstone D.C., Pennell S.,
RA Howell S.A., Stoye J.P., Webb M., Taylor I.A., Bishop K.N.;
RT "Phospho-dependent Regulation of SAMHD1 Oligomerisation Couples Catalysis
RT and Restriction.";
RL PLoS Pathog. 11:E1005194-E1005194(2015).
RN [50]
RP VARIANTS AGS5 PRO-123; CYS-143; HIS-143; GLN-145; ASN-201; SER-209;
RP VAL-254; SER-369 AND VAL-385, FUNCTION, AND SUBCELLULAR LOCATION.
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 [51]
RP VARIANTS AGS5 TYR-167 AND HIS-290.
RX PubMed=20131292; DOI=10.1002/art.27367;
RA Ramantani G., Kohlhase J., Hertzberg C., Innes A.M., Engel K., Hunger S.,
RA Borozdin W., Mah J.K., Ungerath K., Walkenhorst H., Richardt H.H.,
RA Buckard J., Bevot A., Siegel C., von Stuelpnagel C., Ikonomidou C.,
RA Thomas K., Proud V., Niemann F., Wieczorek D., Haeusler M., Niggemann P.,
RA Baltaci V., Conrad K., Lebon P., Lee-Kirsch M.A.;
RT "Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-
RT Goutieres syndrome.";
RL Arthritis Rheum. 62:1469-1477(2010).
RN [52]
RP VARIANT CHBL2 ASN-201.
RX PubMed=21204240; DOI=10.1002/ajmg.a.33778;
RA Ravenscroft J.C., Suri M., Rice G.I., Szynkiewicz M., Crow Y.J.;
RT "Autosomal dominant inheritance of a heterozygous mutation in SAMHD1
RT causing familial chilblain lupus.";
RL Am. J. Med. Genet. A 155:235-237(2011).
RN [53]
RP VARIANTS AGS5 120-ASP--HIS-123 DEL; PRO-123; HIS-143; ASN-201; VAL-254;
RP VAL-385 AND THR-448.
RX PubMed=24183309; DOI=10.1016/s1474-4422(13)70258-8;
RA Rice G.I., Forte G.M., Szynkiewicz M., Chase D.S., Aeby A.,
RA Abdel-Hamid M.S., Ackroyd S., Allcock R., Bailey K.M., Balottin U.,
RA Barnerias C., Bernard G., Bodemer C., Botella M.P., Cereda C.,
RA Chandler K.E., Dabydeen L., Dale R.C., De Laet C., De Goede C.G.,
RA Del Toro M., Effat L., Enamorado N.N., Fazzi E., Gener B., Haldre M.,
RA Lin J.P., Livingston J.H., Lourenco C.M., Marques W. Jr., Oades P.,
RA Peterson P., Rasmussen M., Roubertie A., Schmidt J.L., Shalev S.A.,
RA Simon R., Spiegel R., Swoboda K.J., Temtamy S.A., Vassallo G., Vilain C.N.,
RA Vogt J., Wermenbol V., Whitehouse W.P., Soler D., Olivieri I., Orcesi S.,
RA Aglan M.S., Zaki M.S., Abdel-Salam G.M., Vanderver A., Kisand K.,
RA Rozenberg F., Lebon P., Crow Y.J.;
RT "Assessment of interferon-related biomarkers in Aicardi-Goutieres syndrome
RT associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1,
RT and ADAR: a case-control study.";
RL Lancet Neurol. 12:1159-1169(2013).
CC -!- FUNCTION: Protein that acts both as a host restriction factor involved
CC in defense response to virus and as a regulator of DNA end resection at
CC stalled replication forks (PubMed:19525956, PubMed:21613998,
CC PubMed:21720370, PubMed:23602554, PubMed:23601106, PubMed:22056990,
CC PubMed:24336198, PubMed:26294762, PubMed:26431200, PubMed:28229507,
CC PubMed:28834754, PubMed:29670289). Has deoxynucleoside triphosphate
CC (dNTPase) activity, which is required to restrict infection by viruses,
CC such as HIV-1: dNTPase activity reduces cellular dNTP levels to levels
CC too low for retroviral reverse transcription to occur, blocking early-
CC stage virus replication in dendritic and other myeloid cells
CC (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:23602554,
CC PubMed:23601106, PubMed:23364794, PubMed:25038827, PubMed:26101257,
CC PubMed:22056990, PubMed:24336198, PubMed:28229507, PubMed:26294762,
CC PubMed:26431200). Likewise, suppresses LINE-1 retrotransposon activity
CC (PubMed:24035396, PubMed:29610582, PubMed:24217394). Not able to
CC restrict infection by HIV-2 virus; because restriction activity is
CC counteracted by HIV-2 viral protein Vpx (PubMed:21613998,
CC PubMed:21720370). In addition to virus restriction, dNTPase activity
CC acts as a regulator of DNA precursor pools by regulating dNTP pools
CC (PubMed:23858451). Phosphorylation at Thr-592 acts as a switch to
CC control dNTPase-dependent and -independent functions: it inhibits
CC dNTPase activity and ability to restrict infection by viruses, while it
CC promotes DNA end resection at stalled replication forks
CC (PubMed:23602554, PubMed:23601106, PubMed:29610582, PubMed:29670289).
CC Functions during S phase at stalled DNA replication forks to promote
CC the resection of gapped or reversed forks: acts by stimulating the
CC exonuclease activity of MRE11, activating the ATR-CHK1 pathway and
CC allowing the forks to restart replication (PubMed:29670289). Its
CC ability to promote degradation of nascent DNA at stalled replication
CC forks is required to prevent induction of type I interferons, thereby
CC preventing chronic inflammation (PubMed:27477283, PubMed:29670289).
CC Ability to promote DNA end resection at stalled replication forks is
CC independent of dNTPase activity (PubMed:29670289). Enhances
CC immunoglobulin hypermutation in B-lymphocytes by promoting transversion
CC mutation (By similarity). {ECO:0000250|UniProtKB:Q60710,
CC ECO:0000269|PubMed:19525956, ECO:0000269|PubMed:21613998,
CC ECO:0000269|PubMed:21720370, ECO:0000269|PubMed:22056990,
CC ECO:0000269|PubMed:23364794, ECO:0000269|PubMed:23601106,
CC ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:23858451,
CC ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:24217394,
CC ECO:0000269|PubMed:24336198, ECO:0000269|PubMed:25038827,
CC ECO:0000269|PubMed:26101257, ECO:0000269|PubMed:26294762,
CC ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:27477283,
CC ECO:0000269|PubMed:28229507, ECO:0000269|PubMed:28834754,
CC ECO:0000269|PubMed:29610582, ECO:0000269|PubMed:29670289}.
