NCBI Conserved Domain Search

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.

Pssm-ID: 467543 [Multi-domain] Cd Length: 138 Bit Score: 209.30 E-value: 8.27e-71

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   6 VTVACVVHAEGKFLVVEETINGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPD-KTPFLRFLF 84
Cdd:cd03675    1 VTVAAVVERDGRFLLVEEETDGRLVLNQPAGHLEPGESLLEAAIRETLEETGWEVEPTALLGIYQWTAPDnGVTYLRFAF 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 446398238  85 AIELEQICPTQPHDSDIDCCRWVSAEEIL-QASNLRSPLVAESIRCYQSGQRYPLEMI 141
Cdd:cd03675   81 AGELLEHLPDQPLDSGIIRAHWLTLEEILaLQARLRSPLVLRCIEDYLAGQRYPLSLI 138

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 89.27 E-value: 1.03e-23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   1 MFKPHVTVACVV-HAEGKFLVVEETI-NGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWiaPDKTP 78
Cdd:COG1051    2 TKVPKVAVDAVIfRKDGRVLLVRRADePGKGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDH--PDRGH 79

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 446398238  79 FLRFLFAIELEQICPTQphDSDIDCCRWVSAEEILQ 114
Cdd:COG1051   80 VVSVAFLAEVLSGEPRA--DDEIDEARWFPLDELPE 113

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.

Pssm-ID: 467528 [Multi-domain] Cd Length: 106 Bit Score: 79.76 E-value: 3.12e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   5 HVTVACVVHAEGKFLVVEETIN-GKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPD-KTPFLRF 82
Cdd:cd02883    1 VAVGAVVFDDEGRVLLVRRSDGpGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDeGRHVVVL 80

                         90       100
                 ....*....|....*....|....*.
gi 446398238  83 LFAIELEQICPTQPHDSDIDCCRWVS 108
Cdd:cd02883   81 VFLARVVGGEPPPLDDEEISEVRWVP 106

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.

Pssm-ID: 467554 [Multi-domain] Cd Length: 131 Bit Score: 77.58 E-value: 3.82e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   9 ACVVHAEGKFLVVEETINGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRM-----HQWIAPDktpfLRFL 83
Cdd:cd04670    7 GLVINENNEVLVVQEKYGGPGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFrhqhpGRFGKSD----LYFV 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 446398238  84 FAIELE-----QICPtqphdSDIDCCRWVSAEEILQASN--LRSPLVAESIRCY 130
Cdd:cd04670   83 CRLRPLsdeeiKICP-----EEIAEAKWMPLEEYLKQPNvsQINKLVAKLLLEC 131

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 75.60 E-value: 3.42e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238    3 KPHVTVACVVH-AEGKFLVVEETIN-GKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKTPFL 80
Cdd:pfam00293   1 KRRVAVGVVLLnEKGRVLLVRRSKKpFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRFP 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 446398238   81 R-----FLFAIELEQIcPTQPHDSDIDCCRWVSAEEIL 113
Cdd:pfam00293  81 DeheilYVFLAEVEGE-LEPDPDGEVEEVRWVPLEELL 117

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

Pssm-ID: 440260 [Multi-domain] Cd Length: 143 Bit Score: 73.14 E-value: 2.91e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   4 PHVTVACVVHAEGKFLVVEET--INGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIrmHQWIAPDKTPFLR 81
Cdd:COG0494   13 RPAVVVVLLDDDGRVLLVRRYryGVGPGLWEFPGGKIEPGESPEEAALRELREETGLTAEDLELL--GELPSPGYTDEKV 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 446398238  82 FLFAIE-LEQICPTQPHDSD-IDCCRWVSAEEILQAsnLRSPLVAESIR 128
Cdd:COG0494   91 HVFLARgLGPGEEVGLDDEDeFIEVRWVPLDEALAL--VTAGEIAKTLA 137

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.

