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 79552110 123 HRIGIGAFVLNKNGEMLVVQENSGYfkdKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFMESHQAVWQrK 202
Cdd:cd04670   1 HQVGVGGLVINENNEVLVVQEKYGG---PGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFRHQHPGRFG-K 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 79552110 203 TDIFFVCELEARTF-EIQKQDSEIHAAKWMPVEEYVNQPYHnkegNEMFKLIANICLK 259
Cdd:cd04670  77 SDLYFVCRLRPLSDeEIKICPEEIAEAKWMPLEEYLKQPNV----SQINKLVAKLLLE 130

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 79552110 123 HRIGIGAFVLNKNGEMLVVQENSGYfkdKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFMESHQAVWQrK 202
Cdd:cd04670   1 HQVGVGGLVINENNEVLVVQEKYGG---PGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFRHQHPGRFG-K 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 79552110 203 TDIFFVCELEARTF-EIQKQDSEIHAAKWMPVEEYVNQPYHnkegNEMFKLIANICLK 259
Cdd:cd04670  77 SDLYFVCRLRPLSDeEIKICPEEIAEAKWMPLEEYLKQPNV----SQINKLVAKLLLE 130

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79552110   123 HRIGIGAFVLNKNGEMLVVQENSGYFKdkNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFMESHQAVWQRK 202
Cdd:pfam00293   2 RRVAVGVVLLNEKGRVLLVRRSKKPFP--GWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRF 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 79552110   203 TD-----IFFVCELEARtfEIQKQDSEIHAAKWMPVEEYVNQPYHN 243
Cdd:pfam00293  80 PDeheilYVFLAEVEGE--LEPDPDGEVEEVRWVPLEELLLLKLAP 123

RNA pyrophosphohydrolase; Reviewed

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 79552110  123 HRIGIGAFVLNKNGEMLVVQEnsgyFKDKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVL 189
Cdd:PRK00714   7 YRPNVGIILLNRQGQVFWGRR----IGQGHSWQFPQGGIDPGETPEQAMYRELYEEVGLRPEDVEIL 69

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 79552110 123 HRIGIGAFVLNKNGEMLVVQENSGYfkdKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFMESHQAVWQrK 202
Cdd:cd04670   1 HQVGVGGLVINENNEVLVVQEKYGG---PGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFRHQHPGRFG-K 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 79552110 203 TDIFFVCELEARTF-EIQKQDSEIHAAKWMPVEEYVNQPYHnkegNEMFKLIANICLK 259
Cdd:cd04670  77 SDLYFVCRLRPLSDeEIKICPEEIAEAKWMPLEEYLKQPNV----SQINKLVAKLLLE 130

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79552110   123 HRIGIGAFVLNKNGEMLVVQENSGYFKdkNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFMESHQAVWQRK 202
Cdd:pfam00293   2 RRVAVGVVLLNEKGRVLLVRRSKKPFP--GWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRF 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 79552110   203 TD-----IFFVCELEARtfEIQKQDSEIHAAKWMPVEEYVNQPYHN 243
Cdd:pfam00293  80 PDeheilYVFLAEVEGE--LEPDPDGEVEEVRWVPLEELLLLKLAP 123

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 79552110 125 IGIGAFVLNKNGEMLVVQENsgYFKDKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVL-SFMESHQAVWQRKT 203
Cdd:cd02883   1 VAVGAVVFDDEGRVLLVRRS--DGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLgVYEFPDPDEGRHVV 78

                        90       100
                ....*....|....*....|....*....
gi 79552110 204 DIFFVCELEARTFEIQkQDSEIHAAKWMP 232
Cdd:cd02883  79 VLVFLARVVGGEPPPL-DDEEISEVRWVP 106

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 79552110 125 IGIGAFVLnKNGEMLVVQENSGYFKDKnvWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFMEshQAVWQRKTD 204
Cdd:cd04691   2 LGVGGVVV-KEGKVLLVKRAYGPGKGR--WTLPGGFVEEGETLDEAIVREVLEETGIDAKPVGIIGVRS--GVIRDGKSD 76

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 79552110 205 IFFVCELEARTFEIQKQDSEIHAAKWMPVEEYVNQP 240
Cdd:cd04691  77 NYVVFLLEYVGGEPKPDERENSEAGFLTLEEALANE 112

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 79552110 124 RIGIGAFVLNKNGEMLVVQENSGYFKDKnvWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFMESHQAVWQRKT 203
Cdd:cd04678   2 RVGVGVIVLNDDGKVLLGRRKGSHGAGT--WALPGGHLEFGESFEECAAREVLEETGLEIRNVRFLTVTNDVFEEEGKHY 79