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:22056990, ECO:0000269|PubMed:23601106,
CC ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:26101257,
CC ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:24141705, ECO:0000269|PubMed:24217394,
CC ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
CC ECO:0000269|PubMed:26431200};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:24141705,
CC ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25288794,
CC ECO:0000269|PubMed:25760601, ECO:0000269|PubMed:26431200};
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 (PubMed:25288794, PubMed:25267621, PubMed:25760601). Allosteric
CC activation promotes the formation of highly active homotetramers
CC (PubMed:22056990, PubMed:24141705, PubMed:24217394, PubMed:25288794,
CC PubMed:25267621, PubMed:25760601). Phosphorylation at Thr-592 impairs
CC homotetramerization, thereby inhibiting dNTPase activity, leading to
CC reduced ability to restrict infection by viruses (PubMed:23602554,
CC PubMed:23601106, PubMed:26294762, PubMed:26431200, PubMed:29610582,
CC PubMed:29670289). {ECO:0000269|PubMed:22056990,
CC ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554,
CC ECO:0000269|PubMed:24141705, ECO:0000269|PubMed:24217394,
CC ECO:0000269|PubMed:25267621, ECO:0000269|PubMed:25288794,
CC ECO:0000269|PubMed:25760601, ECO:0000269|PubMed:26294762,
CC ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:29610582,
CC ECO:0000269|PubMed:29670289}.
CC -!- SUBUNIT: Homodimer; in absence of GTP and dNTP (PubMed:24141705,
CC PubMed:24217394, PubMed:28229507, PubMed:25760601). Homotetramer; in
CC GTP- and dNTP-bound form (PubMed:23601106, PubMed:26101257,
CC PubMed:24141705, PubMed:24217394, PubMed:28229507, PubMed:26294762,
CC PubMed:26431200, PubMed:25288794, PubMed:25267621, PubMed:25760601).
CC Interacts with MRE11; leading to stimulate the exonuclease activity of
CC MRE11 (PubMed:28834754, PubMed:29670289). Interacts with RBBP8/CtIP
CC (PubMed:28834754). Interacts (via its C-terminus) with CD81.
CC {ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:24141705,
CC ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
CC ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
CC ECO:0000269|PubMed:26101257, ECO:0000269|PubMed:26294762,
CC ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:28229507,
CC ECO:0000269|PubMed:28834754, ECO:0000269|PubMed:28871089,
CC ECO:0000269|PubMed:29670289}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-2 viral protein Vpx;
CC promoting interaction with a E3 ubiquitin-protein ligase complex
CC containing DCAF1, leading to subsequent ubiquitination and degradation
CC of SAMHD1. {ECO:0000269|PubMed:21613998, ECO:0000269|PubMed:21720370,
CC ECO:0000269|PubMed:24336198}.
CC -!- INTERACTION:
CC Q9Y3Z3; Q08380: LGALS3BP; NbExp=2; IntAct=EBI-1054601, EBI-354956;
CC Q9Y3Z3; Q9Y3Z3: SAMHD1; NbExp=7; IntAct=EBI-1054601, EBI-1054601;
CC Q9Y3Z3; P58753: TIRAP; NbExp=2; IntAct=EBI-1054601, EBI-528644;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19525956,
CC ECO:0000269|PubMed:23092512, ECO:0000269|PubMed:23858451,
CC ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:28229507,
CC ECO:0000269|PubMed:28871089}. Chromosome {ECO:0000269|PubMed:28834754}.
CC Note=Localizes to sites of DNA double-strand breaks in response to DNA
CC damage. {ECO:0000269|PubMed:28834754}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y3Z3-1; Sequence=Displayed;
CC Name=3; Synonyms=delta8-9;
CC IsoId=Q9Y3Z3-3; Sequence=VSP_046561;
CC Name=4; Synonyms=delta14;
CC IsoId=Q9Y3Z3-4; Sequence=VSP_046562;
CC -!- TISSUE SPECIFICITY: Expressed in heart, skeletal muscle, spleen, liver,
CC small intestine, placenta, lung and peripheral blood leukocytes
CC (PubMed:11064105). No expression is seen in brain and thymus
CC (PubMed:11064105). {ECO:0000269|PubMed:11064105}.
CC -!- INDUCTION: By IFNG/IFN-gamma. Up-regulated in TNF treated lung
CC fibroblasts. {ECO:0000269|PubMed:11064105,
CC ECO:0000269|PubMed:18546154}.
CC -!- DOMAIN: In human, and in contrast to mouse protein, the SAM domain is
CC not required for deoxynucleoside triphosphate (dNTPase) activity and
CC ability to restrict infection by viruses.
CC {ECO:0000269|PubMed:29379009}.
CC -!- PTM: Phosphorylation at Thr-592 by CDK1 acts as a switch to control
CC deoxynucleoside triphosphate (dNTPase)-dependent and -independent
CC functions (PubMed:29670289). Phosphorylation at Thr-592 takes place in
CC cycling cells: it reduces the stability of the homotetramer, impairing
CC the dNTPase activity and subsequent ability to restrict infection by
CC viruses (PubMed:23602554, PubMed:23601106, PubMed:26294762,
CC PubMed:26431200, PubMed:31291580). It also inhibits ability to suppress
CC LINE-1 retrotransposon activity (PubMed:29610582). In contrast,
CC phosphorylation at Thr-592 promotes DNA end resection at stalled
CC replication forks in response to DNA damage (PubMed:29670289).
CC {ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554,
CC ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200,
CC ECO:0000269|PubMed:29610582, ECO:0000269|PubMed:29670289}.
CC -!- PTM: (Microbial infection) Phosphorylation at Thr-592 by Epstein-Barr
CC virus kinase BGLF4 and human cytomegalovirus/HCMV UL97 leads to a
CC reduced level of dCTPase and dTTPase activity and the loss of viral
CC restriction. {ECO:0000269|PubMed:31291580,
CC ECO:0000269|PubMed:31548682}.
CC -!- PTM: (Microbial infection) Ubiquitinated following interaction with
CC HIV-2 viral protein Vpx; Vpx promotes interaction and with a DCX (DDB1-
CC CUL4-X-box) E3 ubiquitin ligase, leading to proteasomal degradation.
CC {ECO:0000269|PubMed:21613998, ECO:0000269|PubMed:21720370,
CC ECO:0000269|PubMed:22056990, ECO:0000269|PubMed:24336198}.