Pssm-ID: 467573 [Multi-domain] Cd Length: 122 Bit Score: 69.25 E-value: 7.05e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   6 VTVACVVHAEGKFLVVEETING-KALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDK--TPFLRF 82
Cdd:cd04691    2 LGVGGVVVKEGKVLLVKRAYGPgKGRWTLPGGFVEEGETLDEAIVREVLEETGIDAKPVGIIGVRSGVIRDGksDNYVVF 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 446398238  83 LfaieLEQICPTQPHDS-DIDCCRWVSAEEILQasnlrSPLVAESIR 128
Cdd:cd04691   82 L----LEYVGGEPKPDErENSEAGFLTLEEALA-----NEDIADMSR 119

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.

Pssm-ID: 467557 [Multi-domain] Cd Length: 128 Bit Score: 66.77 E-value: 5.40e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   6 VTVACVVHAEGKFLVVEEtinGKA----LWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKTPFLR 81
Cdd:cd04673    2 VAVGAVVFRDGRVLLVRR---GNPpdagLWSFPGGKVELGETLEDAALRELREETGLEAEVVGLLTVVDVIERDEAGRVR 78

                         90       100       110
                 ....*....|....*....|....*....|
gi 446398238  82 FLFAIeleqicptqphdsdID-CCRWVSAE 110
Cdd:cd04673   79 FHYVI--------------LDfLAEWVSGE 94

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.

Pssm-ID: 467542 [Multi-domain] Cd Length: 130 Bit Score: 63.05 E-value: 1.54e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   5 HVTVACVV--HAEGKFLVVEETINGKalWNQPAGHLEADETLVEAAARELWEETGISAQP------------QHFIRMHQ 70
Cdd:cd03674    1 HFTASAFVvnPDRGKVLLVHHRKLGR--WLQPGGHVEPDEDPLEAALREAREETGLDVELlsplspdpldidVHPIPANP 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 446398238  71 WIAP----DktpfLRFLFAIELEQicptQPHDSD-IDCCRWVSAEEILQASNLR 119
Cdd:cd03674   79 GEPAhlhlD----VRYLAVADGDE----ALRKSDeSSDVRWFPLDELEELSMDP 124

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

Pssm-ID: 467552 [Multi-domain] Cd Length: 117 Bit Score: 62.69 E-value: 1.90e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  10 CVVHAEGKFLVVEETingKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQwiAPDKtpfLRFLFAIELE 89
Cdd:cd04667    5 VICRRGDRILLVARR---GGRWLLPGGKIEPGESPLEAAIRELKEETGLAALSLLYLFEHE--GPHK---LHHVFLAEAP 76

                         90       100
                 ....*....|....*....|
gi 446398238  90 QICPTQPHDsDIDCCRWVSA 109
Cdd:cd04667   77 DGGRPRPGN-EIARCRWVSA 95

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

Pssm-ID: 467549 [Multi-domain] Cd Length: 132 Bit Score: 59.96 E-value: 3.30e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   6 VTVACVVH---AEGKFLVVEETINGKAlWNQPAGHLEADETLVEAAARELWEETGISAQP--------QHFIRMHQWIAP 74
Cdd:cd04664    1 FSVLVVIYrkdEEGEVLLLKRTDDGGF-WQSVTGGIEDGETPWQAALRELKEETGLDPLElqlidlnvSNFYEIFDDWRP 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 446398238  75 DKTPFLRFLFAIELEQICP---TQPHdsdiDCCRWVSAEEILQ 114
Cdd:cd04664   80 GVTVNTEHVFAVEVPEEQPirlSPEH----TDYRWLPYEEAAE 118

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.

Pssm-ID: 467591 [Multi-domain] Cd Length: 126 Bit Score: 58.69 E-value: 6.62e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  15 EGKFLVVEETINGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKtPFLR--FLFAIELEQIC 92
Cdd:cd18880   11 DGKLLLVKHRDEGGIFYILPGGGQEHGETLPEALKRECLEETGLDVEVGDLLFVREYIGPNK-PVHQveLFFLCTLEGGE 89

                         90       100
                 ....*....|....*....|....
gi 446398238  93 PTQPHDSDIDC--CRWVSAEEILQ 114
Cdd:cd18880   90 LTLGSDPDLNQvgVEWIPLEELDS 113

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.

