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 446680255   6 VTYAILYDKTNeKILMVK-NKGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEAFFEERDHHAIFF 84
Cdd:cd02883    2 AVGAVVFDDEG-RVLLVRrSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEGRHVVVL 80

                         90       100
                 ....*....|....*....|....*
gi 446680255  85 NFLGEIIGGETYISRPKEIEEITWM 109
Cdd:cd02883   81 VFLARVVGGEPPPLDDEEISEVRWV 105

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 446680255   6 VTYAILYDKTNeKILMVK-NKGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEAFFEERDHHAIFF 84
Cdd:cd02883    2 AVGAVVFDDEG-RVLLVRrSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEGRHVVVL 80

                         90       100
                 ....*....|....*....|....*
gi 446680255  85 NFLGEIIGGETYISRPKEIEEITWM 109
Cdd:cd02883   81 VFLARVVGGEPPPLDDEEISEVRWV 105

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446680255    9 AILYDkTNEKILMVK-NKGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEAFFEE----RDHHAIF 83
Cdd:pfam00293   8 VVLLN-EKGRVLLVRrSKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFdgrfPDEHEIL 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 446680255   84 FNFLGEiIGGETYISRPKEIEEITWMELHIAAPYLRIPEH 123
Cdd:pfam00293  87 YVFLAE-VEGELEPDPDGEVEEVRWVPLEELLLLKLAPGD 125

nucleoside triphosphatase YtkD; The functional assignment to the proteins of this family is contentious, with papers disagreeing in both interpretation and enzyme assay results. This protein belongs to the nudix family and shares some sequence identity with E. coli MutT but appears not to be functionally interchangeable with it. [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30
                  ....*....|....*....|....*....|
gi 446680255   32 YTLPGGAVKLGETLEEAVIREVKEETGLHI 61
Cdd:TIGR02705  47 LEFPGGKVEPGETSKEAAIREVMEETGAIV 76

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 446680255   6 VTYAILYDKTNeKILMVK-NKGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEAFFEERDHHAIFF 84
Cdd:cd02883    2 AVGAVVFDDEG-RVLLVRrSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEGRHVVVL 80

                         90       100
                 ....*....|....*....|....*
gi 446680255  85 NFLGEIIGGETYISRPKEIEEITWM 109
Cdd:cd02883   81 VFLARVVGGEPPPLDDEEISEVRWV 105

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446680255  16 NEKILMVKNKGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEAFFEERDHHAIFFNFLGEIIGGET 95
Cdd:cd18880   11 DGKLLLVKHRDEGGIFYILPGGGQEHGETLPEALKRECLEETGLDVEVGDLLFVREYIGPNKPVHQVELFFLCTLEGGEL 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 446680255  96 YISRPKE--IEEITWM---ELHiaapYLRI-PEHLLDLLQ 129
Cdd:cd18880   91 TLGSDPDlnQVGVEWIpleELD----SIRLyPAILRELII 126

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 446680255  16 NEKILMVKnkGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEAFF--EERDHHAIFFNFLGEIIGG 93
Cdd:cd04688   12 DGKVLLAR--GEDDDYYRLPGGRVEFGETSEDALVREFKEELGVEVEVVRLLFVVENFFtyDGKPFHEIGFYYLVELSDE 89

                         90
                 ....*....|..
gi 446680255  94 ETYISRPKEIEE 105
Cdd:cd04688   90 ALYEQDIFFLEE 101

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446680255   9 AILYDKTNEkILMVKNKGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSIseaffeeRDHHA------- 81
Cdd:cd04670    7 GLVINENNE-VLVVQEKYGGPGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGF-------RHQHPgrfgksd 78

                         90       100       110
                 ....*....|....*....|....*....|
gi 446680255  82 IFFNFLGEIIGGETYISRPKEIEEITWMEL 111
Cdd:cd04670   79 LYFVCRLRPLSDEEIKICPEEIAEAKWMPL 108

