NADH pyrophosphatase NudC, Nudix superfamily [Nucleotide transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489204527   2 AGEFRWQAGRPATAQVGGWVLAHCQQRFLQDDNG-LLFPREWLkRQELPLLAEHGVGHWQGEPVYVLELDEPIELP-GMA 79
Cdd:COG2816   15 AAELRADPDWLAAWADPRVLVVDGGRLLLLEDGGeLLLPAGEA-ADLGPPAEAVFLGLDDGRPVFAVDLPAELELPeGAE 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489204527  80 WAPLRQFMLHGDFDQFCMLGYASQIGIWARHNRFCGNCGTRMQAQDHERVMQCPQCGLHQYPRLSPSMIVLVTRGDEVLL 159
Cdd:COG2816   94 FVDLRELGGLLDPRDAGLAARAVALLNWHRTHRFCGRCGAPTVVAAAGWARRCPACGAEHYPRTDPAVIVLVTDGDRILL 173

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489204527 160 ARSPRFVPGVYSTLAGFVEAGESVEQCVvrevreevgvevA------------NLEYIGSQNWPFPHSLMLGFHAEYVSG 227
Cdd:COG2816  174 ARQARWPPGRYSLLAGFVEPGETLEQAV------------RrevfeevgvrvkNVRYVGSQPWPFPSSLMLGFTAEADSG 241

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 489204527 228 EIVPQEDEIEDAQWFSLDALPP------LPAQRSIARHLIDLYLARR 268
Cdd:COG2816  242 EITVDGDEIEDARWFSRDELPAalagllLPPPGSIARRLIEAWLAGP 288

NADH pyrophosphatase-like rudimentary NUDIX domain; The N-terminal domain in NADH pyrophosphatase, which has a rudiment Nudix fold according to SCOP.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489204527   17 VGGWVLAHCQQRFLQ--DDNGLLFPREWLKRQELPLLAEHGVGHWQGEPVYVLELDEPIEL---PGMAWAPLRQFMLHGD 91
Cdd:pfam09296   1 SARWLLFWGGRLLLKkeGDNRLLLPAGELPELVLDLTEPVFLGLDEGAPVFAVDVSAAAELalpEGGEFADLRALMLALD 80

                          90
                  ....*....|....*.
gi 489204527   92 FDQFCMLGYASQIGIW 107
Cdd:pfam09296  81 AEDAGLAAQARALLYW 96

NADH pyrophosphatase NudC, Nudix superfamily [Nucleotide transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489204527   2 AGEFRWQAGRPATAQVGGWVLAHCQQRFLQDDNG-LLFPREWLkRQELPLLAEHGVGHWQGEPVYVLELDEPIELP-GMA 79
Cdd:COG2816   15 AAELRADPDWLAAWADPRVLVVDGGRLLLLEDGGeLLLPAGEA-ADLGPPAEAVFLGLDDGRPVFAVDLPAELELPeGAE 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489204527  80 WAPLRQFMLHGDFDQFCMLGYASQIGIWARHNRFCGNCGTRMQAQDHERVMQCPQCGLHQYPRLSPSMIVLVTRGDEVLL 159
Cdd:COG2816   94 FVDLRELGGLLDPRDAGLAARAVALLNWHRTHRFCGRCGAPTVVAAAGWARRCPACGAEHYPRTDPAVIVLVTDGDRILL 173

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489204527 160 ARSPRFVPGVYSTLAGFVEAGESVEQCVvrevreevgvevA------------NLEYIGSQNWPFPHSLMLGFHAEYVSG 227
Cdd:COG2816  174 ARQARWPPGRYSLLAGFVEPGETLEQAV------------RrevfeevgvrvkNVRYVGSQPWPFPSSLMLGFTAEADSG 241

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 489204527 228 EIVPQEDEIEDAQWFSLDALPP------LPAQRSIARHLIDLYLARR 268
Cdd:COG2816  242 EITVDGDEIEDARWFSRDELPAalagllLPPPGSIARRLIEAWLAGP 288

NADH pyrophosphatase-like rudimentary NUDIX domain; The N-terminal domain in NADH pyrophosphatase, which has a rudiment Nudix fold according to SCOP.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489204527   17 VGGWVLAHCQQRFLQ--DDNGLLFPREWLKRQELPLLAEHGVGHWQGEPVYVLELDEPIEL---PGMAWAPLRQFMLHGD 91
Cdd:pfam09296   1 SARWLLFWGGRLLLKkeGDNRLLLPAGELPELVLDLTEPVFLGLDEGAPVFAVDVSAAAELalpEGGEFADLRALMLALD 80

                          90
                  ....*....|....*.
gi 489204527   92 FDQFCMLGYASQIGIW 107
Cdd:pfam09296  81 AEDAGLAAQARALLYW 96

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489204527 149 VLVTRGDEVLLA-RSPRFVPGVYSTLAGFVEAGESVEQCVVRevreevgvEVANLEYIGSQNWPFP-HSLMLGFHAEYVS 226
Cdd:COG1051   12 VIFRKDGRVLLVrRADEPGKGLWALPGGKVEPGETPEEAALRelreetglEVEVLELLGVFDHPDRgHVVSVAFLAEVLS 91