Pssm-ID: 467561 [Multi-domain] Cd Length: 128 Bit Score: 57.57 E-value: 2.07e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   4 PHVTVACVV-HAEGKFLVVEET-INGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDK----- 76
Cdd:cd04678    1 PRVGVGVIVlNDDGKVLLGRRKgSHGAGTWALPGGHLEFGESFEECAAREVLEETGLEIRNVRFLTVTNDVFEEEgkhyv 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 446398238  77 TPFLR-FLFAIELEQICPtqPHDsdidcC---RWVSAEEILQASNLRSPLVA 124
Cdd:cd04678   81 TIFVLaEVDDGEPEENME--PDK-----CegwEWFSWDELPPLRPLFLPLAN 125

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.

Pssm-ID: 467572 [Multi-domain] Cd Length: 123 Bit Score: 57.16 E-value: 2.42e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   6 VTVACVVHAEGKFLVVEEtiNGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAP----DKTPFLR 81
Cdd:cd04690    2 VKAAVIIIKDGRLLLVRK--RGTDAFYLPGGKREPGETPLQALVRELKEELGLDLDPDSLRFLGTFEAPaanePGTTVRM 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 446398238  82 FLFAIEL-EQICPtqphDSDIDCCRWVSAEEILQAsnLRSPLVAE 125
Cdd:cd04690   80 TCFTADYdGEPQP----AAEIEELRWLDPADPDDD--RLAPLLRE 118

ADP-ribose pyrophosphatase, UDP-glucose pyrophosphatase, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) ( NUDIX (Nucleoside diphosphate-linked moiety X)) motif 5; Nudt5) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

Pssm-ID: 467530 [Multi-domain] Cd Length: 134 Bit Score: 57.13 E-value: 3.24e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   8 VACV-VHAEGKFLVVEE---TInGKALWNQPAGHLEADETLVEAAARELWEETGISAqpQHFIRMHQwIAPDktP----- 78
Cdd:cd03424    5 VAVLaITDDGKVVLVRQyrhPV-GRVLLELPAGKIDPGEDPEEAARRELEEETGYTA--GDLELLGS-FYPS--Pgfsde 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 446398238  79 FLRFLFAIELEQICPTQPHDSDIDCCRWVSAEEILQA 115
Cdd:cd03424   79 RIHLFLAEDLTPVSEQALDEDEFIEVVLVPLEEALEM 115

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.

Pssm-ID: 467588 [Multi-domain] Cd Length: 121 Bit Score: 56.44 E-value: 4.99e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  14 AEGKFLVVEETinGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFiRMHQWIAPDK--TPFLRFLFA---IEL 88
Cdd:cd18876   10 AAGRVLLVKPT--YKDGWELPGGVVEAGESPLQAARREVREELGLDVPVGRL-LAVDWVPPAGggDDAVLFVFDggvLTP 86

                         90       100
                 ....*....|....*....|....*.
gi 446398238  89 EQICPTQPHDSDIDCCRWVSAEEILQ 114
Cdd:cd18876   87 EQAAAIRLQDEELSAYRFVTPEEAAE 112

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.

Pssm-ID: 467585 [Multi-domain] Cd Length: 132 Bit Score: 56.01 E-value: 9.55e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   4 PHVTVACVVHA----EGKFLVVEETIN-GKALWNQPAGHLEADETLVEAAARELWEETGIsaQPQHFIRMHQWIAPDKTP 78
Cdd:cd18873    1 PSVTVDCVIFGfddgELKVLLIKRKNEpFKGGWALPGGFVREDETLEDAARRELREETGL--KDIYLEQLGTFGDPDRDP 78

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 446398238  79 FLRFL---FAIELEQICPTQPHDSDIDCCRWVSAEEIL 113
Cdd:cd18873   79 RGRVIsvaYLALVPEEDLAPKAGDDAAEARWFPVDELL 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.

Pssm-ID: 467564 [Multi-domain] Cd Length: 135 Bit Score: 56.04 E-value: 1.02e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   8 VACVVHAEGKFLVVEETIN-GKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMhqwiAPDKTPFLRFL--- 83
Cdd:cd04681    9 VGVIIRNEGEILFVRRAKEpGKGKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYLCS----LPNTYLYKGITykt 84

                         90       100       110
                 ....*....|....*....|....*....|...
gi 446398238  84 ----FAIELEQICPTQPHDSDIDCCRWVSAEEI 112
Cdd:cd04681   85 cdlfFTAELDEKPKLKKAEDEVAELEWLDLEEI 117

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.