MutT homolog 2; MutT Homolog 2 (MTH2; EC 3.6.1.9), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 15/Nudt15, may catalyze the hydrolysis of nucleoside diphosphates, triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP, and prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP. MTH2 may also play a role in DNA synthesis and cell cycle progression by stabilizing PCNA. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446680255   9 AILYDKTNeKILMVKNKGENGS-YYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEAFFEERDHHAIFFNFL 87
Cdd:cd04678    7 VIVLNDDG-KVLLGRRKGSHGAgTWALPGGHLEFGESFEECAAREVLEETGLEIRNVRFLTVTNDVFEEEGKHYVTIFVL 85

                         90       100
                 ....*....|....*....|....*
gi 446680255  88 GEIIGGETYISRPKE-IEEITWMEL 111
Cdd:cd04678   86 AEVDDGEPEENMEPDkCEGWEWFSW 110

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 446680255  18 KILMVKNKGENGSYyTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEAFFEERDH---HAIFFNFLGEIIGGE 94
Cdd:cd18874   15 KVLLVRSHKWNDLY-GIPGGKVEWGETLEEALKREVKEETGLDITDIRFILVQESINSEEFHkpaHFVFVDYLARTDSSE 93

                         90       100
                 ....*....|....*....|...
gi 446680255  95 TYISrpKEIEEITWMELHIAAPY 117
Cdd:cd18874   94 VVLN--EEAVEYLWVEPEEALKY 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 446680255  18 KILMVKNKGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEaFFEERDHHAIFFNFLGEIIGGE 94
Cdd:cd18875   15 RVLVLDRVKKDWGGYTFPGGHVEPGESFVDSVIREVKEETGLTIKNPELCGIKQ-WINPDGERYIVFLYKTDHFSGE 90

8-oxo-DGDP phosphatase; 8-oxo-DGDP phosphatase (8DGDPP; EC 3.6.1.55), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 18/Nudt18; 2-hydroxy-DADP phosphatase; 7,8-dihydro-8-oxoguanine phosphatase, hydrolyzes 8-oxo-7,8-dihydroguanine (8-oxo-Gua)-containing deoxyribo- and ribonucleoside diphosphates to the monophosphates. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446680255  17 EKILMVKNKGEN--GSYYtLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSIseaffEERDHHAIFFNFLGEIIGGE 94
Cdd:cd04671   12 GEVLMIQEAKRScrGKWY-LPAGRVEPGESIVEAAKREVKEETGLKCEPSTLLSV-----EEAGGSWYRFVFTGNITGGK 85

                         90
                 ....*....|....
gi 446680255  95 TYISRPKEIEEITW 108
Cdd:cd04671   86 LKTPADADSESLQA 99

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 446680255   9 AILYDKTNEKILMVKNKGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEAFFEERDHHaiffnFLG 88
Cdd:cd04669    3 AVLVIYDDDKLLLIRRTKPGEEYYVFPGGGIEPGETPEEAALREAVEELGLDVAVTLITLILRVLNDGTQHY-----FLA 77

                 ....*..
gi 446680255  89 EIIGGET 95
Cdd:cd04669   78 RVITGSF 84

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 446680255   9 AILYDKTNeKILMVKNKGENGSYytLPGGAVKLGETLEEAVIREVKEETGlhINVKGICSISEAFFEE----RDHHAIFf 84
Cdd:cd04680    5 AIVLDDAG-RVLLVRHTYVPGWY--LPGGGVDKGETAEEAARRELREEAG--VVLTGPPRLFGVYFNRrvspRDHVALY- 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 446680255  85 nflgeiIGGETYISRPK----EIEEITWMELH 112
Cdd:cd04680   79 ------RVREFEQTEPPepngEIAEAGFFALD 104

