ADP-ribose pyrophosphatase YjhB, NUDIX family [Nucleotide transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  10 FLLIDEDKVLLEQRSKEKRcdPDMVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYHPTSELQLLHYYVVTQ 89
Cdd:COG1051   12 VIFRKDGRVLLVRRADEPG--KGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHPDRGHVVSVAFLAEV 89

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 516401829  90 WQGEIQ-SHEADTVFWskvtdfAPATEVDKIALKELLR 126
Cdd:COG1051   90 LSGEPRaDDEIDEARW------FPLDELPELAFTPADH 121

ADP-ribose pyrophosphatase YjhB, NUDIX family [Nucleotide transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  10 FLLIDEDKVLLEQRSKEKRcdPDMVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYHPTSELQLLHYYVVTQ 89
Cdd:COG1051   12 VIFRKDGRVLLVRRADEPG--KGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHPDRGHVVSVAFLAEV 89

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 516401829  90 WQGEIQ-SHEADTVFWskvtdfAPATEVDKIALKELLR 126
Cdd:COG1051   90 LSGEPRaDDEIDEARW------FPLDELPELAFTPADH 121

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  15 EDKVLLEQRSKEkrCD-PDMVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYHPTSELQL-LHYYVVTQWQG 92
Cdd:PRK10546  14 DGKILLAQRPAH--SDqAGLWEFAGGKVEPGESQPQALIRELREELGIEATVGEYVASHQREVSGRRIhLHAWHVPDFHG 91

                         90
                 ....*....|..
gi 516401829  93 EIQSHEADTVFW 104
Cdd:PRK10546  92 ELQAHEHQALVW 103

ADP-ribose pyrophosphatase YjhB, NUDIX family [Nucleotide transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  10 FLLIDEDKVLLEQRSKEKRcdPDMVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYHPTSELQLLHYYVVTQ 89
Cdd:COG1051   12 VIFRKDGRVLLVRRADEPG--KGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHPDRGHVVSVAFLAEV 89

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 516401829  90 WQGEIQ-SHEADTVFWskvtdfAPATEVDKIALKELLR 126
Cdd:COG1051   90 LSGEPRaDDEIDEARW------FPLDELPELAFTPADH 121

NUDIX hydrolase superfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829   6 PCVSFLLIDE-DKVLLEQRSKEKrcDPDMVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYHPTSEL---QL 81
Cdd:cd02883    1 VAVGAVVFDDeGRVLLVRRSDGP--GPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEgrhVV 78

                         90       100
                 ....*....|....*....|....*.
gi 516401829  82 LHYYVVTQWQGE---IQSHEADTVFW 104
Cdd:cd02883   79 VLVFLARVVGGEpppLDDEEISEVRW 104

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  15 EDKVLLEQRSKEkrCD-PDMVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYHPTSELQL-LHYYVVTQWQG 92
Cdd:PRK10546  14 DGKILLAQRPAH--SDqAGLWEFAGGKVEPGESQPQALIRELREELGIEATVGEYVASHQREVSGRRIhLHAWHVPDFHG 91

                         90
                 ....*....|..
gi 516401829  93 EIQSHEADTVFW 104
Cdd:PRK10546  92 ELQAHEHQALVW 103

8-oxo-dGTP diphosphatase MutT;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  37 PCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYHPTSELQL-LHYYVVTQWQGEIQSHEADTVFWSKVT-----DF 110
Cdd:PRK10776  36 PGGKIEAGETPEQALIRELQEEVGITVQHATLFEKLEYEFPDRHItLWFWLVESWEGEPWGKEGQPGRWVSQValnadEF 115

                 ....*
gi 516401829 111 APATE 115
Cdd:PRK10776 116 PPANE 120

ADP-ribose pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase; EC 3.6.1.13) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the NUDIX hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also contains a 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. In humans, there are four distinct ADPRase activities, three putative cytosolic (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). ADPRase-m is also known as NUDT9. It can be distinugished from the cytosolic ADPRase by a N-terminal target sequence unique to mitochondrial ADPRase. NUDT9 functions as a monomer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829   8 VSFLLIDEDKVLLEQRSKEkrcdPD--MVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSL--YHPTSELQLLH 83
Cdd:cd04673    4 VGAVVFRDGRVLLVRRGNP----PDagLWSFPGGKVELGETLEDAALRELREETGLEAEVVGLLTVVdvIERDEAGRVRF 79