CC -!- DISEASE: Aicardi-Goutieres syndrome 5 (AGS5) [MIM:612952]: A form of
CC Aicardi-Goutieres syndrome, a genetically heterogeneous disease
CC characterized by cerebral atrophy, leukoencephalopathy, intracranial
CC calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis,
CC increased CSF alpha-interferon, and negative serologic investigations
CC for common prenatal infection. Clinical features as thrombocytopenia,
CC hepatosplenomegaly and elevated hepatic transaminases along with
CC intermittent fever may erroneously suggest an infective process. Severe
CC neurological dysfunctions manifest in infancy as progressive
CC microcephaly, spasticity, dystonic posturing and profound psychomotor
CC retardation. Death often occurs in early childhood.
CC {ECO:0000269|PubMed:19525956, ECO:0000269|PubMed:20131292,
CC ECO:0000269|PubMed:20842748, ECO:0000269|PubMed:24035396,
CC ECO:0000269|PubMed:24183309, ECO:0000269|PubMed:28229507,
CC ECO:0000269|PubMed:29670289}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Chilblain lupus 2 (CHBL2) [MIM:614415]: A rare cutaneous form
CC of lupus erythematosus. Affected individuals present with painful
CC bluish-red papular or nodular lesions of the skin in acral locations
CC precipitated by cold and wet exposure. {ECO:0000269|PubMed:21204240}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: Catalytically inactive. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Catalytically inactive. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the SAMHD1 family. {ECO:0000305}.
CC -!- CAUTION: Was intially thought to be allosterically stimulated by dGTP
CC (PubMed:22056990, PubMed:24141705, PubMed:24217394). However, it was
CC later shown that it is allosterically activated and regulated via the
CC combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP), which
CC bind two separate binding sites (PubMed:25288794, PubMed:25267621,
CC PubMed:25760601). {ECO:0000269|PubMed:22056990,
CC ECO:0000269|PubMed:24141705, ECO:0000269|PubMed:24217394,
CC ECO:0000269|PubMed:25267621, ECO:0000269|PubMed:25288794,
CC ECO:0000269|PubMed:25760601}.
CC -!- CAUTION: Phosphorylation at Thr-592 was initially thought to impair
CC ability to restrict infection by viruses without affecting the
CC deoxynucleoside triphosphate (dNTPase) activity (PubMed:23601106).
CC However, it was later shown that phosphorylation reduces the stability
CC of the homotetramer, leading to impair the dNTPase activity
CC (PubMed:26294762, PubMed:26431200). {ECO:0000269|PubMed:23601106,
CC ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200}.
CC -!- CAUTION: Was initially thought to have 3'-5' exonuclease activity,
CC acting on single-stranded RNA (PubMed:23364794, PubMed:25038827). A
CC publication also reported some DNA 3'-5' exonuclease activity
CC (PubMed:23364794). However, it was later shown that SAMHD1 does not
CC possess DNA and/or RNA exonuclease activities and that these activities
CC are due to contamination during the purification process that can be
CC removed after chromatography steps (PubMed:26101257). The exonuclease
CC activity observed was maybe due to the presence of MRE11 during the
CC purification steps (PubMed:29670289). {ECO:0000269|PubMed:23364794,
CC ECO:0000269|PubMed:25038827, ECO:0000269|PubMed:26101257,
CC ECO:0000269|PubMed:29670289}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAG65067.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice sites.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AF228421; AAF32407.1; -; mRNA.
DR EMBL; AB013847; BAB18916.1; -; mRNA.
DR EMBL; AL050267; CAB43368.1; -; mRNA.
DR EMBL; AK027811; BAB55386.1; -; mRNA.
DR EMBL; AK304187; BAG65067.1; ALT_SEQ; mRNA.
DR EMBL; AL079335; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL365505; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76090.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76091.1; -; Genomic_DNA.
DR EMBL; BC036450; AAH36450.1; -; mRNA.
DR CCDS; CCDS13288.1; -. [Q9Y3Z3-1]
DR CCDS; CCDS86953.1; -. [Q9Y3Z3-4]
DR PIR; T08686; T08686.
DR RefSeq; NP_056289.2; NM_015474.3. [Q9Y3Z3-1]
DR RefSeq; XP_005260441.1; XM_005260384.3.
DR PDB; 2E8O; NMR; -; A=23-118.
DR PDB; 3U1N; X-ray; 3.10 A; A/B/C/D=120-626.
DR PDB; 4BZB; X-ray; 1.83 A; A/B/C/D=113-626.
DR PDB; 4BZC; X-ray; 2.88 A; A/B/C/D=113-626.
DR PDB; 4CC9; X-ray; 2.47 A; C=582-626.
DR PDB; 4MZ7; X-ray; 1.80 A; A/B=109-626.
DR PDB; 4Q7H; X-ray; 2.59 A; A/B/C/D=109-626.
DR PDB; 4QFX; X-ray; 2.20 A; A/B/C/D=113-626.
DR PDB; 4QFY; X-ray; 2.10 A; A/B/C/D=113-626.
DR PDB; 4QFZ; X-ray; 2.30 A; A/B/C/D=113-626.
DR PDB; 4QG0; X-ray; 2.30 A; A/B/C/D=113-626.
DR PDB; 4QG1; X-ray; 2.20 A; A/B/C/D=113-626.
DR PDB; 4QG2; X-ray; 2.25 A; A/B/C/D=113-626.
DR PDB; 4QG4; X-ray; 2.10 A; A/B/C/D=113-626.
DR PDB; 4RXO; X-ray; 2.60 A; A/B/C/D=109-626.
DR PDB; 4RXP; X-ray; 2.10 A; A/B=109-626.
DR PDB; 4RXQ; X-ray; 2.10 A; A/B=109-626.
DR PDB; 4RXR; X-ray; 2.12 A; A/B=109-626.
DR PDB; 4RXS; X-ray; 2.20 A; A/B=109-626.
DR PDB; 4TNP; X-ray; 2.00 A; A/B/C/D=113-626.
DR PDB; 4TNQ; X-ray; 2.55 A; A/B/C/D=113-626.
DR PDB; 4TNR; X-ray; 2.75 A; A/B/C/D=113-626.
DR PDB; 4TNX; X-ray; 2.31 A; A/B/C/D=113-626.
DR PDB; 4TNY; X-ray; 2.60 A; A/B/C/D=113-626.
DR PDB; 4TNZ; X-ray; 2.38 A; A/B/C/D=113-626.
DR PDB; 4TO0; X-ray; 2.30 A; A/B/C/D=113-626.
DR PDB; 4TO1; X-ray; 2.55 A; A/B/C/D=113-626.
DR PDB; 4TO2; X-ray; 2.27 A; A/B/C/D=113-626.
DR PDB; 4TO3; X-ray; 2.20 A; A/B/C/D=113-626.
DR PDB; 4TO4; X-ray; 2.10 A; A/B/C/D=113-626.