                        90       100       110
                ....*....|....*....|....*....|...
gi 79552110 204 -DIFFVCELEARTFEIQKQDSEIHAAKWMPVEE 235
Cdd:cd04678  80 vTIFVLAEVDDGEPEENMEPDKCEGWEWFSWDE 112

uncharacterized NUDIX hydrolase subfamily; Contains a crystal structure of the NUDIX hydrolase from Nitrosomonas europaea, 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 79552110 129 AFVLNKNGEMLVVQENSgyfKDKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFMESHQAvwQRKTDIF-- 206
Cdd:cd03675   4 AAVVERDGRFLLVEEET---DGRLVLNQPAGHLEPGESLLEAAIRETLEETGWEVEPTALLGIYQWTAP--DNGVTYLrf 78

                        90       100       110
                ....*....|....*....|....*....|....
gi 79552110 207 -FVCELEARTfEIQKQDSEIHAAKWMPVEEYVNQ 239
Cdd:cd03675  79 aFAGELLEHL-PDQPLDSGIIRAHWLTLEEILAL 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 79552110 128 GAFVLNkNGEMLVVQENsgyfKD--KNVWKVPTGTIKEGESIWAGAVREVKEETDIDaefVEVLSFMES------HQAVW 199
Cdd:cd04681  10 GVIIRN-EGEILFVRRA----KEpgKGKLDLPGGFVDPGESAEEALRRELREELGLK---IPKLRYLCSlpntylYKGIT 81

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 79552110 200 QRKTDIFFVCELEArTFEIQKQDSEIHAAKWMPVEE 235
Cdd:cd04681  82 YKTCDLFFTAELDE-KPKLKKAEDEVAELEWLDLEE 116

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 79552110 131 VLNKNGEMLVVQENSgyfKDKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSfmeshqaVWQRKTD------ 204
Cdd:cd04699   8 VIFDNGRVLLLRRSR---AGAGEWELPGGRLEPGESPEEALKREVKEETGLDVSVGELLD-------TWTFELDpdkgvf 77

                        90       100       110
                ....*....|....*....|....*....|..
gi 79552110 205 -IFFVCELEARTFEIQkqdSEIHAAKWMPVEE 235
Cdd:cd04699  78 iVTYLCRLVGGEVTLS---DEHEEYEWVTPEE 106

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 79552110 123 HRIGIGAFVLNKNGEMLVVQ-ENSGYFkdknvwkVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVL-----SFMESHQ 196
Cdd:cd04684  14 DRPGAYAVIFNDEGKVLLVQtPNGGYF-------LPGGGIEPGETPEEALHREVLEETGWEIEIGEFLgnasrYFYSPDY 86

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 79552110 197 AVWQRKTDIFFVCELEARtfeIQKQDSEIHAAKWMPVEE 235
Cdd:cd04684  87 DRYYLNIGYFYLAELVRK---VSEPTEEDHELVWLPPEE 122

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 79552110 124 RIGIGAFVLnKNGEMLVV--QENSGYFkdknvWKVPTGTIKEGESIWAGAVREVKEETDIDAE---FVEVLSFMESHQAV 198
Cdd:cd18880   1 RIRAKAIII-EDGKLLLVkhRDEGGIF-----YILPGGGQEHGETLPEALKRECLEETGLDVEvgdLLFVREYIGPNKPV 74

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 79552110 199 WQrkTDIFFVCELEARTFEIQK-QDSEIHAAKWMPVEE 235
Cdd:cd18880  75 HQ--VELFFLCTLEGGELTLGSdPDLNQVGVEWIPLEE 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 79552110 127 IGAFVLNKNGEMLVVQENsgyfKDKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFMES--HQAVWQRKTD 204
Cdd:cd18874   5 VGALIFNPDGKVLLVRSH----KWNDLYGIPGGKVEWGETLEEALKREVKEETGLDITDIRFILVQESinSEEFHKPAHF 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 79552110 205 IF--FVCELEarTFEIQKQDsEIHAAKWMPVEEYVNQPYH 242
Cdd:cd18874  81 VFvdYLARTD--SSEVVLNE-EAVEYLWVEPEEALKYPLN 117

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        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79552110 125 IGIGAFVL--NKNGEMLVVQENSGYFKDKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFM---ES---HQ 196
Cdd:cd04694   1 VDVGVVVLieDSDDRVLLTRRAKHMRTFPGVWVPPGGHVELGESLLEAGLRELQEETGLEVSDIQSLSLLglwESvypTL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 79552110 197 AVWQRKTD----IFFVC---ELEARTFEIQKQDSEIHAAKWMPVEE 235
Cdd:cd04694  81 LSIGLPKRhhivVYYLVklsESHENQEQLKLQEDEVDAAVWLPKSL 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 79552110 125 IGIGAFVLNKNGEMLVVQEnsGYFKDknvWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFMESHQAVWQRKTD 204
Cdd:cd04680   1 LGVRAIVLDDAGRVLLVRH--TYVPG---WYLPGGGVDKGETAEEAARRELREEAGVVLTGPPRLFGVYFNRRVSPRDHV 75