Pssm-ID: 467596 [Multi-domain] Cd Length: 147 Bit Score: 56.09 E-value: 1.14e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  10 CVVHAEGKFLVVEETI-NGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKTPF-LRFLFAIE 87
Cdd:cd18886    5 CFIIRDDEVLLLNRNKkPNMGKWNGVGGKLEPGESPEECAIREVFEETGLELEDLQLRGIVTFPSFDGGEDwLMYVFLAE 84

                         90       100       110
                 ....*....|....*....|....*....|..
gi 446398238  88 LeqicptqPHDSDIDCCR-----WVSAEEILQ 114
Cdd:cd18886   85 A-------FSGELVESDRegilaWVPIDWLLN 109

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.

Pssm-ID: 467579 [Multi-domain] Cd Length: 118 Bit Score: 55.32 E-value: 1.15e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 446398238   5 HVTVACVVHAEGKFLVVEETINGKALWNQPAGHLEADETLVEAAARELWEETGISAQP 62
Cdd:cd04699    2 PVSVKGVIFDNGRVLLLRRSRAGAGEWELPGGRLEPGESPEEALKREVKEETGLDVSV 59

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.

Pssm-ID: 467545 [Multi-domain] Cd Length: 123 Bit Score: 55.28 E-value: 1.38e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 446398238   4 PHVTVACVVHAEGKFLVVEETING-KALWNQPAGHLEADETLVEAAARELWEETGISAQPQH 64
Cdd:cd04511    1 PKIVVGCLPEWEGKVLLCRRAIEPrKGYWTLPAGFMELGETTEQGAARETREEAGARVEIGS 62

RNA pyrophosphohydrolase; The initiation of mRNA degradation often requires deprotection of its 5' end. In eukaryotes, the 5'-methylguanosine (cap) structure is principally removed by the NUDIX family decapping enzyme Dcp2, yielding a 5'-monophosphorylated RNA that is a substrate for 5' exoribonucleases. In bacteria, the 5'-triphosphate group of primary transcripts is also converted to a 5' monophosphate by a NUDIX protein called RNA pyrophosphohydrolase (RppH), allowing access to both endo- and 5' exoribonucleases. 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.

Pssm-ID: 467550 [Multi-domain] Cd Length: 121 Bit Score: 54.95 E-value: 1.71e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   8 VACVVHAEGKFLVVE-ETINGkalWNQPAGHLEADETLVEAAARELWEETGisAQPQHFIRMHQWIAPDKT-PFLRFLFA 85
Cdd:cd04665    3 VVVIARYKGKWLFTRhKERRG---WEFPGGKREPGETIEEAARRELYEETG--AVIFELKPLGQYSVHGKGqEFFGAVYY 77

                         90
                 ....*....|..
gi 446398238  86 IELEQICPTQPH 97
Cdd:cd04665   78 AEVKSFEPILPY 89

diadenosine hexaphosphate (Ap6A) hydrolase; Diadenosine hexaphosphate (Ap6A) hydrolase is a member of the NUDIX hydrolase superfamily. Ap6A hydrolase specifically hydrolyzes diadenosine polyphosphates, but not ATP or diadenosine triphosphate, and it generates ATP as the product. Ap6A, the most preferred substrate, hydrolyzes to produce two ATP molecules, which is a novel hydrolysis mode for Ap6A. These results indicate that Ap6A hydrolase is a diadenosine polyphosphate hydrolase. It requires the presence of a divalent cation, such as Mn2+, Mg2+, Zn2+, and Co2+, for activity. Members of the NUDIX hydrolase superfamily are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site.

Pssm-ID: 467541 [Multi-domain] Cd Length: 131 Bit Score: 55.25 E-value: 1.84e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  14 AEGKFLVVEEtiNGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFI-RMHQWIAPDKTPFLR--FLFAIELEQ 90
Cdd:cd03673   14 GGGEVLLIHR--PRYDDWSLPKGKLEPGETPEEAAVREVEEETGLRVRLGRPLgTTRYTYTRKGKGILKkvHYWLMRALG 91

                         90       100
                 ....*....|....*....|....*
gi 446398238  91 ICPTQPHDSDIDCCRWVSAEEILQA 115
Cdd:cd03673   92 GEFLPQPEEEIDEVRWLPPDEARRL 116

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.