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 446680255  10 ILYDKTNEkILMVKnKGENGSYyTLPGGAVKLGETLEEAVIREVKEETGLHINV 63
Cdd:cd04677   18 IILNEQGR-ILLQK-RTDTGDW-GLPGGAMELGESLEETARREVFEETGLTVEE 68

bifunctional NMN adenylyltransferase/ADP-ribose pyrophosphatase and similar proteins; Bacterial NadM-Nudix is a bifunctional enzyme containing a nicotinamide mononucleotide (NMN) adenylyltransferase (NMNAT) and an ADP-ribose pyrophosphatase (ADPRase) domain. NMNAT was initially identified as an NAD+ synthase that catalyzes the reversible conversion of NMN to NAD+ in the final step of both the de novo biosynthesis and salvage pathways in most organisms across all three kingdoms of life ADPRase is a member of the NUDIX family proteins, catalyzes the metal-induced and concerted general acid-base hydrolysis of ADP ribose (ADPR) into AMP and ribose-5'-phosphate (R5P). Additional members in this cd include bacterial transcriptional regulator, NrtR, which represses the transcription of NAD biosynthetic genes in vitro and adenosine diphosphate ribose (ADPR), as well as NadQ, a NUDIX-like ATP-responsive regulator of NAD biosynthesis. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belong to this superfamily requires a divalent cation, such as Mg2+ or Mn2+ for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, U=I, L or V) which functions as 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 _ "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 446680255  12 YDKTNEKILMVKNKGENGS-YYTLPGGAVKLGETLEEAVIREVKEETGL 59
Cdd:cd18873   12 FDDGELKVLLIKRKNEPFKgGWALPGGFVREDETLEDAARRELREETGL 60

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 446680255   9 AILYDKtNEKILMVKNKGEngSYYTLPGGAVKLGETLEEAVIREVKEETGLHIN---VKGICSIS-EAFFE-ERDHHAIF 83
Cdd:cd04690    5 AVIIIK-DGRLLLVRKRGT--DAFYLPGGKREPGETPLQALVRELKEELGLDLDpdsLRFLGTFEaPAANEpGTTVRMTC 81

                         90       100       110
                 ....*....|....*....|....*....|.
gi 446680255  84 F--NFLGEIIGGetyisrpKEIEEITWMELH 112
Cdd:cd04690   82 FtaDYDGEPQPA-------AEIEELRWLDPA 105

uncharacterized NUDIX hydrolase subfamily; Contains a crystal structure of the NUDIX hydrolase from Enterococcus faecalis, which has an unknown function. 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 446680255   8 YAILYDKTNEKILMVKNKGEngsyYTLPGGAVKLGETLEEAVIREVKEETGLHINVKG-ICSISEAFF-EERD---HHAI 82
Cdd:cd04684   19 YAVIFNDEGKVLLVQTPNGG----YFLPGGGIEPGETPEEALHREVLEETGWEIEIGEfLGNASRYFYsPDYDryyLNIG 94

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 446680255  83 FFnFLGEIIGgetYISRPKEIE-EITWMELHIAAPYLRIPEH 123
Cdd:cd04684   95 YF-YLAELVR---KVSEPTEEDhELVWLPPEEAADLLKHEHH 132

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446680255   9 AILYDKtNEKILMVKN--KGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHI-NVKGICSISEAFFeeRDHHAIFFN 85
Cdd:COG0494   18 VVLLDD-DGRVLLVRRyrYGVGPGLWEFPGGKIEPGESPEEAALRELREETGLTAeDLELLGELPSPGY--TDEKVHVFL 94

                         90       100
                 ....*....|....*....|....*.
gi 446680255  86 FLGEIIGGETYISRPKEIEEITWMEL 111
Cdd:COG0494   95 ARGLGPGEEVGLDDEDEFIEVRWVPL 120

CDP-choline pyrophosphatase; CDP-choline pyrophosphatase catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446680255   3 KVNVTYAILYDKtnEKILMVKNKgENGSYyTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICsiseAFFEERDH--- 79
Cdd:cd18890    2 KVDIRAVVFNDK--EEILLVKEK-EDGKW-TLPGGWADVGYTPTEVAAKEVEEETGLEVSPKKLL----AILDKRKHphp 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 446680255  80 ------HAIFfnFLGEIIGGETyisRPK-EIEEITWMELH 112
Cdd:cd18890   74 pqptyvYKLF--ILCEIEGGEL---KPSfETGEVRFFSEN 108

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 446680255  16 NEKILMVKNKGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLH---INVKGICSISEAFFEERDHH 80
Cdd:cd04663   12 NRELLVFEHPDFPEAGLQVPKGTVEPGESPEEAALRELAEETGLTgarVVVDLGSHDEGFEELHQRWF 79