                        90       100
                ....*....|....*....|....*...
gi 79552110 205 IFFVCELEARTfEIQKQDSEIHAAKWMP 232
Cdd:cd04680  76 ALYRVREFEQT-EPPEPNGEIAEAGFFA 102

RNA pyrophosphohydrolase; Reviewed

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 79552110  123 HRIGIGAFVLNKNGEMLVVQEnsgyFKDKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVL 189
Cdd:PRK00714   7 YRPNVGIILLNRQGQVFWGRR----IGQGHSWQFPQGGIDPGETPEQAMYRELYEEVGLRPEDVEIL 69

diadenosine tetraphosphate; Diadenosine tetraphosphate (Ap4A; EC 3.6.1.17), also called NUDIX (nucleoside diphosphate-linked moiety X)) motif 2/Nudt2, is a member of the NUDIX hydrolase superfamily. Ap4A hydrolases are well represented in a variety of prokaryotic and eukaryotic organisms. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one subfamily and fungi/animals/archaea enzymes, represented by this subfamily, fall into another. Bacterial enzymes are found in both subfamilies. Ap4A is a potential by-product of aminoacyl tRNA synthesis, and accumulation of Ap4A has been implicated in a range of biological events, such as DNA replication, cellular differentiation, heat shock, metabolic stress, and apoptosis. Ap4A hydrolase cleaves Ap4A asymmetrically into ATP and AMP. It is important in the invasive properties of bacteria and thus presents a potential target for inhibition of such invasive bacteria. Besides the signature NUDIX motif (G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val) that functions as a metal binding and catalytic site, and a required divalent cation, Ap4A hydrolase is structurally similar to the other members of the NUDIX hydrolase superfamily with some degree of variation. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79552110 133 NKNGEMLVVQENSGYFkdknvWKVPTGTIKEGESIWAGAVREVKEET-----DIDAEFVEVL--SFMESHQavwqrKTDI 205
Cdd:cd03428  14 NGEIEFLLLQHSYGGH-----WDFPKGHVEPGESELETALRETKEETgltvdDLPPGFRETLtySFKEGVE-----KTVV 83

                        90       100       110
                ....*....|....*....|....*....|
gi 79552110 206 FFVCELEaRTFEIqKQDSEIHAAKWMPVEE 235
Cdd:cd03428  84 YFLAELT-PDVEV-KLSEEHQDYKWLPYEE 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 79552110 128 GAFVLN-KNGEMLVVQENsgyfkdK-NVWKVPTGTIKEGESIWAGAVREVKEET---------------DIDAEFVEVLS 190
Cdd:cd03674   5 SAFVVNpDRGKVLLVHHR------KlGRWLQPGGHVEPDEDPLEAALREAREETgldvellsplspdplDIDVHPIPANP 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 79552110 191 FMESHQavwqrKTDIFFVCELEARtfEIQKQDSEIHAAKWMPVEE 235
Cdd:cd03674  79 GEPAHL-----HLDVRYLAVADGD--EALRKSDESSDVRWFPLDE 116

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 79552110 149 KDKNVWKVPTGTIKEGESIWAGAVREVKEET--DIDAEFVEVLSFMES-----HqaVWQRKTDiFFVCELEARTFEIQ-- 219
Cdd:cd04662  30 KDEGAWSIPKGEVEPGEDPLAAARREFEEETgfPAPGPFIPLGEVRQKsgkvvH--AWAVEGD-LDPAAIVSNTFELEwp 106

                        90       100
                ....*....|....*....|..
gi 79552110 220 ----KQDS--EIHAAKWMPVEE 235
Cdd:cd04662 107 prsgRRQEfpEVDRAAWFPLEE 128

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 79552110 130 FVLNKNGEMLVvQENSgyfKDKNVWkvP-------TGTIKEGESIWAGAVREVKEETDIDAefVEVLSFMESHQAVWQRK 202
Cdd:COG1443  35 FVFNSDGRLLL-QRRA---LTKDHW--PglwdntvCGHPRAGETYEEAAVRELEEELGITV--DDDLRPLGTFRYRAVDA 106

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 79552110 203 TDIF-------FVCELEArtfEIQKQDSEIHAAKWMPVEE 235
Cdd:COG1443 107 NGLVenefchvFVARLDG---PLTPQPEEVAEVRWVTLEE 143