Pssm-ID: 467533 [Multi-domain] Cd Length: 136 Bit Score: 55.23 E-value: 1.86e-10

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 446398238  27 GKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFI 66
Cdd:cd03427   25 GAGKWNGFGGKVEPGETIEEAAVRELEEEAGLTATELEKV 64

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.

Pssm-ID: 467555 [Multi-domain] Cd Length: 130 Bit Score: 53.08 E-value: 1.26e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   5 HVTVACVVHAEGKFLVVEE---TINGKalWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIrMHQWIAPDktpFLR 81
Cdd:cd04671    1 YVVAAVIINEQGEVLMIQEakrSCRGK--WYLPAGRVEPGESIVEAAKREVKEETGLKCEPSTLL-SVEEAGGS---WYR 74


                 ...
gi 446398238  82 FLF 84
Cdd:cd04671   75 FVF 77

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.

Pssm-ID: 467587 [Multi-domain] Cd Length: 144 Bit Score: 52.96 E-value: 1.54e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 446398238   7 TVACVVH-AEGKFLVVEETINGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKTPFLRFLF 84
Cdd:cd18875    4 TNMCMIYdGEDRVLVLDRVKKDWGGYTFPGGHVEPGESFVDSVIREVKEETGLTIKNPELCGIKQWINPDGERYIVFLY 82

plant diadenosine tetraphosphate (Ap4A) hydrolase and similar proteins; Diadenosine tetraphosphate (Ap4A) hydrolase is a member of the NUDIX hydrolase superfamily. Members of this family are well represented in a variety of prokaryotic and eukaryotic organisms. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one group (represented by this subfamily) and fungi/animals/archaea enzymes 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 the inhibition of such invasive bacteria. Besides the signature NUDIX motif (G[X5]E[X7]REUXEEXGU where U is Ile, Leu, or Val), Ap4A hydrolase is structurally similar to the other members of the NUDIX hydrolase superfamily with some degree of variations. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies.

Pssm-ID: 467539 [Multi-domain] Cd Length: 147 Bit Score: 52.57 E-value: 2.07e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 446398238   9 ACVVHAEGKFLVVEEtINGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFI-RMHQWIAPD 75
Cdd:cd03671    8 IVLFNRDGQVLVGRR-IDVPGAWQFPQGGIDEGEDPEEAALRELYEETGLSPEDVEIIaETPDWLTYD 74

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.

Pssm-ID: 467593 [Multi-domain] Cd Length: 130 Bit Score: 51.10 E-value: 6.22e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  31 WNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKTpfLRFLFAIELEqiCPTqphdSDIDCC-----R 105
Cdd:cd18882   32 WGLFGGHLEPGETPEEAIRRELEEEIGYEPGEFRFFLLYTEDDGEDR--IRHVFHAPLD--VDL----SDLVLNegqalR 103


                 ....*....
gi 446398238 106 WVSAEEILQ 114
Cdd:cd18882  104 LFSPEEILQ 112

DR1025 and similar proteins; DR1025 from Deinococcus radiodurans, a member of the NUDIX hydrolase superfamily, show nucleoside triphosphatase and dinucleoside polyphosphate pyrophosphatase activities. Like other enzymes belonging to this superfamily, it requires a divalent cation, in this case Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. In general, 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.

Pssm-ID: 467580 [Multi-domain] Cd Length: 147 Bit Score: 50.68 E-value: 1.50e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  19 LVVEETING----KALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKTPFLRFLFAIELEQ---I 91
Cdd:cd04700   29 LVQEKGISGhpekAGLWHIPSGAVEDGENPQDAAVREACEETGLRVRLVKFLGAYLGRFPDGVLVLRHVWLAEPEPgqvL 108

                         90       100       110
                 ....*....|....*....|....*....|.
gi 446398238  92 CPTQPHdsDIDCCRWVSAEEILQ---ASNLR 119
Cdd:cd04700  109 APAFTD--EIAEASFVSREEFAQlyaAGQIR 137

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.