MutT pyrophosphohydrolase; The MutT pyrophosphohydrolase is a prototypical NUDIX hydrolase that catalyzes the hydrolysis of nucleoside and deoxynucleoside triphosphates (NTPs and dNTPs) by substitution at a beta-phosphorus to yield a nucleotide monophosphate (NMP) and inorganic pyrophosphate (PPi). This enzyme requires two divalent cations for activity; one coordinates the phosphoryl groups of the NTP/dNTP substrate, and the other coordinates to the enzyme. It also contains the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as metal binding and catalytic site. MutT pyrophosphohydrolase is important in preventing errors in DNA replication by hydrolyzing mutagenic nucleotides such as 8-oxo-dGTP (a product of oxidative damage), which can mispair with template adenine during DNA replication, to guanine nucleotides.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446680255   4 VNVTYAILYDktNEKILMVK--NKGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEAFFEERDHHA 81
Cdd:cd03425    1 IEVVAAIIVD--DGRVLIAQrpEGKHLAGLWEFPGGKVEPGETPEQALVRELREELGIEVEVGEPLGTVEHDYPDFHVRL 78

                         90       100       110
                 ....*....|....*....|....*....|
gi 446680255  82 IFfnFLGEIIGGETyisRPKEIEEITWMEL 111
Cdd:cd03425   79 HV--YLCTLWSGEP---QLLEHQELRWVTP 103

nudix hydrolase

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 446680255   3 KVNVTYAILYDktnEKILMVKNKGENG-SYYTLPGGAVKLGETLEEAVIREVKEETGLHIN-VKGICSISEAFFEE 76
Cdd:PLN02325   9 RVAVVVFLLKG---NSVLLGRRRSSIGdSTFALPGGHLEFGESFEECAAREVKEETGLEIEkIELLTVTNNVFLEE 81

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 446680255   3 KVNVTYAILYDktnEKILMVKnkgENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICSIseaffEERDHH-- 80
Cdd:cd18889    2 KIDTRAAIFKD---DKILLVQ---EKDGRWSLPGGWVDVNQSIKENTIKEAKEEAGLDVEPKRIIAV-----LDRNKHnk 70

                         90       100
                 ....*....|....*....|..
gi 446680255  81 --------AIFfnFLGEIIGGE 94
Cdd:cd18889   71 ppyaygiyKIF--VLCELLGGE 90

nucleoside diphosphate-linked moiety X)) motif 17; Nucleoside diphosphate-linked moiety X)) motif 17 (EC 3.6.1.-) encoded by the NUDT17 gene on chromosome 1q21.1 and encodes an enzyme thought to hydrolyse some nucleoside diphosphate derivatives. 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
                 ....*....|....*....|....*...
gi 446680255  34 LPGGAVKLGETLEEAVIREVKEETGLHI 61
Cdd:cd04694   34 PPGGHVELGESLLEAGLRELQEETGLEV 61

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 446680255  19 ILMVKNKGENGS-YYTLPGGAVKLGETLEEAVIREVKEETGLHI 61
Cdd:PRK05379 216 VLLVRRRAEPGKgLWALPGGFLEQDETLLDACLRELREETGLKL 259

mRNA decapping enzyme 2; mRNA decapping enzyme 2 (Dcp2p; EC 3.6.1.62), nucleoside diphosphate linked moiety X))-type motif 20/Nudt20, is required for degradation of mRNAs, both in normal mRNA turnover, and in nonsense-mediated mRNA decay (NMD). Its catalytic subunit, and Dcp1p are the two components of the decapping enzyme complex. Decapping is a key step in both general and nonsense-mediated 5'->3' mRNA-decay pathways. Dcp2p contains an all-alpha helical N-terminal domain and a C-terminal domain which has the NUDIX fold. While decapping is not dependent on the N-terminus of Dcp2p, it does affect its efficiency. Dcp1p binds the N-terminal domain of Dcp2p stimulating the decapping activity of Dcp2p. Decapping permits the degradation of the transcript and is a site of numerous control inputs. It is responsible for nonsense-mediated decay as well as AU-rich element (ARE)-mediated decay. In addition, it may also play a role in the levels of mRNA. Enzymes belonging to the NUDIX hydrolase superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 446680255   9 AILYDKTNEKILMVKNKGENGSYyTLPGGAVKLGETLEEAVIREVKEETGLHI 61
Cdd:cd03672    6 AILLNEDLDKVLLVKGWKSNSSW-GFPKGKINKDESDADCAIREVYEETGFDI 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 446680255  29 GSYYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGIcsisEAFFEERDHHAIFFNFLGEIIGGETYIS-RPKEIEEIT 107
Cdd:cd04693   57 GMWEASTGGSVLAGETSLEAAIRELKEELGIDLDADEL----RPILTIRFDNGFDDIYLFRKDVDIEDLTlQKEEVQDVK 132

