ITPA_YEAST
ID ITPA_YEAST Reviewed; 197 AA.
AC P47119; D6VWP0;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Inosine triphosphate pyrophosphatase {ECO:0000255|HAMAP-Rule:MF_03148};
DE Short=ITPase {ECO:0000255|HAMAP-Rule:MF_03148};
DE Short=Inosine triphosphatase {ECO:0000255|HAMAP-Rule:MF_03148};
DE EC=3.6.1.9 {ECO:0000255|HAMAP-Rule:MF_03148, ECO:0000269|PubMed:17090528};
DE AltName: Full=Hydroxylaminopurine sensitivity protein 1;
DE AltName: Full=Non-canonical purine NTP pyrophosphatase {ECO:0000255|HAMAP-Rule:MF_03148};
DE AltName: Full=Non-standard purine NTP pyrophosphatase {ECO:0000255|HAMAP-Rule:MF_03148};
DE AltName: Full=Nucleoside-triphosphate diphosphatase {ECO:0000255|HAMAP-Rule:MF_03148};
DE AltName: Full=Nucleoside-triphosphate pyrophosphatase {ECO:0000255|HAMAP-Rule:MF_03148};
DE Short=NTPase {ECO:0000255|HAMAP-Rule:MF_03148};
GN Name=HAM1 {ECO:0000255|HAMAP-Rule:MF_03148}; OrderedLocusNames=YJR069C;
GN ORFNames=J1811;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8789257;
RX DOI=10.1002/(sici)1097-0061(199601)12:1<17::aid-yea875>3.0.co;2-i;
RA Noskov V.N., Staak K., Shcherbakova P.V., Kozmin S.G., Negishi K.,
RA Ono B.-C., Hayatsu H., Pavlov Y.I.;
RT "HAM1, the gene controlling 6-N-hydroxylaminopurine sensitivity and
RT mutagenesis in the yeast Saccharomyces cerevisiae.";
RL Yeast 12:17-29(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8840504;
RX DOI=10.1002/(sici)1097-0061(199607)12:9<869::aid-yea964>3.0.co;2-1;
RA Huang M.-E., Manus V., Chuat J.-C., Galibert F.;
RT "Analysis of a 62 kb DNA sequence of chromosome X reveals 36 open reading
RT frames and a gene cluster with a counterpart on chromosome XI.";
RL Yeast 12:869-875(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL EMBO J. 15:2031-2049(1996).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [6]
RP FUNCTION.
RX PubMed=9918490;
RA Kozmin S.G., Leroy P., Pavlov Y.I.;
RT "Overexpression of the yeast HAM1 gene prevents 6-N-hydroxylaminopurine
RT mutagenesis in Escherichia coli.";
RL Acta Biochim. Pol. 45:645-652(1998).
RN [7]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [8]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [9]
RP FUNCTION.
RX PubMed=17899088; DOI=10.1007/s00294-007-0152-z;
RA Takayama S., Fujii M., Kurosawa A., Adachi N., Ayusawa D.;
RT "Overexpression of HAM1 gene detoxifies 5-bromodeoxyuridine in the yeast
RT Saccharomyces cerevisiae.";
RL Curr. Genet. 52:203-211(2007).
RN [10]
RP SUBSTRATE SPECIFICITY, FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=17090528; DOI=10.1074/jbc.m608708200;
RA Burgis N.E., Cunningham R.P.;
RT "Substrate specificity of RdgB protein, a deoxyribonucleoside triphosphate
RT pyrophosphohydrolase.";
RL J. Biol. Chem. 282:3531-3538(2007).