DR PDB; 4TO5; X-ray; 2.80 A; A/B/C/D=113-626.
DR PDB; 4TO6; X-ray; 2.33 A; A/B/C/D=113-626.
DR PDB; 4ZWE; X-ray; 2.81 A; A/B/C/D=113-626.
DR PDB; 4ZWG; X-ray; 2.30 A; A/B/C/D=113-626.
DR PDB; 5AO0; X-ray; 3.73 A; A/B=41-583.
DR PDB; 5AO1; X-ray; 2.54 A; A/B/C/D=115-583.
DR PDB; 5AO2; X-ray; 2.97 A; A/B/C/D=115-583.
DR PDB; 5AO3; X-ray; 3.00 A; A/B/C/D=115-626.
DR PDB; 5AO4; X-ray; 3.70 A; A/B/C/D=115-626.
DR PDB; 6CM2; X-ray; 2.14 A; A/B/C/D=113-626.
DR PDB; 6DW3; X-ray; 2.20 A; A/B/C/D=113-626.
DR PDB; 6DW4; X-ray; 1.99 A; A/B/C/D=113-626.
DR PDB; 6DW5; X-ray; 1.93 A; A/B/C/D=113-626.
DR PDB; 6DW7; X-ray; 2.50 A; A/B/C/D=113-626.
DR PDB; 6DWD; X-ray; 1.70 A; A/B/C/D=113-626.
DR PDB; 6DWJ; X-ray; 2.50 A; A/B/C/D=113-626.
DR PDB; 6DWK; X-ray; 2.30 A; A/B/C/D=113-626.
DR PDB; 6TX0; X-ray; 2.01 A; A/B=109-626.
DR PDB; 6TXA; X-ray; 2.85 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=109-626.
DR PDB; 6TXC; X-ray; 2.84 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=109-626.
DR PDB; 6TXE; X-ray; 3.19 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=109-626.
DR PDB; 6TXF; X-ray; 2.25 A; A/B=109-626.
DR PDB; 6U6X; X-ray; 2.58 A; A/B/C/D=114-626.
DR PDB; 6U6Y; X-ray; 2.47 A; A/B/C/D=114-626.
DR PDB; 6U6Z; X-ray; 2.10 A; A/B/C/D=116-626.
DR PDB; 6XU1; X-ray; 2.20 A; A/B/C/D/E/F/G/H=109-626.
DR PDB; 6YOM; X-ray; 3.25 A; A/B=109-626.
DR PDB; 7A5Y; X-ray; 2.29 A; A/B/C/D/E/F/G/H=109-626.
DR PDB; 7LTT; X-ray; 1.90 A; A/B/C/D=113-626.
DR PDB; 7LU5; X-ray; 3.57 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=113-626.
DR PDB; 7S2Y; X-ray; 2.80 A; A/B/C/D=113-626.
DR PDBsum; 2E8O; -.
DR PDBsum; 3U1N; -.
DR PDBsum; 4BZB; -.
DR PDBsum; 4BZC; -.
DR PDBsum; 4CC9; -.
DR PDBsum; 4MZ7; -.
DR PDBsum; 4Q7H; -.
DR PDBsum; 4QFX; -.
DR PDBsum; 4QFY; -.
DR PDBsum; 4QFZ; -.
DR PDBsum; 4QG0; -.
DR PDBsum; 4QG1; -.
DR PDBsum; 4QG2; -.
DR PDBsum; 4QG4; -.
DR PDBsum; 4RXO; -.
DR PDBsum; 4RXP; -.
DR PDBsum; 4RXQ; -.
DR PDBsum; 4RXR; -.
DR PDBsum; 4RXS; -.
DR PDBsum; 4TNP; -.
DR PDBsum; 4TNQ; -.
DR PDBsum; 4TNR; -.
DR PDBsum; 4TNX; -.
DR PDBsum; 4TNY; -.
DR PDBsum; 4TNZ; -.
DR PDBsum; 4TO0; -.
DR PDBsum; 4TO1; -.
DR PDBsum; 4TO2; -.
DR PDBsum; 4TO3; -.
DR PDBsum; 4TO4; -.
DR PDBsum; 4TO5; -.
DR PDBsum; 4TO6; -.
DR PDBsum; 4ZWE; -.
DR PDBsum; 4ZWG; -.
DR PDBsum; 5AO0; -.
DR PDBsum; 5AO1; -.
DR PDBsum; 5AO2; -.
DR PDBsum; 5AO3; -.
DR PDBsum; 5AO4; -.
DR PDBsum; 6CM2; -.
DR PDBsum; 6DW3; -.
DR PDBsum; 6DW4; -.
DR PDBsum; 6DW5; -.
DR PDBsum; 6DW7; -.
DR PDBsum; 6DWD; -.
DR PDBsum; 6DWJ; -.
DR PDBsum; 6DWK; -.
DR PDBsum; 6TX0; -.
DR PDBsum; 6TXA; -.
DR PDBsum; 6TXC; -.
DR PDBsum; 6TXE; -.
DR PDBsum; 6TXF; -.
DR PDBsum; 6U6X; -.
DR PDBsum; 6U6Y; -.
DR PDBsum; 6U6Z; -.
DR PDBsum; 6XU1; -.
DR PDBsum; 6YOM; -.
DR PDBsum; 7A5Y; -.
DR PDBsum; 7LTT; -.
DR PDBsum; 7LU5; -.
DR PDBsum; 7S2Y; -.
DR AlphaFoldDB; Q9Y3Z3; -.
DR SMR; Q9Y3Z3; -.
DR BioGRID; 117436; 170.
DR DIP; DIP-50704N; -.
DR IntAct; Q9Y3Z3; 55.
DR MINT; Q9Y3Z3; -.
DR STRING; 9606.ENSP00000262878; -.
DR ChEMBL; CHEMBL4523507; -.
DR CarbonylDB; Q9Y3Z3; -.
DR GlyGen; Q9Y3Z3; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q9Y3Z3; -.
DR PhosphoSitePlus; Q9Y3Z3; -.
DR BioMuta; SAMHD1; -.
DR DMDM; 22257047; -.
DR CPTAC; CPTAC-945; -.
DR EPD; Q9Y3Z3; -.
DR jPOST; Q9Y3Z3; -.
DR MassIVE; Q9Y3Z3; -.
DR MaxQB; Q9Y3Z3; -.
DR PaxDb; Q9Y3Z3; -.
DR PeptideAtlas; Q9Y3Z3; -.
DR PRIDE; Q9Y3Z3; -.
DR ProteomicsDB; 86088; -. [Q9Y3Z3-1]
DR Antibodypedia; 26616; 487 antibodies from 36 providers.
DR DNASU; 25939; -.