                         90
                 ....*....|....*.
gi 516401829  84 YYVVTQWQGEIQSHEA 99
Cdd:cd04673   80 HYVILDFLAEWVSGEP 95

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 516401829   5 HPCVSFLLID--EDKVLLEQRSKEKRCDPDMVAIPC-GHMETGESQTQTLLREISEELGVDA 63
Cdd:cd04692   26 HRTVHVWLVNpeEGRLLLQKRSANKDDFPGLWDISAaGHIDAGETYEEAAVRELEEELGLTV 87

Nudix family hydrolase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829   1 MPPVHPCVSFLLIDEDKVLLEQRSKEKrcdpDMVAI---PCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYH--P 75
Cdd:PRK08999   2 MKRIHVAAGVIRDADGRILLARRPEGK----HQGGLwefPGGKVEPGETVEQALARELQEELGIEVTAARPLITVRHdyP 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 516401829  76 TSELqLLHYYVVTQWQGEIQSHEADTVFWSK-----VTDFAPA 113
Cdd:PRK08999  78 DKRV-RLDVRRVTAWQGEPHGREGQPLAWVApdelaVYPFPPA 119

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 516401829   8 VSFLLIDEDKVLLEQRSKEkrcdPD--MVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSL 72
Cdd:cd04681    9 VGVIIRNEGEILFVRRAKE----PGkgKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYLCSL 71

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829   7 CVSFLLIDEDKVLLEQRSkekrcDPDMVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYHPTSELQLLH--- 83
Cdd:cd04677   15 AAVIILNEQGRILLQKRT-----DTGDWGLPGGAMELGESLEETARREVFEETGLTVEELELLGVYSGKDLYYTYPNgde 89

                         90       100
                 ....*....|....*....|....*
gi 516401829  84 ------YYVVTQWQGEIQSHEADTV 102
Cdd:cd04677   90 vynvtaVYLVRDVSGELKVDDEESL 114

MutT homolog-1 and similar proteins; MutT homolog-1 (MTH1), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 1/Nudt1, is a member of the NUDIX hydrolase superfamily. MTH1, the mammalian counterpart of MutT, hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-ATP, to monophosphates, thereby preventing the incorporation of such oxygen radicals during replication. This is an important step in the repair mechanism in genomic and mitochondrial DNA. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity, and contain the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. MTH1 is predominantly localized in the cytoplasm and mitochondria. Structurally, this enzyme adopts a similar fold to MutT despite low sequence similarity outside the conserved NUDIX motif. The most distinctive structural difference between MutT and MTH1 is the presence of a beta-hairpin, which is absent in MutT. This results in a much deeper and narrower substrate binding pocket. Mechanistically, MTH1 contains dual specificity for nucleotides that contain 2-OH-adenine bases and those that contain 8-oxo-guanine bases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  11 LLIDEDKVLLEQRSkekRCDPDMVAIPCGHMETGESQTQTLLREISEELGVDALAYH-YLCSLYHPTSELQLLH-YYVVT 88
Cdd:cd04699    8 VIFDNGRVLLLRRS---RAGAGEWELPGGRLEPGESPEEALKREVKEETGLDVSVGElLDTWTFELDPDKGVFIvTYLCR 84

                         90
                 ....*....|.
gi 516401829  89 QWQGEIQ-SHE 98
Cdd:cd04699   85 LVGGEVTlSDE 95

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829   5 HPCVSFLLIDED-KVLLEQRskekrcD-------PDMVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYHPT 76
Cdd:cd18882    1 HEVAIAILYDDRgKVLLQLR------DdkpgipyPGYWGLFGGHLEPGETPEEAIRRELEEEIGYEPGEFRFFLLYTEDD 74

                         90
                 ....*....|.
gi 516401829  77 SELQLLHYYVV 87
Cdd:cd18882   75 GEDRIRHVFHA 85