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 79552110 134 KNGEMLVVQENSGyfkdknVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSFMESHQ----AVWQRKTDIFFVC 209
Cdd:cd18889  11 KDDKILLVQEKDG------RWSLPGGWVDVNQSIKENTIKEAKEEAGLDVEPKRIIAVLDRNKhnkpPYAYGIYKIFVLC 84

                        90       100
                ....*....|....*....|....*.
gi 79552110 210 ELEARTFEiqkQDSEIHAAKWMPVEE 235
Cdd:cd18889  85 ELLGGEFQ---PNIETIESGYFSLDE 107

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 79552110 127 IGAF-VLNKNGEMLVVQENSGYFKdkNVWKVPTGTIKEGESIWAGAVREVKEETDidaefVEVLSFME----SHQAVWQR 201
Cdd:cd04686   2 FGVYgIIIRNDKLLLIRKTRGPYQ--GRYDLPGGSQEFGESLEDALKREFAEETG-----MTVTSYDNlgvyDFFVPWSD 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 79552110 202 KTD-----IFFVCELEARTFEI------QKQDSEIHAakWMPVEE 235
Cdd:cd04686  75 KELgdvhhIGVFYDVELLDNNIsellqfEGQDSLGAV--WIPLQD 117

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79552110 129 AFVLNKNGEMLVVQEnsgyfKDKNVWKVPTGTIKEGESIWAGAVREVKEE--TDIDAefvEVLSFMESHQAVWQRKTDIf 206
Cdd:cd04690   5 AVIIIKDGRLLLVRK-----RGTDAFYLPGGKREPGETPLQALVRELKEElgLDLDP---DSLRFLGTFEAPAANEPGT- 75

                        90       100       110
                ....*....|....*....|....*....|....*
gi 79552110 207 fvcELEARTFEIQ-----KQDSEIHAAKWMPVEEY 236
Cdd:cd04690  76 ---TVRMTCFTADydgepQPAAEIEELRWLDPADP 107

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 79552110 159 GTIKEGESIWAGAVREVKEETDIDA---EFVEVLSFmESHQAVWQRKTDIFFvceleARTFEIQKQDSEIHAAKWMPVEE 235
Cdd:cd03427  34 GKVEPGETIEEAAVRELEEEAGLTAtelEKVGRLKF-EFPDDPEAMDVHVFR-----ADSWTGEPQETEEMRPQWFDLDD 107

                ....*..
gi 79552110 236 YvnqPYH 242
Cdd:cd03427 108 I---PYD 111

NADH pyrophosphatase; NADH pyrophosphatase, also known as NUDIX (nucleoside diphosphate linked moiety X)) motif 13/Nudt13, is thought to have NADH pyrophosphatase activity, be involved in NADH metabolic process and NADP catabolic process, catalyzing the cleavage of NADH into reduced nicotinamide mononucleotide (NMNH) and AMP, and located in mitochondrion. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity. Members of this family are also recognized by 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. A block of 8 conserved amino acids downstream of the NUDIX motif is thought to give NADH pyrophosphatase its specificity for NADH. NADH pyrophosphatase forms a dimer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79552110 131 VLNKNGEMLVVQeNSGYfkDKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVE-VLSfmeshQAvWQRKTDIFFVC 209
Cdd:cd03429   8 VTNGEDKILLAR-QPRW--PPGRYSLLAGFVEPGETLEEAVRREVKEEVGLRVKNVRyVGS-----QP-WPFPSSLMLGF 78

                        90       100
                ....*....|....*....|....*..
gi 79552110 210 ELEARTFEIQKQDSEIHAAKWMPVEEY 236
Cdd:cd03429  79 TAEADSGEITVDDDELEDARWFSRDEL 105

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79552110 133 NKNGEMLVVQENSGYFKDKnvWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVL-SFMESHQAVWQRKTDIFFVCEL 211
Cdd:cd18873  14 DGELKVLLIKRKNEPFKGG--WALPGGFVREDETLEDAARRELREETGLKDIYLEQLgTFGDPDRDPRGRVISVAYLALV 91

                        90       100
                ....*....|....*....|....
gi 79552110 212 EARTFEIQKQDsEIHAAKWMPVEE 235
Cdd:cd18873  92 PEEDLAPKAGD-DAAEARWFPVDE 114

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.

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gi 79552110 124 RIGIGAFVLNKNGEMLVVQEnsgyfKDKNVWKVPTGTIKEGESIWAGAVREVKEETDIDAEFVEVLSF----MESH--QA 197
Cdd:cd18890   2 KVDIRAVVFNDKEEILLVKE-----KEDGKWTLPGGWADVGYTPTEVAAKEVEEETGLEVSPKKLLAIldkrKHPHppQP 76