DR Ensembl; ENST00000262878.5; ENSP00000262878.5; ENSG00000101347.11. [Q9Y3Z3-4]
DR Ensembl; ENST00000644250.2; ENSP00000493810.2; ENSG00000101347.11. [Q9Y3Z3-4]
DR Ensembl; ENST00000646066.1; ENSP00000495432.1; ENSG00000101347.11. [Q9Y3Z3-3]
DR Ensembl; ENST00000646673.2; ENSP00000493536.2; ENSG00000101347.11. [Q9Y3Z3-1]
DR Ensembl; ENST00000646869.1; ENSP00000495667.1; ENSG00000101347.11. [Q9Y3Z3-1]
DR Ensembl; ENST00000682773.1; ENSP00000507178.1; ENSG00000101347.11. [Q9Y3Z3-1]
DR Ensembl; ENST00000683766.1; ENSP00000506877.1; ENSG00000101347.11. [Q9Y3Z3-1]
DR GeneID; 25939; -.
DR KEGG; hsa:25939; -.
DR MANE-Select; ENST00000646673.2; ENSP00000493536.2; NM_015474.4; NP_056289.2.
DR UCSC; uc002xgh.3; human. [Q9Y3Z3-1]
DR CTD; 25939; -.
DR DisGeNET; 25939; -.
DR GeneCards; SAMHD1; -.
DR GeneReviews; SAMHD1; -.
DR HGNC; HGNC:15925; SAMHD1.
DR HPA; ENSG00000101347; Low tissue specificity.
DR MalaCards; SAMHD1; -.
DR MIM; 606754; gene.
DR MIM; 612952; phenotype.
DR MIM; 614415; phenotype.
DR neXtProt; NX_Q9Y3Z3; -.
DR OpenTargets; ENSG00000101347; -.
DR Orphanet; 51; Aicardi-Goutieres syndrome.
DR Orphanet; 481662; Familial Chilblain lupus.
DR PharmGKB; PA34938; -.
DR VEuPathDB; HostDB:ENSG00000101347; -.
DR eggNOG; KOG2681; Eukaryota.
DR GeneTree; ENSGT00390000013867; -.
DR HOGENOM; CLU_026821_1_2_1; -.
DR InParanoid; Q9Y3Z3; -.
DR OMA; GPEQVCF; -.
DR PhylomeDB; Q9Y3Z3; -.
DR TreeFam; TF316113; -.
DR BRENDA; 3.1.5.B1; 2681.
DR PathwayCommons; Q9Y3Z3; -.
DR Reactome; R-HSA-8956319; Nucleotide catabolism.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR SignaLink; Q9Y3Z3; -.
DR SIGNOR; Q9Y3Z3; -.
DR BioGRID-ORCS; 25939; 28 hits in 1081 CRISPR screens.
DR ChiTaRS; SAMHD1; human.
DR EvolutionaryTrace; Q9Y3Z3; -.
DR GeneWiki; SAMHD1; -.
DR GenomeRNAi; 25939; -.
DR Pharos; Q9Y3Z3; Tbio.
DR PRO; PR:Q9Y3Z3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9Y3Z3; protein.
DR Bgee; ENSG00000101347; Expressed in monocyte and 205 other tissues.
DR ExpressionAtlas; Q9Y3Z3; baseline and differential.
DR Genevisible; Q9Y3Z3; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0097197; C:tetraspanin-enriched microdomain; IDA:UniProtKB.
DR GO; GO:0106375; F:deoxynucleoside triphosphate hydrolase activity; IEA:RHEA.
DR GO; GO:0032567; F:dGTP binding; IDA: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; IPI:IntAct.
DR GO; GO:0003676; F:nucleic acid binding; IDA:UniProtKB.
DR GO; GO:0004540; F:ribonuclease activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0016793; F:triphosphoric monoester hydrolase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0046061; P:dATP catabolic process; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0009264; P:deoxyribonucleotide catabolic process; IDA:UniProtKB.
DR GO; GO:0006203; P:dGTP catabolic process; IDA:UniProtKB.
DR GO; GO:0110025; P:DNA strand resection involved in replication fork processing; IDA:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:0006955; P:immune response; NAS: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; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; IDA:UniProtKB.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; ISS: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; Acetylation; Aicardi-Goutieres syndrome; Allosteric enzyme;
KW Alternative splicing; Antiviral defense; Chromosome;
KW Direct protein sequencing; Disease variant; DNA damage; DNA repair;
KW DNA replication; GTP-binding; Host-virus interaction; Hydrolase; Immunity;
KW Innate immunity; Isopeptide bond; Metal-binding; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation; Zinc.
FT CHAIN 1..626
FT /note="Deoxynucleoside triphosphate triphosphohydrolase
FT SAMHD1"
FT /id="PRO_0000153732"
FT DOMAIN 45..110
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT DOMAIN 164..316
FT /note="HD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 233
FT /evidence="ECO:0000305|PubMed:22056990"
FT BINDING 116
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:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
FT ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200"
FT BINDING 119
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:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
FT ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200"
FT BINDING 137..145
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:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
FT ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200"
FT BINDING 149
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24141705"
FT BINDING 164
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24141705"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25288794,
FT ECO:0000269|PubMed:25760601, ECO:0000269|PubMed:26431200"
FT BINDING 206
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25288794,
FT ECO:0000269|PubMed:25760601, ECO:0000269|PubMed:26431200"
FT BINDING 207
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25288794,
FT ECO:0000269|PubMed:25760601, ECO:0000269|PubMed:26431200"
FT BINDING 210
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24141705"
FT BINDING 309..315
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24141705"
FT BINDING 311
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25288794,
FT ECO:0000269|PubMed:25760601, ECO:0000269|PubMed:26431200"
FT BINDING 315
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24141705"
FT BINDING 319
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24141705"
FT BINDING 333
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:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
FT ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200"
FT BINDING 352..354
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:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
FT ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200"
FT BINDING 358
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:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
FT ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200"
FT BINDING 366
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24141705"
FT BINDING 370..375
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24141705"
FT BINDING 376
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:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
FT ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200"
FT BINDING 377
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:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
FT ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200"
FT BINDING 451
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
FT ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200"
FT BINDING 455
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
FT ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200"
FT BINDING 523