NUDIX domain family found in Deinococcus radiodurans, and similar proteins; Deinococcus radiodurans protein DR_0079 is one of 21 NUDIX hydrolases that it encodes, and it has been observed to have a marked preference for cytosine ribonucleoside 5'-diphosphate (CDP) and cytosine ribonucleoside 5'-triphosphate (CTP), and for their corresponding deoxyribose nucleotides, dCDP and dCTP, to a lesser degree. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 516401829  10 FLLIDEDKVLLEQRSKEKRCDP---DM-VAipcGHMETGESQTQTLLREISEELGVD--ALAYHYL 69
Cdd:cd24154    8 FLINSQGQLWIPRRTADKRIFPlalDMsVG---GHVSSGETYEQAFVRELQEELNLDldQLSYRVL 70

coenzyme A pyrophosphatase and similar proteins; Coenzyme A pyrophosphatase (CoAse; EC 3.6.1.1), also called nucleoside diphosphate-linked moiety X)) motif 7, is a member of the NUDIX hydrolase superfamily, functions to catalyze the elimination of oxidized inactive CoA, which can inhibit CoA-utilizing enzymes. The need of CoAses mainly arises under conditions of oxidative stress. CoAse has a conserved NUDIX fold and requires a single divalent cation for catalysis. In addition to a signature NUDIX motif G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val, CoAse contains an additional motif upstream called the NuCoA motif (LLTXT(SA)X3RX3GX3FPGG) which is postulated to be involved in CoA recognition. CoA plays a central role in lipid metabolism. It is involved in the initial steps of fatty acid sythesis in the cytosol, in the oxidation of fatty acids and the citric acid cycle in the mitochondria, and in the oxidation of long-chain fatty acids in peroxisomes. CoA has the important role of activating fatty acids for further modification into key biological signalling molecules.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  14 DEDKVLLEQRSKEKRCDPDMVAIPCGHMETG-ESQTQTLLREISEELGVDALAYHYLCSLyhptSELQLLHYYVVT---- 88
Cdd:cd03426   14 GELHVLLTKRASHLRSHPGQIAFPGGKREPGdESPVETALRETEEEIGLPPESVEVLGRL----DPLYTPSGFVVTpfvg 89

                         90       100
                 ....*....|....*....|
gi 516401829  89 QWQGE----IQSHEADTVFW 104
Cdd:cd03426   90 LLDDPpplrPNPDEVAEVFT 109

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 516401829  11 LLIDED-KVLLEQRSKEKRCDpdmvaIPCGHMETGESQTQTLLREISEELGVD 62
Cdd:cd18876    6 LFTDAAgRVLLVKPTYKDGWE-----LPGGVVEAGESPLQAARREVREELGLD 53

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  11 LLIDEDKVLLEQRSK---EKRCDpdmvaIPCGHMETGESQTQTLLREISEELGVDALAYHYL--CSLYHPTS--ELQLLH 83
Cdd:cd04686    7 IIIRNDKLLLIRKTRgpyQGRYD-----LPGGSQEFGESLEDALKREFAEETGMTVTSYDNLgvYDFFVPWSdkELGDVH 81

                         90
                 ....*....|....*..
gi 516401829  84 ----YYVVTQWQGEIQS 96
Cdd:cd04686   82 higvFYDVELLDNNISE 98

dihydroneopterin hydrolase; DHNTP pyrophosphatase (DHNTPase) catalyzes the hydrolysis of dihydroneopterin triphosphate (DHNTP) to dihydroneopterin monophosphate (DHNMP) and pyrophosphate,the second step in the pterin branch of the folate synthesis pathway in bacteria. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 516401829   7 CVSFLLIDEDKVLLEQRSKekrcDPD---MVAipcGHMETGESQTQTLLREISEELGVDALAYHYLCSLYH 74
Cdd:cd04664    5 VVIYRKDEEGEVLLLKRTD----DGGfwqSVT---GGIEDGETPWQAALRELKEETGLDPLELQLIDLNVS 68

