ID DCTP1_MOUSE Reviewed; 170 AA. AC Q9QY93; DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 16-SEP-2015, entry version 100. DE RecName: Full=dCTP pyrophosphatase 1; DE EC=3.6.1.12; DE AltName: Full=Deoxycytidine-triphosphatase 1; DE Short=dCTPase 1; DE AltName: Full=RS21-C6; DE AltName: Full=XTP3-transactivated gene A protein homolog; GN Name=Dctpp1; Synonyms=Tdrg-TL1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=BALB/c; RA Wang H., Chen W.F., Li Y., Jin C.G., Wang Y., Yu Q., Qian X.P.; RT "RS21-C6: a novel gene encoding a molecule relavent to TCR and CD3 RT expression of pre-T cells."; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; 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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Mammary tumor; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION BY MASS SPECTROMETRY, RP SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE RP SPECIFICITY. RX PubMed=19220460; DOI=10.1111/j.1742-4658.2009.06898.x; RA Nonaka M., Tsuchimoto D., Sakumi K., Nakabeppu Y.; RT "Mouse RS21-C6 is a mammalian 2'-deoxycytidine 5'-triphosphate RT pyrophosphohydrolase that prefers 5-iodocytosine."; RL FEBS J. 276:1654-1666(2009). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and RT expression."; RL Cell 143:1174-1189(2010). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.32 ANGSTROMS), AND SUBUNIT. RG Center for eukaryotic structural genomics (CESG); RT "X-ray structure of protein from Mus musculus mm.29898."; RL Submitted (JUL-2005) to the PDB data bank. RN [7] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 20-126 IN COMPLEX WITH RP 5-METHYL DCTP, SUBUNIT, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF HIS-38; TRP-47; RP GLU-63; GLU-66; TRP-73; GLU-95; ASP-98 AND TYR-102. RX PubMed=17320107; DOI=10.1016/j.jmb.2007.01.057; RA Wu B., Liu Y., Zhao Q., Liao S., Zhang J., Bartlam M., Chen W., RA Rao Z.; RT "Crystal structure of RS21-C6, involved in nucleoside triphosphate RT pyrophosphohydrolysis."; RL J. Mol. Biol. 367:1405-1412(2007). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.32 ANGSTROMS). RX PubMed=17850744; DOI=10.1016/j.str.2007.06.019; RA Levin E.J., Kondrashov D.A., Wesenberg G.E., Phillips G.N. Jr.; RT "Ensemble refinement of protein crystal structures: validation and RT application."; RL Structure 15:1040-1052(2007). CC -!- FUNCTION: Hydrolyzes deoxynucleoside triphosphates (dNTPs) to the CC corresponding nucleoside monophosphates. Has a strong preference CC for modified dCTP. Activity is highest with 5-iodo-dCTP, followed CC by 5-bromo-dCTP, unmodified dCTP, 5-methyl-dCTP and 5-chloro-dCTP. CC Hydrolyzes 2-chloro-dATP and 2-hydroxy-dATP with lower efficiency, CC and has even lower activity with unmodified dATP, dTTP and dUTP CC (in vitro). Does not hydrolyze ATP, UTP, ITP, GTP, dADP, dCDP or CC dGTP. May protect DNA or RNA against the incorporation of non- CC canonical nucleotide triphosphates. May protect cells against CC inappropriate methylation of CpG islands by DNA CC methyltransferases. {ECO:0000269|PubMed:17320107, CC ECO:0000269|PubMed:19220460}. CC -!