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:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621,
FT ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19413330"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60710"
FT MOD_RES 21
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60710"
FT MOD_RES 25
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60710"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 93
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 592
FT /note="(Microbial infection) Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:31291580,
FT ECO:0000269|PubMed:31548682"
FT MOD_RES 592
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000269|PubMed:23601106,
FT ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:26294762,
FT ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:29610582,
FT ECO:0000269|PubMed:29670289, ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT CROSSLNK 467
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 469
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 492
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 622
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 285..354
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046561"
FT VAR_SEQ 502..536
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_046562"
FT VARIANT 120..123
FT /note="Missing (in AGS5)"
FT /evidence="ECO:0000269|PubMed:24183309"
FT /id="VAR_078239"
FT VARIANT 123
FT /note="H -> P (in AGS5; loss of oligomerization; decreased
FT ability to restrict LINE-1 retrotransposon activity;
FT dbSNP:rs121434520)"
FT /evidence="ECO:0000269|PubMed:19525956,
FT ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:24183309,
FT ECO:0000269|PubMed:28229507"
FT /id="VAR_058481"
FT VARIANT 143
FT /note="R -> C (in AGS5; loss of oligomerization;
FT dbSNP:rs387906948)"
FT /evidence="ECO:0000269|PubMed:19525956,
FT ECO:0000269|PubMed:28229507"
FT /id="VAR_058482"
FT VARIANT 143
FT /note="R -> H (in AGS5; loss of oligomerization; decreased
FT ability to restrict LINE-1 retrotransposon activity;
FT dbSNP:rs369035155)"
FT /evidence="ECO:0000269|PubMed:19525956,
FT ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:24183309,
FT ECO:0000269|PubMed:28229507"
FT /id="VAR_058483"
FT VARIANT 145
FT /note="R -> Q (in AGS5; loss of oligomerization; decreased
FT ability to restrict LINE-1 retrotransposon activity;
FT dbSNP:rs515726145)"
FT /evidence="ECO:0000269|PubMed:19525956,
FT ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:28229507"
FT /id="VAR_058484"
FT VARIANT 167
FT /note="H -> Y (in AGS5; loss of function in defense
FT response to virus; loss of oligomerization; decreased
FT ability to restrict LINE-1 retrotransposon activity)"
FT /evidence="ECO:0000269|PubMed:20131292,
FT ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:28229507"
FT /id="VAR_070633"
FT VARIANT 201
FT /note="I -> N (in AGS5 and CHBL2; loss of function in
FT defense response to virus; decreased oligomerization;
FT decreased ability to restrict LINE-1 retrotransposon
FT activity; dbSNP:rs138603088)"
FT /evidence="ECO:0000269|PubMed:19525956,
FT ECO:0000269|PubMed:21204240, ECO:0000269|PubMed:24035396,
FT ECO:0000269|PubMed:24183309, ECO:0000269|PubMed:28229507"
FT /id="VAR_058485"
FT VARIANT 209
FT /note="G -> S (in AGS5; does not affect oligomerization;
FT decreased ability to restrict LINE-1 retrotransposon
FT activity; does not affect localization to nucleus;
FT dbSNP:rs121434516)"
FT /evidence="ECO:0000269|PubMed:19525956,
FT ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:28229507"
FT /id="VAR_058486"
FT VARIANT 254
FT /note="M -> V (in AGS5; loss of function in defense
FT response to virus; does not affect oligomerization;
FT decreased ability to restrict LINE-1 retrotransposon
FT activity; dbSNP:rs121434521)"
FT /evidence="ECO:0000269|PubMed:19525956,
FT ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:24183309,
FT ECO:0000269|PubMed:28229507"
FT /id="VAR_058487"
FT VARIANT 290
FT /note="R -> H (in AGS5; loss of oligomerization; decreased
FT ability to restrict LINE-1 retrotransposon activity;
FT dbSNP:rs559553527)"
FT /evidence="ECO:0000269|PubMed:20131292,
FT ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:28229507"
FT /id="VAR_070634"
FT VARIANT 369
FT /note="L -> S (in AGS5; loss of function in defense
FT response to virus; decreased oligomerization;
FT dbSNP:rs515726139)"
FT /evidence="ECO:0000269|PubMed:19525956,
FT ECO:0000269|PubMed:28229507"
FT /id="VAR_058488"
FT VARIANT 385
FT /note="M -> V (in AGS5; loss of function in defense
FT response to virus; loss of oligomerization;
FT dbSNP:rs515726140)"
FT /evidence="ECO:0000269|PubMed:19525956,
FT ECO:0000269|PubMed:24183309, ECO:0000269|PubMed:28229507"
FT /id="VAR_058489"
FT VARIANT 448
FT /note="I -> T (in AGS5; loss of function in defense
FT response to virus; decreased oligomerization; does not
FT affect localization to nucleus; novel localization to the
FT cytoplasm; dbSNP:rs774964432)"
FT /evidence="ECO:0000269|PubMed:24183309,
FT ECO:0000269|PubMed:28229507"
FT /id="VAR_078240"
FT VARIANT 548..626
FT /note="Missing (in AGS5; Does not affect dNTP regulation,
FT while affecting ability to promote DNA end resection at
FT stalled replication forks)"
FT /evidence="ECO:0000269|PubMed:29670289"
FT /id="VAR_080530"
FT MUTAGEN 77
FT /note="L->F: Increased stability of the tetramer and
FT increased deoxynucleoside triphosphate (dNTPase) activity;
FT when associated with F-77 and F-80 and R-111."
FT /evidence="ECO:0000269|PubMed:29379009"
FT MUTAGEN 80
FT /note="C->F: Increased stability of the tetramer and
FT increased deoxynucleoside triphosphate (dNTPase) activity;
FT when associated with F-77 and R-111."
FT /evidence="ECO:0000269|PubMed:29379009"
FT MUTAGEN 111
FT /note="H->R: Increased stability of the tetramer and
FT increased deoxynucleoside triphosphate (dNTPase) activity;
FT when associated with F-77 and F-80."
FT /evidence="ECO:0000269|PubMed:29379009"
FT MUTAGEN 137
FT /note="D->A: Impairs homotetramerization and nearly
FT abolishes dNTPase activity."
FT /evidence="ECO:0000269|PubMed:24217394,
FT ECO:0000269|PubMed:25038827, ECO:0000269|PubMed:25288794"
FT MUTAGEN 142
FT /note="Q->E,A: Impairs homotetramerization and nearly
FT abolishes dNTPase activity; when associated with K-145."
FT /evidence="ECO:0000269|PubMed:24217394,
FT ECO:0000269|PubMed:25288794"
FT MUTAGEN 143
FT /note="R->A: Abolished ability to restrict infection by
FT viruses."
FT /evidence="ECO:0000269|PubMed:26431200"
FT MUTAGEN 145
FT /note="R->A: Impairs homotetramerization and nearly
FT abolishes dNTPase activity. Abolished ability to restrict
FT infection by viruses."
FT /evidence="ECO:0000269|PubMed:25288794,
FT ECO:0000269|PubMed:26431200"
FT MUTAGEN 145
FT /note="R->K: Impairs homotetramerization and nearly
FT abolishes dNTPase activity; when associated with E-145."