CC -!- FUNCTION: Pyrophosphatase that hydrolyzes the non-canonical purine
CC nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate
CC (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triphosphate
CC (dHAPTP) and 5-bromodeoxyuridine 5'-triphosphate (BrdUTP) to their
CC respective monophosphate derivatives. Xanthosine 5'-triphosphate (XTP)
CC is also a potential substrate. The enzyme does not distinguish between
CC the deoxy- and ribose forms. Probably excludes non-canonical purines
CC from RNA and DNA precursor pools, thus preventing their incorporation
CC into RNA and DNA and avoiding chromosomal lesions. {ECO:0000255|HAMAP-
CC Rule:MF_03148, ECO:0000269|PubMed:17090528,
CC ECO:0000269|PubMed:17899088, ECO:0000269|PubMed:9918490}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC phosphate + diphosphate + H(+); Xref=Rhea:RHEA:23996,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58043, ChEBI:CHEBI:61557; EC=3.6.1.9;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23997;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'-
CC deoxyribonucleoside 5'-phosphate + diphosphate + H(+);
CC Xref=Rhea:RHEA:44644, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:65317; EC=3.6.1.9;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148,
CC ECO:0000269|PubMed:17090528};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44645;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148,
CC ECO:0000305|PubMed:17090528};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + ITP = diphosphate + H(+) + IMP; Xref=Rhea:RHEA:29399,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58053, ChEBI:CHEBI:61402; EC=3.6.1.9;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29400;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dITP + H2O = dIMP + diphosphate + H(+); Xref=Rhea:RHEA:28342,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:61194, ChEBI:CHEBI:61382; EC=3.6.1.9;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148,
CC ECO:0000269|PubMed:17090528};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28343;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148,
CC ECO:0000305|PubMed:17090528};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + XTP = diphosphate + H(+) + XMP; Xref=Rhea:RHEA:28610,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57464, ChEBI:CHEBI:61314; EC=3.6.1.9;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28611;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148};
CC Note=Binds 1 divalent metal cation per subunit; can use either Mg(2+)
CC or Mn(2+). {ECO:0000255|HAMAP-Rule:MF_03148};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13.4 uM for dITP {ECO:0000269|PubMed:17090528};
CC KM=26.9 uM for dHAPTP {ECO:0000269|PubMed:17090528};
CC KM=722 uM for dGTP {ECO:0000269|PubMed:17090528};
CC Note=kcat is 33.5 sec(-1) with dITP as substrate (PubMed:17090528).
CC kcat is 23.4 sec(-1) with dHAPTP as substrate (PubMed:17090528). kcat
CC is 20.9 sec(-1) with dGTP as substrate (PubMed:17090528).
CC {ECO:0000269|PubMed:17090528};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_03148}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03148,
CC ECO:0000269|PubMed:14562095}. Nucleus {ECO:0000255|HAMAP-Rule:MF_03148,
CC ECO:0000269|PubMed:14562095}.
CC -!- MISCELLANEOUS: Present with 3490 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the HAM1 NTPase family. {ECO:0000255|HAMAP-
CC Rule:MF_03148}.
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DR EMBL; Z49569; CAA89597.1; -; Genomic_DNA.
DR EMBL; L47993; AAB39295.1; -; Genomic_DNA.
DR EMBL; AY557897; AAS56223.1; -; Genomic_DNA.
DR EMBL; BK006943; DAA08856.1; -; Genomic_DNA.
DR PIR; S57088; S57088.
DR RefSeq; NP_012603.1; NM_001181727.1.
DR AlphaFoldDB; P47119; -.
DR SMR; P47119; -.
DR BioGRID; 33826; 56.
DR DIP; DIP-5491N; -.
DR IntAct; P47119; 5.
DR MINT; P47119; -.
DR STRING; 4932.YJR069C; -.
DR iPTMnet; P47119; -.
DR MaxQB; P47119; -.
DR PaxDb; P47119; -.
DR PRIDE; P47119; -.
DR EnsemblFungi; YJR069C_mRNA; YJR069C; YJR069C.
DR GeneID; 853532; -.
DR KEGG; sce:YJR069C; -.
DR SGD; S000003830; HAM1.
DR VEuPathDB; FungiDB:YJR069C; -.
DR eggNOG; KOG3222; Eukaryota.
DR GeneTree; ENSGT00390000015399; -.
DR HOGENOM; CLU_082080_1_1_1; -.
DR InParanoid; P47119; -.