- CATALYTIC ACTIVITY: dCTP + H(2)O = dCMP + diphosphate. CC {ECO:0000269|PubMed:17320107, ECO:0000269|PubMed:19220460}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:17320107}; CC Note=Probably binds two or three Mg(2+) ions per subunit. CC {ECO:0000269|PubMed:17320107}; CC -!- ENZYME REGULATION: Inhibited by divalent calcium or cadmium ions. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.16 mM for 5-methyl-dCTP (at pH 9.0) CC {ECO:0000269|PubMed:17320107, ECO:0000269|PubMed:19220460}; CC KM=44 uM for dCTP (at pH 8.0) {ECO:0000269|PubMed:17320107, CC ECO:0000269|PubMed:19220460}; CC KM=118 uM for dATP (at pH 8.0) {ECO:0000269|PubMed:17320107, CC ECO:0000269|PubMed:19220460}; CC KM=407 uM for dTTP (at pH 8.0) {ECO:0000269|PubMed:17320107, CC ECO:0000269|PubMed:19220460}; CC KM=529 uM for CTP (at pH 8.0) {ECO:0000269|PubMed:17320107, CC ECO:0000269|PubMed:19220460}; CC KM=3.9 uM for 5-iodo-dCTP (at pH 8.0) CC {ECO:0000269|PubMed:17320107, ECO:0000269|PubMed:19220460}; CC KM=21.7 uM for 5-bromo-dCTP (at pH 8.0) CC {ECO:0000269|PubMed:17320107, ECO:0000269|PubMed:19220460}; CC KM=48.5 uM for 5-methyl-dCTP (at pH 8.0) CC {ECO:0000269|PubMed:17320107, ECO:0000269|PubMed:19220460}; CC KM=50 uM for 5-chloro-dCTP (at pH 8.0) CC {ECO:0000269|PubMed:17320107, ECO:0000269|PubMed:19220460}; CC pH dependence: CC Optimum pH is 9-9.5. {ECO:0000269|PubMed:17320107, CC ECO:0000269|PubMed:19220460}; CC Temperature dependence: CC Optimum temperature is 60 degrees Celsius. CC {ECO:0000269|PubMed:17320107, ECO:0000269|PubMed:19220460}; CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:17320107, CC ECO:0000269|Ref.6}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19220460}. CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in heart, liver, CC skeletal muscle, cerebellum, brain, and salivary gland. CC {ECO:0000269|PubMed:19220460}. CC -!- SIMILARITY: Contains 1 EAR repeat. {ECO:0000255|PROSITE- CC ProRule:PRU00075}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF110764; AAF15970.1; -; mRNA. DR EMBL; AK003643; BAB22909.1; -; mRNA. DR EMBL; AK010508; BAB26992.1; -; mRNA. DR EMBL; AK010606; BAB27056.1; -; mRNA. DR EMBL; BC004623; AAH04623.1; -; mRNA. DR CCDS; CCDS21862.1; -. DR RefSeq; NP_075692.1; NM_023203.1. DR UniGene; Mm.29898; -. DR PDB; 2A3Q; X-ray; 2.32 A; A/B=1-170. DR PDB; 2OIE; X-ray; 2.20 A; A/B/C/D=21-126. DR PDB; 2OIG; X-ray; 3.30 A; A/B/C/D=21-126. DR PDB; 2Q4P; X-ray; 2.32 A; A/B=1-170. DR PDBsum; 2A3Q; -. DR PDBsum; 2OIE; -. DR PDBsum; 2OIG; -. DR PDBsum; 2Q4P; -. DR ProteinModelPortal; Q9QY93; -. DR SMR; Q9QY93; 21-122. DR STRING; 10090.ENSMUSP00000047845; -. DR PhosphoSite; Q9QY93; -. DR MaxQB; Q9QY93; -. DR PaxDb; Q9QY93; -. DR PRIDE; Q9QY93; -. DR DNASU; 66422; -. DR Ensembl; ENSMUST00000035276; ENSMUSP00000047845; ENSMUSG00000042462. DR GeneID; 66422; -. DR KEGG; mmu:66422; -. DR UCSC; uc009juw.2; mouse. DR CTD; 79077; -. DR MGI; MGI:1913672; Dctpp1. DR eggNOG; NOG131091; -. DR GeneTree; ENSGT00390000017709; -. DR HOGENOM; HOG000056700; -. DR InParanoid; Q9QY93; -. DR KO; K16904; -. DR OMA; EQFHQPR; -. DR OrthoDB; EOG70S774; -. DR PhylomeDB; Q9QY93; -. DR TreeFam; TF300237; -. DR BioCyc; MetaCyc:MONOMER-17900; -. DR BRENDA; 3.6.1.12; 3474. DR EvolutionaryTrace; Q9QY93; -. DR NextBio; 321647; -. DR PRO; PR:Q9QY93; -. DR Proteomes; UP000000589; Chromosome 7. DR Bgee; Q9QY93; -. DR CleanEx; MM_2410015N17RIK; -. DR Genevisible; Q9QY93; MM. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0047840; F:dCTP diphosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0047429; F:nucleoside-triphosphate diphosphatase activity; IDA:UniProtKB. DR GO; GO:0032556; F:pyrimidine deoxyribonucleotide binding; IDA:MGI. DR GO; GO:0016462; F:pyrophosphatase activity; IDA:MGI. DR GO; GO:0009143; P:nucleoside triphosphate catabolic process; IDA:UniProtKB. DR GO; GO:0051289; P:protein homotetramerization; IDA:MGI. DR InterPro; IPR009039; EAR. DR InterPro; IPR004518; MazG_cat. DR Pfam; PF03819; MazG; 1. DR PROSITE; PS50912; EAR; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Complete proteome; Cytoplasm; Hydrolase; KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Reference proteome. FT INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:Q9H773}. FT CHAIN 2 170 dCTP pyrophosphatase 1. FT /FTId=PRO_0000291770. FT REPEAT 29 75 EAR. FT REGION 47 51 Substrate binding. FT METAL 63 63 Magnesium. {ECO:0000305}. FT METAL 66 66 Magnesium. {ECO:0000305}. FT METAL 95 95 Magnesium. {ECO:0000305}. FT METAL 98 98 Magnesium. {ECO:0000305}. FT BINDING 38 38 Substrate. FT BINDING 73 73 Substrate. FT BINDING 102 102 Substrate. FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000250|UniProtKB:Q9H773}. FT MOD_RES 2 2 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9H773}. FT MUTAGEN 38 38 H->A: Reduces affinity for substrate and FT catalytic activity by about 50%. FT {ECO:0000269|PubMed:17320107}. FT MUTAGEN 47 47 W->I: Reduces affinity for substrate and FT catalytic activity by about 50%. FT {ECO:0000269|PubMed:17320107}. FT MUTAGEN 63 63 E->Q: Loss of activity. FT {ECO:0000269|PubMed:17320107}. FT MUTAGEN 66 66 E->Q: Loss of activity. FT {ECO:0000269|PubMed:17320107}. FT MUTAGEN 73 73 W->I: Reduces affinity for substrate and FT catalytic activity by about 50%. FT {ECO:0000269|PubMed:17320107}. FT MUTAGEN 95 95 E->Q: Loss of activity. FT {ECO:0000269|PubMed:17320107}. FT MUTAGEN 98 98 D->N: Loss of activity. FT {ECO:0000269|PubMed:17320107}. FT MUTAGEN 102 102 Y->I: Reduces affinity for substrate and FT catalytic activity by about 50%. FT {ECO:0000269|PubMed:17320107}. FT HELIX 31 43 {ECO:0000244|PDB:2OIE}. FT TURN 44 46 {ECO:0000244|PDB:2OIE}. FT HELIX 48 50 {ECO:0000244|PDB:2OIE}. FT HELIX 53 72 {ECO:0000244|PDB:2OIE}. FT STRAND 76 78 {ECO:0000244|PDB:2A3Q}. FT HELIX 81 83 {ECO:0000244|PDB:2OIE}. FT HELIX 86 109 {ECO:0000244|PDB:2OIE}. FT HELIX 114 119 {ECO:0000244|PDB:2OIE}. FT TURN 120 122 {ECO:0000244|PDB:2OIG}. SQ SEQUENCE 170 AA; 18795 MW; A20ECDA7857446A3 CRC64; MSTAGDGERG TVGQEDSAAA RPFRFSPEPT LEDIRRLHAE FAAERDWEQF HQPRNLLLAL VGEVGELAEL FQWKSDTEPG PQAWPPKERA ALQEELSDVL IYLVALAARC HVDLPQAVIS KMDTNRQRYP VHLSRGSACK YTDLPRGTIS ENQAVGAGDP ASELRDQAST //