FT /evidence="ECO:0000269|PubMed:24217394"
FT MUTAGEN 149
FT /note="Q->A: Abolished dNTPase activity without affecting
FT homotetramerization. Abolished dNTPase activity; when
FT associated with A-319."
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:25288794"
FT MUTAGEN 164
FT /note="R->A: Abolished ability to restrict infection by
FT viruses."
FT /evidence="ECO:0000269|PubMed:26431200"
FT MUTAGEN 167
FT /note="H->A: Abolished ability to restrict infection by
FT viruses."
FT /evidence="ECO:0000269|PubMed:26431200"
FT MUTAGEN 206..207
FT /note="HD->RN: Abolishes zinc binding and dNTPase activity.
FT Does not affect ability to promote DNA end resection at
FT stalled replication forks."
FT /evidence="ECO:0000269|PubMed:21613998,
FT ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:26101257, ECO:0000269|PubMed:28834754"
FT MUTAGEN 206
FT /note="H->A: Abolished ability to restrict infection by
FT viruses."
FT /evidence="ECO:0000269|PubMed:26431200"
FT MUTAGEN 207
FT /note="D->A: Abolished ability to restrict infection by
FT viruses."
FT /evidence="ECO:0000269|PubMed:26431200"
FT MUTAGEN 207
FT /note="D->N,A: Loss of dNTPase activity."
FT /evidence="ECO:0000269|PubMed:25038827,
FT ECO:0000269|PubMed:26101257"
FT MUTAGEN 210
FT /note="H->A: Abolished dNTPase activity without affecting
FT homotetramerization."
FT /evidence="ECO:0000269|PubMed:25288794"
FT MUTAGEN 215
FT /note="H->A: Abolished dNTPase activity without affecting
FT homotetramerization."
FT /evidence="ECO:0000269|PubMed:25288794"
FT MUTAGEN 226
FT /note="R->G: Loss of function in defense response to
FT virus."
FT /evidence="ECO:0000269|PubMed:28229507"
FT MUTAGEN 233
FT /note="H->A: Abolished dNTPase activity without affecting
FT homotetramerization. Abolished ability to restrict
FT infection by viruses."
FT /evidence="ECO:0000269|PubMed:25288794,
FT ECO:0000269|PubMed:26431200"
FT MUTAGEN 311
FT /note="D->A: Loss of function in defense response to virus.
FT Loss of dNTPase activity. Does not affect oligomerization."
FT /evidence="ECO:0000269|PubMed:25038827,
FT ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:28229507"
FT MUTAGEN 312
FT /note="K->A: Abolishes dNTPase activity; when associated
FT with A-315 and A-366. Does not affect ability to promote
FT DNA end resection at stalled replication forks; when
FT associated with A-315."
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:29670289"
FT MUTAGEN 315
FT /note="Y->A: Abolished ability to restrict infection by
FT viruses. Abolishes dNTPase activity; when associated with
FT A-312 and A-366. Does not affect ability to promote DNA end
FT resection at stalled replication forks; when associated
FT with A-312."
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:29670289"
FT MUTAGEN 319
FT /note="D->A: Abolishes dNTPase activity; when associated
FT with A-149."
FT /evidence="ECO:0000269|PubMed:24141705"
FT MUTAGEN 321
FT /note="H->A: Abolished ability to restrict infection by
FT viruses."
FT /evidence="ECO:0000269|PubMed:26431200"
FT MUTAGEN 330
FT /note="D->A: Impaired homotetramerization and slightly
FT reduced dNTPase activity. Impaired homotetramerization and
FT reduced dNTPase activity; when associated with A-358."
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:25288794"
FT MUTAGEN 333
FT /note="R->E: Decreases dNTPase activity. Impairs
FT homotetramerization and nearly abolishes dNTPase activity;
FT when associated with E-451."
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:24217394"
FT MUTAGEN 352
FT /note="R->A: Impairs homotetramerization and abolishes
FT dNTPase activity; when associated with A-376 and A-377."
FT /evidence="ECO:0000269|PubMed:24141705"
FT MUTAGEN 358
FT /note="N->A: Impaired homotetramerization and slightly
FT reduced dNTPase activity. Impaired homotetramerization and
FT reduced dNTPase activity A-330."
FT /evidence="ECO:0000269|PubMed:24141705,
FT ECO:0000269|PubMed:25288794"
FT MUTAGEN 361
FT /note="D->R: Impairs homotetramerization and nearly
FT abolishes dNTPase activity; when associated with K-364."
FT /evidence="ECO:0000269|PubMed:24141705"
FT MUTAGEN 364
FT /note="H->K: Impairs homotetramerization and nearly
FT abolishes dNTPase activity; when associated with R-361."
FT /evidence="ECO:0000269|PubMed:24141705"
FT MUTAGEN 366
FT /note="R->A: Abolishes dNTPase activity; when associated
FT with A-312 and A-315."
FT /evidence="ECO:0000269|PubMed:24141705"
FT MUTAGEN 370
FT /note="H->A: Abolishes dNTPase activity; when associated
FT with G-374."
FT /evidence="ECO:0000269|PubMed:24141705"
FT MUTAGEN 372
FT /note="R->D: Abolished homotetramerization and dNTPase
FT activity."
FT /evidence="ECO:0000269|PubMed:26431200"
FT MUTAGEN 374
FT /note="Y->G: Abolishes dNTPase activity; when associated
FT with A-370."
FT /evidence="ECO:0000269|PubMed:24141705"
FT MUTAGEN 375
FT /note="Q->A: Abolished dNTPase activity without affecting
FT homotetramerization."
FT /evidence="ECO:0000269|PubMed:25288794"
FT MUTAGEN 376
FT /note="H->A: Impairs homotetramerization and abolishes
FT dNTPase activity; when associated with A-352 and A-377."
FT MUTAGEN 377
FT /note="K->A: Impairs homotetramerization and abolishes
FT dNTPase activity; when associated with A-352 and A-376."
FT MUTAGEN 451
FT /note="R->E: Impairs homotetramerization and abolishes
FT dNTPase activity."
FT /evidence="ECO:0000269|PubMed:24217394,
FT ECO:0000269|PubMed:26101257"
FT MUTAGEN 534
FT /note="K->A: Impairs homotetramerization and abolishes
FT dNTPase activity; when associated with A-537 and D-540."
FT /evidence="ECO:0000269|PubMed:24141705"
FT MUTAGEN 537
FT /note="V->A: Impairs homotetramerization and abolishes
FT dNTPase activity; when associated with A-534 and D-540."