                         90       100
                 ....*....|....*....|....*....
gi 446680255 108 WMELhiaapylripEHLLDLLQKKETVPY 136
Cdd:cd04693  133 WVTL----------EEILEMIESGEFIPY 151

nucleoside triphosphatase YtkD; The functional assignment to the proteins of this family is contentious, with papers disagreeing in both interpretation and enzyme assay results. This protein belongs to the nudix family and shares some sequence identity with E. coli MutT but appears not to be functionally interchangeable with it. [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30
                  ....*....|....*....|....*....|
gi 446680255   32 YTLPGGAVKLGETLEEAVIREVKEETGLHI 61
Cdd:TIGR02705  47 LEFPGGKVEPGETSKEAAIREVMEETGAIV 76

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
                 ....*....|....*....|....*....
gi 446680255  34 LPGGAVKLGETLEEAVIREVKEETGLHIN 62
Cdd:cd04674   33 LPGGYIEYGETWQEAAVRELREETGVEAD 61

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 446680255  35 PGGAVKLGETLEEAVIREVKEETGLHINVKGICSISEAFFEERDHHAIFFNFLGEIIGGEtyisrPKEIEEI 106
Cdd:cd03427   32 FGGKVEPGETIEEAAVRELEEEAGLTATELEKVGRLKFEFPDDPEAMDVHVFRADSWTGE-----PQETEEM 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
                 ....*....|....*....|....*....|....*....|....*..
gi 446680255  17 EKILMV--KNKGENGSYYTLPGGAVKLGETLEEAVIREVKEETGLHI 61
Cdd:cd04683   11 DEVLLLrrANTGYDDGWWHLPAGHVEAGETVRAAAVREAKEELGVEI 57

Uncharacterized conserved protein [Function unknown];

                         10        20
                 ....*....|....*....|....*..
gi 446680255  34 LPGGAVKLGETLEEAVIREVKEETGLH 60
Cdd:COG4111    2 LPGGFVREHESLEDAARRWLAEQTGLE 28

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 446680255  31 YYTLPGGAVKLGETLEEAVIREVKEETGLHINVKGICS------------ISEAFFEERDHHAiffnflgeiiGGETYIS 98
Cdd:cd04511   28 YWTLPAGFMELGETTEQGAARETREEAGARVEIGSLYAvyslphisqvyiIFRARLLSPDFSP----------GPESLEV 97

                         90
                 ....*....|...
gi 446680255  99 RPKEIEEITWMEL 111
Cdd:cd04511   98 RLFDEEEIPWDEL 110

Isopentenyldiphosphate isomerase [Lipid transport and metabolism]; Isopentenyldiphosphate isomerase is part of the Pathway/BioSystem: Isoprenoid biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446680255  36 GGAVKLGETLEEAVIREVKEETGLHIN----VKGICSISEAFFEERDHHAIFFNFLGEIIGgeTYISRPKEIEEITWMEl 111
Cdd:COG1443   64 CGHPRAGETYEEAAVRELEEELGITVDddlrPLGTFRYRAVDANGLVENEFCHVFVARLDG--PLTPQPEEVAEVRWVT- 140

                         90       100
                 ....*....|....*....|....*...
gi 446680255 112 hiaapylriPEHLLDLLQKKET--VPYF 137
Cdd:COG1443  141 ---------LEELLALLEAGPEafTPWF 159