ADP-ribose pyrophosphatase and similar proteins; ADP-ribose pyrophosphatase (ADPRase; EC 3.6.1.13) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the NUDIX hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also contains a 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. In humans, there are four distinct ADPRase activities, three putative cytosolic (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). ADPRase-m is also known as NUDT9. It can be distinugished from the cytosolic ADPRase by a N-terminal target sequence unique to mitochondrial ADPRase. NUDT9 functions as a monomer.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829   8 VSFLLIDEDKVLLEQRS----KEKrcdpdmVAIPCGHMETGESQTQTLLREISEELGVDA 63
Cdd:cd04691    4 VGGVVVKEGKVLLVKRAygpgKGR------WTLPGGFVEEGETLDEAIVREVLEETGIDA 57

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  11 LLIDEDKVLLeQRSKekrcDPDMVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSL-----YHPTSELQLLHYY 85
Cdd:cd04688    8 IIIRDGKVLL-ARGE----DDDYYRLPGGRVEFGETSEDALVREFKEELGVEVEVVRLLFVVenfftYDGKPFHEIGFYY 82

                 ...
gi 516401829  86 VVT 88
Cdd:cd04688   83 LVE 85

Antisense Basic Fibroblast Growth Factor; Antisense Basic Fibroblast Growth Factor (ASFGF2; EC 3.6.1.-), also known as nucleoside diphosphate-linked moiety X)) motif 6/Nudt6, and similar proteins including peroxisomal coenzyme A diphosphatase/Nudt7 and mitochondrial coenzyme A diphosphatase/Nudt8. The Nudt6 gene overlaps and lies on the opposite strand from FGF2 gene, and is thought to be the FGF2 antisense gene. The two genes are independently transcribed, and their expression shows an inverse relationship, suggesting that this antisense transcript may regulate FGF2 expression. This gene has also been shown to have hormone-regulatory and antiproliferative actions in the pituitary that are independent of FGF2 expression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 516401829  14 DEDKVLLEQrskEKRCDPDMVAIPCGHMETGESQTQTLLREISEELGVDA 63
Cdd:cd04670   12 ENNEVLVVQ---EKYGGPGGWKLPGGLVDPGEDIGEAAVREVFEETGIDT 58

MutT homolog-1 and similar proteins; MutT homolog-1 (MTH1), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 1/Nudt1, is a member of the NUDIX hydrolase superfamily. MTH1, the mammalian counterpart of MutT, hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-ATP, to monophosphates, thereby preventing the incorporation of such oxygen radicals during replication. This is an important step in the repair mechanism in genomic and mitochondrial DNA. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity, and contain the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. MTH1 is predominantly localized in the cytoplasm and mitochondria. Structurally, this enzyme adopts a similar fold to MutT despite low sequence similarity outside the conserved NUDIX motif. The most distinctive structural difference between MutT and MTH1 is the presence of a beta-hairpin, which is absent in MutT. This results in a much deeper and narrower substrate binding pocket. Mechanistically, MTH1 contains dual specificity for nucleotides that contain 2-OH-adenine bases and those that contain 8-oxo-guanine bases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  13 IDEDKVLLEQRSKekrcDPDMVA--IPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYHPTSELQlLHY----YV 86
Cdd:cd04679   10 LDDGRLLLVLRLR----APEAGHwgLPGGKVDWLETVEDAVRREILEELGLEIELTRLLCVVDQIDAADG-EHWvapvYL 84

                         90
                 ....*....|....
gi 516401829  87 VTQWQGEIQSHEAD 100
Cdd:cd04679   85 AEIFSGEPRLMEPE 98

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829   6 PCVSFLLIDEDKVLLEQrskEKRCDPDMVAIPCGHMETGESQTQTLLREISEELGVDALA 65
Cdd:cd18884   10 PVVAAIVEHDGHIVLAR---NKAWPEGWYGLVTGFLEAGESPEEAVLREVKEELGLDGHE 66

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829   8 VSFLLI--DEDKVLLEQRSKEKRCDPDMV-AIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYH 74
Cdd:cd04697   28 ATYIVVrnAAGRLLVQKRTMDKDYCPGYLdPATGGVVGAGESYEENARRELEEELGIDGVPLRPLFTFYY 97