                         90       100       110
                 ....*....|....*....|....*....|....
gi 489204527 227 GEIVPqEDEIEDAQWFSLDALPPLPAQRSIARHL 260
Cdd:COG1051   92 GEPRA-DDEIDEARWFPLDELPELAFTPADHEIL 124

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 489204527 145 PSMIVLVTRGDEVLLARSPRFVPGVYSTLAGFVEAGESVEQCVVREVREEVGVEVANLEYIGSQNWPFPHSLMLGFHAEy 224
Cdd:cd18884   10 PVVAAIVEHDGHIVLARNKAWPEGWYGLVTGFLEAGESPEEAVLREVKEELGLDGHEAKFIGHYAFPERNQLIIAYHVR- 88

                         90       100
                 ....*....|....*....|....*...
gi 489204527 225 VSGEIVpQEDEIEDAQWFSLDALPPLPA 252
Cdd:cd18884   89 ARGNVK-LNEELDDYKIVPIDKLRPWPF 115

CDP-Choline Pyrophosphatase and similar proteins; Members include: CDP-Choline Pyrophosphatase, ADP-ribose pyrophosphatase, and UDP-X diphosphatase. CDP-choline pyrophosphatase catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. ADP-ribose pyrophosphatase catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. UDP-X diphosphatase hydrolyzes UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-alanine. 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
                 ....*....|....*....|....*....|....*....|....*.
gi 489204527 220 FHAEYVSGEivPQE-DEIEDAQWFSLDALPPLPAQRSIARHLIDLY 264
Cdd:cd04672   83 FLCELIGGE--AQTsIETSEVGFFALDDLPPLSLGRVTPEQIERLF 126

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 489204527 148 IVLVTRGDEVL-LARSPRFVPGVYSTLAGFVEAGESVEQCVVREVREEVGVEVANLEYIGSQNWP----FPHSLMLGFHA 222
Cdd:cd18886    4 LCFIIRDDEVLlLNRNKKPNMGKWNGVGGKLEPGESPEECAIREVFEETGLELEDLQLRGIVTFPsfdgGEDWLMYVFLA 83

                         90       100
                 ....*....|....*....|....*....
gi 489204527 223 EYVSGEIVPQEDEiEDAQWFSLDALPPLP 251
Cdd:cd18886   84 EAFSGELVESDRE-GILAWVPIDWLLNLP 111

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 489204527 148 IVLVTRGDEVLLA-RSPRFVPGVYSTLAGFVEAGESVEQCVVR------EVREEVGVEVANLEYIGSQNWpfPHSLMLGF 220
Cdd:cd02883    5 AVVFDDEGRVLLVrRSDGPGPGGWELPGGGVEPGETPEEAAVRevreetGLDVEVLRLLGVYEFPDPDEG--RHVVVLVF 82

                         90       100
                 ....*....|....*....|....
gi 489204527 221 HAEYVSGEI-VPQEDEIEDAQWFS 243
Cdd:cd02883   83 LARVVGGEPpPLDDEEISEVRWVP 106

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 489204527 109 RHNRFCGnCGTRMQAQDhervmqcpQCGLHQyprlsPSMIVLVTRGDEVLLAR---SPRFVPGVYSTLA-GFVEAGESVE 184
Cdd:cd04697    6 ENNEVVG-AATRAEMRR--------QKLIHR-----ATYIVVRNAAGRLLVQKrtmDKDYCPGYLDPATgGVVGAGESYE 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489204527 185 QCVVREVREEVGVEVANLEYIGSQnwPF---PHSLMLGFHAEYVSGEIVPQEDEIEDAQWFSLDALPPLPAQRSI---AR 258
Cdd:cd04697   72 ENARRELEEELGIDGVPLRPLFTF--YYeddRSRVWGALFECVYDGPLKLQPEEVAEVDWMSEDEILQAARGEEFtpdGR 149

                 ....*...
gi 489204527 259 HLIDLYLA 266
Cdd:cd04697  150 VALERYLA 157

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 489204527 148 IVLVTRGDEVLL---ARSPRfvPGVYSTLAGFVEAGESVEQCVVREVREE------VGVEVANLEYIGSQNWPFP--HSL 216
Cdd:cd04673    5 GAVVFRDGRVLLvrrGNPPD--AGLWSFPGGKVELGETLEDAALRELREEtgleaeVVGLLTVVDVIERDEAGRVrfHYV 82

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 489204527 217 MLGFHAEYVSGEIVPqEDEIEDAQWFSLDALPPLP 251
Cdd:cd04673   83 ILDFLAEWVSGEPVA-GDDALDARWFSLEELDGLP 116

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
                 ....*....|....*....|....*....|....*...
gi 489204527 228 EIVPQEDEIEDAQWFSLDALPPLPAQRSIARHLIDLYL 265
Cdd:cd04670   92 EIKICPEEIAEAKWMPLEEYLKQPNVSQINKLVAKLLL 129

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
                 ....*....|....*....|....*....|....*....|....*
gi 489204527 211 PFPHSLM-LGFHAEYVSGEIVPQeDEIEDAQWFSLDALPPLPAQR 254
Cdd:cd18889   72 PYAYGIYkIFVLCELLGGEFQPN-IETIESGYFSLDELPPLSEEK 115