DCTP1_MOUSE
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 03-AUG-2022, entry version 137.
DE RecName: Full=dCTP pyrophosphatase 1 {ECO:0000305};
DE EC=3.6.1.12 {ECO:0000269|PubMed:17320107, ECO:0000269|PubMed:19220460};
DE AltName: Full=Deoxycytidine-triphosphatase 1;
DE Short=dCTPase 1;
DE AltName: Full=RS21-C6 {ECO:0000312|EMBL:AAF15970.1};
GN Name=Dctpp1 {ECO:0000312|MGI:MGI:1913672};
GN Synonyms=Tdrg-TL1 {ECO:0000312|EMBL:AAF15970.1};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
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., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE 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 project:
RT 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 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 5-METHYL
RP DCTP, SUBUNIT, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, MUTAGENESIS OF HIS-38; TRP-47; GLU-63;
RP GLU-66; TRP-73; GLU-95; ASP-98 AND TYR-102, AND MAGNESIUM-BINDING.
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., 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 for
CC dCTP and its analogs including 5-iodo-dCTP and 5-methyl-dCTP for which
CC it may even have a higher efficiency. May protect DNA or RNA against
CC the incorporation of these genotoxic nucleotide analogs through their
CC catabolism. {ECO:0000269|PubMed:17320107, ECO:0000269|PubMed:19220460}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dCTP + H2O = dCMP + diphosphate + H(+); Xref=Rhea:RHEA:22636,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57566, ChEBI:CHEBI:61481; EC=3.6.1.12;
CC Evidence={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 -!- ACTIVITY REGULATION: Inhibited by divalent calcium or cadmium ions.
CC {ECO:0000269|PubMed:17320107}.
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) {ECO:0000269|PubMed:17320107,
CC ECO:0000269|PubMed:19220460};
CC KM=21.7 uM for 5-bromo-dCTP (at pH 8.0) {ECO:0000269|PubMed:17320107,
CC 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) {ECO:0000269|PubMed:17320107,
CC ECO:0000269|PubMed:19220460};
CC Note=Activity is higher with 5-iodo-dCTP, followed by 5-bromo-dCTP,
CC dCTP, 5-methyl-dCTP and 5-chloro-dCTP. Hydrolyzes 2-chloro-dATP and
CC 2-hydroxy-dATP with lower efficiency, and has even lower activity
CC with dATP, dTTP and dUTP (in vitro). Does not hydrolyze ATP, UTP,
CC ITP, GTP, dADP, dCDP or dGTP. {ECO:0000269|PubMed:17320107,
CC 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, cytosol {ECO:0000269|PubMed:19220460}.
CC Note=Not detected in mitochondrion and nucleus.
CC {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}.
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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 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 PDB; 6SQW; X-ray; 1.80 A; A/D=1-170.
DR PDB; 6SQY; X-ray; 1.90 A; A/D=1-170.
DR PDB; 6SQZ; X-ray; 1.90 A; A/D=1-170.
DR PDBsum; 2A3Q; -.
DR PDBsum; 2OIE; -.
DR PDBsum; 2OIG; -.
DR PDBsum; 2Q4P; -.
DR PDBsum; 6SQW; -.
DR PDBsum; 6SQY; -.
DR PDBsum; 6SQZ; -.
DR AlphaFoldDB; Q9QY93; -.
DR SMR; Q9QY93; -.
DR BioGRID; 211463; 1.
DR STRING; 10090.ENSMUSP00000047845; -.
DR PhosphoSitePlus; Q9QY93; -.
DR SwissPalm; Q9QY93; -.
DR EPD; Q9QY93; -.
DR MaxQB; Q9QY93; -.
DR PaxDb; Q9QY93; -.
DR PeptideAtlas; Q9QY93; -.
DR PRIDE; Q9QY93; -.
DR ProteomicsDB; 279606; -.
DR Antibodypedia; 1233; 126 antibodies from 24 providers.
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 VEuPathDB; HostDB:ENSMUSG00000042462; -.
DR eggNOG; ENOG502S210; Eukaryota.
DR GeneTree; ENSGT00390000017709; -.
DR HOGENOM; CLU_110454_0_1_1; -.
DR InParanoid; Q9QY93; -.
DR OMA; KMDTNRQ; -.
DR OrthoDB; 1472354at2759; -.
DR PhylomeDB; Q9QY93; -.
DR TreeFam; TF300237; -.
DR BioCyc; MetaCyc:MON-17900; -.
DR BRENDA; 3.6.1.12; 3474.
DR BioGRID-ORCS; 66422; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Dctpp1; mouse.
DR EvolutionaryTrace; Q9QY93; -.
DR PRO; PR:Q9QY93; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9QY93; protein.
DR Bgee; ENSMUSG00000042462; Expressed in epiblast (generic) and 268 other tissues.
DR Genevisible; Q9QY93; MM.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0047840; F:dCTP diphosphatase activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI: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:0006253; P:dCTP catabolic process; ISO:MGI.
DR GO; GO:0042262; P:DNA protection; ISS:UniProtKB.
DR GO; GO:0009143; P:nucleoside triphosphate catabolic process; IDA:UniProtKB.
DR CDD; cd11537; NTP-PPase_RS21-C6_like; 1.
DR InterPro; IPR025984; DCTPP.
DR Pfam; PF12643; MazG-like; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Hydrolase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9H773"
FT CHAIN 2..170
FT /note="dCTP pyrophosphatase 1"
FT /id="PRO_0000291770"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 150..170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 38
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17320107,
FT ECO:0007744|PDB:2OIG"
FT BINDING 47..51
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17320107,
FT ECO:0007744|PDB:2OIG"
FT BINDING 63
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305|PubMed:17320107"
FT BINDING 66
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305|PubMed:17320107"
FT BINDING 73
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17320107,
FT ECO:0007744|PDB:2OIG"
FT BINDING 95
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305|PubMed:17320107"
FT BINDING 98
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305|PubMed:17320107"
FT BINDING 102
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:17320107"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H773"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H773"
FT MUTAGEN 38
FT /note="H->A: Reduces affinity for substrate and catalytic
FT activity by about 50%."
FT /evidence="ECO:0000269|PubMed:17320107"
FT MUTAGEN 47
FT /note="W->I: Reduces affinity for substrate and catalytic
FT activity by about 50%."
FT /evidence="ECO:0000269|PubMed:17320107"
FT MUTAGEN 63
FT /note="E->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17320107"
FT MUTAGEN 66
FT /note="E->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17320107"
FT MUTAGEN 73
FT /note="W->I: Reduces affinity for substrate and catalytic
FT activity by about 50%."
FT /evidence="ECO:0000269|PubMed:17320107"
FT MUTAGEN 95
FT /note="E->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17320107"
FT MUTAGEN 98
FT /note="D->N: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17320107"
FT MUTAGEN 102
FT /note="Y->I: Reduces affinity for substrate and catalytic
FT activity by about 50%."
FT /evidence="ECO:0000269|PubMed:17320107"
FT HELIX 31..44
FT /evidence="ECO:0007829|PDB:6SQW"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:6SQW"
FT HELIX 53..71
FT /evidence="ECO:0007829|PDB:6SQW"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:6SQW"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:6SQW"
FT HELIX 86..109
FT /evidence="ECO:0007829|PDB:6SQW"
FT HELIX 114..128
FT /evidence="ECO:0007829|PDB:6SQW"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:6SQW"
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