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  11 LLIDEDKVLLEQRSKEKRcdPDMVaIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLYHPTSELQllHYYV--VT 88
Cdd:cd04669    6 VIYDDDKLLLIRRTKPGE--EYYV-FPGGGIEPGETPEEAALREAVEELGLDVAVTLITLILRVLNDGTQ--HYFLarVI 80

                 ....*
gi 516401829  89 QWQGE 93
Cdd:cd04669   81 TGSFG 85

nucleoside diphosphate-linked moiety X)) motif 16; U8 SnoRNA-decapping enzyme, also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 16/Nudt16, is encoded by the human NUDT16 gene and a RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 516401829  37 PCGHMETGESQTQTLLREISEELGVDALA-----YHYLCSlyHPTSEL--QLLHYY 85
Cdd:cd18869   41 PGGFVDTGESLEEGLNRELREELGLAHAVfpvteDDYRSS--HVREGPkrLVLHFY 94

Isopentenyl diphosphate isomerase; Isopentenyl diphosphate (IPP) isomerase, a member of the NUDIX hydrolase superfamily, is a key enzyme in the isoprenoid biosynthetic pathway. Isoprenoids comprise a large family of natural products including sterols, carotenoids, dolichols and prenylated proteins. These compounds are synthesized from two precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). IPP isomerase catalyzes the interconversion of IPP and DMAPP by a stereoselective antarafacial transposition of hydrogen. The enzyme requires one Mn2+ or Mg2+ ion in its active site to fold into an active conformation and also contains the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. The metal binding site is present within the active site and plays structural and catalytical roles. IPP isomerase is well represented in several bacteria, archaebacteria and eukaryotes, including fungi, mammals and plants. Despite sequence variations (mainly at the N-terminus), the core structure is highly conserved.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516401829  10 FLLIDEDKVLLEQRSKEKR---------CdpdmvaipCGHMETGESQTQTLLREISEELGVDALAYHYLCS-LYHPTSEl 79
Cdd:cd02885   34 FLFNSKGELLLQRRALSKYtwpglwtntC--------CSHPLPGEGVEDAAQRRLREELGIPVCDLEELPRfRYRATDD- 104

                         90       100       110
                 ....*....|....*....|....*....|
gi 516401829  80 qllhyyvvtqwqGEIQSHEADTVFWSKVTD 109
Cdd:cd02885  105 ------------NGLVEHEIDHVFVGRADG 122

Adp Ribose Pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 516401829   5 HPCVSFLLID--EDKVLL-EQ-R--SKEKRCDPDMVAIPCGHMETGESQTQTLLREISEELGVDALAYHYLCSLY 73
Cdd:cd24155   43 GDAVAVLPYDpvRDEVVLiEQfRigALARDESPWLLEIVAGMIDAGETPEDVARREAEEEAGLTLDALEPIASYY 117

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 516401829   4 VHPCVSFLLIDEDKVLLEQRSKEKRcdpdMVAIPCGHMETGESQTQTLLREISEELG 60
Cdd:cd04676   16 FTPSVAAVILNEDGRILLQRKGGLG----LWSLPAGAIEPGEHPAEAVIREVREETG 68

isopentenyl-diphosphate Delta-isomerase;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 516401829   3 PVHPCVSFLLIDED-KVLLEQRSKEKRcdpdmvAIP-------CGHMETGESQTQTLLREISEELGVDA 63
Cdd:PRK03759  32 PLHLAFSCYLFDADgRLLVTRRALSKK------TWPgvwtnscCGHPQPGESLEDAVIRRCREELGVEI 94

dihydroneopterin triphosphate pyrophosphatase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 516401829   1 MPPVHPcVSFLLI--DED-KVLLEQRskekRCDPDMVAIPCGHMETGESQTQTLLREISEELGVDALA 65
Cdd:PRK09438   2 MPYKRP-VSVLVViyTPDlGVLMLQR----ADDPDFWQSVTGSLEEGETPAQTAIREVKEETGIDVLA 64