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 47682713  41 SVLVPLLARGGKLYLMFTVRSDKLKREPGEVCFPGGKRDPVDTDDTATALREAQEEVGLHPHQVEVVSHLVPYVFDNDAL 120
Cdd:cd03426   4 AVLIPLVEGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSGFV 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 47682713 121 VTPVVGFLDHNFQAQPNADEVKEVFFVPLDYFLHPQVYYQKQITQSGRD--FIMHCFEYKDpetgvnYLIQGMT 192
Cdd:cd03426  84 VTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGPRgtYRVPFYPYEG------YVIWGLT 151

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 47682713  41 SVLVPLLARGGKLYLMFTVRSDKLKREPGEVCFPGGKRDPVDTDDTATALREAQEEVGLHPHQVEVVSHLVPYVFDNDAL 120
Cdd:cd03426   4 AVLIPLVEGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSGFV 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 47682713 121 VTPVVGFLDHNFQAQPNADEVKEVFFVPLDYFLHPQVYYQKQITQSGRD--FIMHCFEYKDpetgvnYLIQGMT 192
Cdd:cd03426  84 VTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGPRgtYRVPFYPYEG------YVIWGLT 151

8-oxo-dGTP pyrophosphatase MutT and related house-cleaning NTP pyrophosphohydrolases, NUDIX family [Defense mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47682713  41 SVLVPLLARGGKLYLmftVRSDKLKREPGEVCFPGGKRDPVDTDdTATALREAQEEVGLHPHQVEVVSHLVPYVFDnDAL 120
Cdd:COG0494  15 AVVVVLLDDDGRVLL---VRRYRYGVGPGLWEFPGGKIEPGESP-EEAALRELREETGLTAEDLELLGELPSPGYT-DEK 89

                        90       100       110
                ....*....|....*....|....*....|....*
gi 47682713 121 VTPVVG-FLDHNFQAQPNA-DEVKEVFFVPLDYFL 153
Cdd:COG0494  90 VHVFLArGLGPGEEVGLDDeDEFIEVRWVPLDEAL 124

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 47682713  41 SVLVPLLARGGKLYLMFTVRSDKLKREPGEVCFPGGKRDPVDTDDTATALREAQEEVGLHPHQVEVVSHLVPYVFDNDAL 120
Cdd:cd03426   4 AVLIPLVEGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSGFV 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 47682713 121 VTPVVGFLDHNFQAQPNADEVKEVFFVPLDYFLHPQVYYQKQITQSGRD--FIMHCFEYKDpetgvnYLIQGMT 192
Cdd:cd03426  84 VTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGPRgtYRVPFYPYEG------YVIWGLT 151

nudix hydrolase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47682713   34 HLSSNKFSVLVPLLAR----GGKLYLMFTVRSDKLKREPGEVCFPGGKRDPVDTDDTATALREAQEEVGLHPHQVEVVSH 109
Cdd:PLN02709  28 HFPAKSSAVLVCLYQEqredKNELRVILTKRSSTLSSHPGEVALPGGKRDEEDKDDIATALREAREEIGLDPSLVTIISV 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47682713  110 LVPYVFDNDALVTPVVGFL--DHNFQAQPNADEVKEVFFVPLDYFLHPQVYYQKQITQSGRDFIMHCFEYKDPETGVNYL 187
Cdd:PLN02709 108 LEPFVNKKGMSVAPVIGFLhdKKAFKPLPNPAEVEEIFDVPLEMFLKDKNKRAEEREHEGERYLLQYFDYYSEDKERNFI 187

                        170       180
                 ....*....|....*....|....
gi 47682713  188 IQGMTSKLAVLVALIILEQSPAFK 211
Cdd:PLN02709 188 IWALTAGILIRVASIVYQRLPEFQ 211

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47682713    41 SVLVPLLARGGKLYLmftVRSdKLKREPGEVCFPGGKrdpVDTDDT--ATALREAQEEVGLHPHQVEVVSHL-----VPY 113
Cdd:pfam00293   5 AVGVVLLNEKGRVLL---VRR-SKKPFPGWWSLPGGK---VEPGETpeEAARRELEEETGLEPELLELLGSLhylapFDG 77

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 47682713   114 VFDNDALVTPVVGFLDHNFQAQPNADEVKEVFFVPLD 150
Cdd:pfam00293  78 RFPDEHEILYVFLAEVEGELEPDPDGEVEEVRWVPLE 114