DR OMA; DCFADDT; -.
DR BioCyc; YEAST:G3O-31702-MON; -.
DR Reactome; R-SCE-74259; Purine catabolism.
DR PRO; PR:P47119; -.
DR Proteomes; UP000002311; Chromosome X.
DR RNAct; P47119; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0008828; F:dATP pyrophosphohydrolase activity; IDA:SGD.
DR GO; GO:0047840; F:dCTP diphosphatase activity; IDA:SGD.
DR GO; GO:0036217; F:dGTP diphosphatase activity; IDA:SGD.
DR GO; GO:0035870; F:dITP diphosphatase activity; IDA:SGD.
DR GO; GO:0036218; F:dTTP diphosphatase activity; IDA:SGD.
DR GO; GO:0004170; F:dUTP diphosphatase activity; IDA:SGD.
DR GO; GO:0036219; F:GTP diphosphatase activity; IDA:SGD.
DR GO; GO:0036220; F:ITP diphosphatase activity; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035529; F:NADH pyrophosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0047429; F:nucleoside-triphosphate diphosphatase activity; IBA:GO_Central.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0036221; F:UTP diphosphatase activity; IDA:SGD.
DR GO; GO:0036222; F:XTP diphosphatase activity; IDA:SGD.
DR GO; GO:0009143; P:nucleoside triphosphate catabolic process; IBA:GO_Central.
DR GO; GO:0009117; P:nucleotide metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0009217; P:purine deoxyribonucleoside triphosphate catabolic process; IDA:SGD.
DR GO; GO:0009213; P:pyrimidine deoxyribonucleoside triphosphate catabolic process; IDA:SGD.
DR CDD; cd00515; HAM1; 1.
DR Gene3D; 3.90.950.10; -; 1.
DR HAMAP; MF_03148; HAM1_NTPase; 1.
DR InterPro; IPR002637; Ham1p-like.
DR InterPro; IPR027502; ITPase.
DR InterPro; IPR029001; ITPase-like_fam.
DR PANTHER; PTHR11067; PTHR11067; 1.
DR Pfam; PF01725; Ham1p_like; 1.
DR SUPFAM; SSF52972; SSF52972; 1.
DR TIGRFAMs; TIGR00042; TIGR00042; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; Magnesium; Manganese; Metal-binding;
KW Nucleotide metabolism; Nucleotide-binding; Nucleus; Reference proteome.
FT CHAIN 1..197
FT /note="Inosine triphosphate pyrophosphatase"
FT /id="PRO_0000178279"
FT BINDING 10..15
FT /ligand="ITP"
FT /ligand_id="ChEBI:CHEBI:61402"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03148"
FT BINDING 45
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03148"
FT BINDING 58
FT /ligand="ITP"
FT /ligand_id="ChEBI:CHEBI:61402"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03148"
FT BINDING 76..77
FT /ligand="ITP"
FT /ligand_id="ChEBI:CHEBI:61402"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03148"
FT BINDING 93
FT /ligand="ITP"
FT /ligand_id="ChEBI:CHEBI:61402"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03148"
FT BINDING 151..154
FT /ligand="ITP"
FT /ligand_id="ChEBI:CHEBI:61402"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03148"
FT BINDING 175
FT /ligand="ITP"
FT /ligand_id="ChEBI:CHEBI:61402"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03148"
FT BINDING 180..181
FT /ligand="ITP"
FT /ligand_id="ChEBI:CHEBI:61402"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03148"
SQ SEQUENCE 197 AA; 22093 MW; 1C7AA19465467C07 CRC64;
MSNNEIVFVT GNANKLKEVQ SILTQEVDNN NKTIHLINEA LDLEELQDTD LNAIALAKGK
QAVAALGKGK PVFVEDTALR FDEFNGLPGA YIKWFLKSMG LEKIVKMLEP FENKNAEAVT
TICFADSRGE YHFFQGITRG KIVPSRGPTT FGWDSIFEPF DSHGLTYAEM SKDAKNAISH
RGKAFAQFKE YLYQNDF