FT /evidence="ECO:0000269|PubMed:24141705"
FT MUTAGEN 540
FT /note="L->D: Impairs homotetramerization and abolishes
FT dNTPase activity; when associated with A-537 and A-534."
FT /evidence="ECO:0000269|PubMed:24141705"
FT MUTAGEN 548
FT /note="Q->A: Loss of function in defense response to virus.
FT Does not affect oligomerization. Retains dNTPase activity."
FT /evidence="ECO:0000269|PubMed:26101257,
FT ECO:0000269|PubMed:28229507"
FT MUTAGEN 592
FT /note="T->A,V: Impaired ability to promote DNA end
FT resection at stalled replication forks. Promotes dNTPase
FT activity and ability to restrict infection by viruses."
FT /evidence="ECO:0000269|PubMed:23601106,
FT ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:26294762,
FT ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:29610582,
FT ECO:0000269|PubMed:29670289"
FT MUTAGEN 592
FT /note="T->A: Loss of phosphorylation by human
FT cytomegalovirus/HCMV kinase UL97."
FT /evidence="ECO:0000269|PubMed:31548682"
FT MUTAGEN 592
FT /note="T->E: Mimicks phosphorylation state, retains ability
FT to promote DNA end resection at stalled replication forks.
FT Induces large conformational changes that impair
FT homotetramerization, leading to reduced dNTPase activity
FT and decreased ability to restrict infection by viruses."
FT /evidence="ECO:0000269|PubMed:23601106,
FT ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:26101257,
FT ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200,
FT ECO:0000269|PubMed:29610582, ECO:0000269|PubMed:29670289"
FT MUTAGEN 593
FT /note="P->A: Promotes ability to restrict infection by
FT viruses."
FT /evidence="ECO:0000269|PubMed:23601106"
FT MUTAGEN 609
FT /note="R->A,E: Abolishes proteasomal degradation triggered
FT by the viral accessory protein vpx."
FT /evidence="ECO:0000269|PubMed:24336198"
FT MUTAGEN 617
FT /note="R->A,E: Abolishes proteasomal degradation triggered
FT by the viral accessory protein vpx."
FT /evidence="ECO:0000269|PubMed:24336198"
FT MUTAGEN 622
FT /note="K->A,E: Abolishes proteasomal degradation triggered
FT by the viral accessory protein vpx."
FT /evidence="ECO:0000269|PubMed:24336198"
FT CONFLICT 394
FT /note="D -> G (in Ref. 1; AAF32407 and 3; CAB43368)"
FT /evidence="ECO:0000305"
FT CONFLICT 404
FT /note="G -> E (in Ref. 7; AAH36450)"
FT /evidence="ECO:0000305"
FT CONFLICT 494
FT /note="K -> E (in Ref. 1; AAF32407 and 3; CAB43368)"
FT /evidence="ECO:0000305"
FT CONFLICT 546
FT /note="A -> V (in Ref. 7; AAH36450)"
FT /evidence="ECO:0000305"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:2E8O"
FT HELIX 46..57
FT /evidence="ECO:0007829|PDB:2E8O"
FT HELIX 62..70
FT /evidence="ECO:0007829|PDB:2E8O"
FT TURN 75..80
FT /evidence="ECO:0007829|PDB:2E8O"
FT HELIX 83..88
FT /evidence="ECO:0007829|PDB:2E8O"
FT HELIX 94..108
FT /evidence="ECO:0007829|PDB:2E8O"
FT TURN 109..112
FT /evidence="ECO:0007829|PDB:2E8O"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:6DWD"
FT TURN 121..123
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 130..136
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 139..142
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 143..146
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:4QFY"
FT HELIX 151..155
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 164..185
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 193..205
FT /evidence="ECO:0007829|PDB:6DWD"
FT TURN 206..209
FT /evidence="ECO:0007829|PDB:6DWD"
FT TURN 212..214
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 215..219
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 221..225
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:6CM2"
FT HELIX 233..247
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 250..256
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 261..273
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 292..299
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:6DWD"
FT TURN 304..306
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 310..323
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 331..336
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 338..343
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 346..352
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 356..372
FT /evidence="ECO:0007829|PDB:6DWD"
FT TURN 373..375
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 377..393
FT /evidence="ECO:0007829|PDB:6DWD"
FT TURN 394..396
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 402..404
FT /evidence="ECO:0007829|PDB:6DWD"
FT TURN 409..411
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 416..419
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 425..432
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 436..438
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 439..450
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 455..460
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 464..466
FT /evidence="ECO:0007829|PDB:7A5Y"
FT HELIX 470..475
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 476..482
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 495..497
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 498..509
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 514..517
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 520..522
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 525..530
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 534..536
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 541..543
FT /evidence="ECO:0007829|PDB:6DWD"
FT STRAND 545..555
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 559..576
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 584..587
FT /evidence="ECO:0007829|PDB:6DWD"
FT TURN 589..591
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 592..594
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 596..598
FT /evidence="ECO:0007829|PDB:6DWD"
FT HELIX 611..613
FT /evidence="ECO:0007829|PDB:4CC9"
FT HELIX 617..622
FT /evidence="ECO:0007829|PDB:4CC9"
SQ SEQUENCE 626 AA; 72201 MW; 559CB6BB029E6558 CRC64;
MQRADSEQPS KRPRCDDSPR TPSNTPSAEA DWSPGLELHP DYKTWGPEQV CSFLRRGGFE
EPVLLKNIRE NEITGALLPC LDESRFENLG VSSLGERKKL LSYIQRLVQI HVDTMKVIND
PIHGHIELHP LLVRIIDTPQ FQRLRYIKQL GGGYYVFPGA SHNRFEHSLG VGYLAGCLVH
ALGEKQPELQ ISERDVLCVQ IAGLCHDLGH GPFSHMFDGR FIPLARPEVK WTHEQGSVMM
FEHLINSNGI KPVMEQYGLI PEEDICFIKE QIVGPLESPV EDSLWPYKGR PENKSFLYEI
VSNKRNGIDV DKWDYFARDC HHLGIQNNFD YKRFIKFARV CEVDNELRIC ARDKEVGNLY
DMFHTRNSLH RRAYQHKVGN IIDTMITDAF LKADDYIEIT GAGGKKYRIS TAIDDMEAYT
KLTDNIFLEI LYSTDPKLKD AREILKQIEY RNLFKYVGET QPTGQIKIKR EDYESLPKEV
ASAKPKVLLD VKLKAEDFIV DVINMDYGMQ EKNPIDHVSF YCKTAPNRAI RITKNQVSQL
LPEKFAEQLI RVYCKKVDRK SLYAARQYFV QWCADRNFTK PQDGDVIAPL ITPQKKEWND
STSVQNPTRL REASKSRVQL FKDDPM