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 47682713  68 PGEVCFPGGKRDpvdTDDTA--TALREAQEEVGLHPHQVEVVShlvpyVFDNDALV---TPVVGFLDHNFQAQPNADEVK 142
Cdd:cd18877  46 GGTWALPGGARD---SGETPeaAALRETEEETGLDADTLRVVG-----THVDDHGGwsyTTVLASAPEPLPVRPANEESV 117

                        90
                ....*....|....*..
gi 47682713 143 EVFFVPLD----YFLHP 155
Cdd:cd18877 118 ELRWVPLDevesLPLHP 134

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 47682713  55 LMFTVRSdklkREP--GEVCFPGGKRDPVDTDDTAtALREAQEEVGLHPHQVEVVSHLvP--YVFDNDALVTPVVGF--- 127
Cdd:cd04681  19 ILFVRRA----KEPgkGKLDLPGGFVDPGESAEEA-LRRELREELGLKIPKLRYLCSL-PntYLYKGITYKTCDLFFtae 92

                        90       100
                ....*....|....*....|...
gi 47682713 128 LDHNFQAQPNADEVKEVFFVPLD 150
Cdd:cd04681  93 LDEKPKLKKAEDEVAELEWLDLE 115

MutT homolog-1 (MTH1); MutT homolog-1 (MTH1; EC 3.6.1.- ), also called 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 47682713  74 PGGKRDPVDTDDTAtALREAQEEVGLHPHQVEVVSHLVpYVFDNDALVTPVVGFLDHNFQAQPNA-DEVKEVFF----VP 148
Cdd:cd03427  32 FGGKVEPGETIEEA-AVRELEEEAGLTATELEKVGRLK-FEFPDDPEAMDVHVFRADSWTGEPQEtEEMRPQWFdlddIP 109

                ..
gi 47682713 149 LD 150
Cdd:cd03427 110 YD 111

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 47682713  73 FPGGKRDPvDTDDTATALREAQEEVGLHPhqveVVSHLVPY-VFDNDA------LVTPVVGFLDHNFQAQPNAdEVKEVF 145
Cdd:cd04690  27 LPGGKREP-GETPLQALVRELKEELGLDL----DPDSLRFLgTFEAPAanepgtTVRMTCFTADYDGEPQPAA-EIEELR 100

                ....*
gi 47682713 146 FVPLD 150
Cdd:cd04690 101 WLDPA 105

ADP-ribose pyrophosphatase, UDP-glucose pyrophosphatase, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) ( NUDIX (Nucleoside diphosphate-linked moiety X)) motif 5; Nudt5) 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47682713  73 FPGGKRDPvDTDDTATALREAQEEVGLHPHQVEVVSHLVPyvfdndalvTPvvGFLD---HNFQA---------QPNADE 140
Cdd:cd03424  33 LPAGKIDP-GEDPEEAARRELEEETGYTAGDLELLGSFYP---------SP--GFSDeriHLFLAedltpvseqALDEDE 100

                        90
                ....*....|
gi 47682713 141 VKEVFFVPLD 150
Cdd:cd03424 101 FIEVVLVPLE 110

diadenosine hexaphosphate (Ap6A) hydrolase; Diadenosine hexaphosphate (Ap6A) hydrolase is a member of the NUDIX hydrolase superfamily. Ap6A hydrolase specifically hydrolyzes diadenosine polyphosphates, but not ATP or diadenosine triphosphate, and it generates ATP as the product. Ap6A, the most preferred substrate, hydrolyzes to produce two ATP molecules, which is a novel hydrolysis mode for Ap6A. These results indicate that Ap6A hydrolase is a diadenosine polyphosphate hydrolase. It requires the presence of a divalent cation, such as Mn2+, Mg2+, Zn2+, and Co2+, for activity. Members of the NUDIX hydrolase superfamily 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47682713  65 KREPGEVCF-----------PGGKRDPvdtDDT--ATALREAQEEVGLhphQVEVVSHLVP--YVFDNDALVTP------ 123
Cdd:cd03673  12 RGGGGEVLLihrpryddwslPKGKLEP---GETpeEAAVREVEEETGL---RVRLGRPLGTtrYTYTRKGKGILkkvhyw 85

                        90       100
                ....*....|....*....|....*..
gi 47682713 124 VVGFLDHNFQAQPNaDEVKEVFFVPLD 150
Cdd:cd03673  86 LMRALGGEFLPQPE-EEIDEVRWLPPD 111