Pssm-ID: 467566 [Multi-domain] Cd Length: 137 Bit Score: 49.91 E-value: 1.72e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 446398238  30 LWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMH 69
Cdd:cd04683   27 WWHLPAGHVEAGETVRAAAVREAKEELGVEIDPEDLRLVH 66

NUDIX family Ndx2; NUDIX family protein Ndx2 found in Thermus thermophilus has ADP-ribose pyrophosphatase (ADPRase) as well as flavin adenine dinucleotide (FAD) activity. 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.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.

Pssm-ID: 467609 [Multi-domain] Cd Length: 137 Bit Score: 49.09 E-value: 3.64e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   2 FKPHVTVACVVHAEGKFLVVEE---TINGKaLWNQPAGHLEADETLVEAAARELWEETGISAqpQHFIR-MHQWIAPDKT 77
Cdd:cd24161    1 EKNDAVGVLPITDDGEVVLVEQyryPLGGW-SWEIPAGGWPEGEDPEEAARRELREETGLRA--ERWTPlGRFYPSNGVS 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 446398238  78 -----PFLrflfAIELEQiCPTQPHDSDIDC-CRWVSAEEILQ 114
Cdd:cd24161   78 derahVFL----ATGLTP-GEPAPEETEEDLeVRRVPLAEALA 115

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

Pssm-ID: 182536 [Multi-domain] Cd Length: 135 Bit Score: 49.35 E-value: 3.79e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 446398238   8 VACVVHAEGKFLVVEETINGK--ALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQW 71
Cdd:PRK10546   7 VAAIIERDGKILLAQRPAHSDqaGLWEFAGGKVEPGESQPQALIRELREELGIEATVGEYVASHQR 72

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

Pssm-ID: 441052 [Multi-domain] Cd Length: 162 Bit Score: 49.04 E-value: 6.76e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  35 AGHLEADETLVEAAARELWEETGISAQPQ-HFIRMHQWIAPDKTPF----LRFLFAIELEQicPTQPHDSDIDCCRWVSA 109
Cdd:COG1443   64 CGHPRAGETYEEAAVRELEEELGITVDDDlRPLGTFRYRAVDANGLveneFCHVFVARLDG--PLTPQPEEVAEVRWVTL 141


                 ....*.
gi 446398238 110 EEILQA 115
Cdd:COG1443  142 EELLAL 147

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.

Pssm-ID: 467559 [Multi-domain] Cd Length: 144 Bit Score: 48.17 E-value: 9.27e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 446398238   1 MFKPHVTvACVVHAEGKFLVVEETinGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFI 66
Cdd:cd04676   15 LFTPSVA-AVILNEDGRILLQRKG--GLGLWSLPAGAIEPGEHPAEAVIREVREETGLLVKPTRLL 77

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.

Pssm-ID: 467574 [Multi-domain] Cd Length: 142 Bit Score: 47.94 E-value: 1.16e-07

                         10        20        30
                 ....*....|....*....|....*....|...
gi 446398238  35 AGHLEADETLVEAAARELWEETGISAQPQHFIR 67
Cdd:cd04692   62 AGHIDAGETYEEAAVRELEEELGLTVSPEDLIF 94

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.

Pssm-ID: 467535 [Multi-domain] Cd Length: 126 Bit Score: 47.48 E-value: 1.34e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  11 VVHAEGKFLVVEETINGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWiapdktPF-----LRFLFA 85
Cdd:cd03429    8 VTNGEDKILLARQPRWPPGRYSLLAGFVEPGETLEEAVRREVKEEVGLRVKNVRYVGSQPW------PFpsslmLGFTAE 81

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 446398238  86 IELEQICptqPHDSDIDCCRWVSAEEILQASNLRSP 121
Cdd:cd03429   82 ADSGEIT---VDDDELEDARWFSRDELPEALFLPPP 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.

Pssm-ID: 467586 [Multi-domain] Cd Length: 125 Bit Score: 47.28 E-value: 1.81e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   4 PHVTV-ACVVHAEGKFLVVEETiNGKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKtpFLRF 82
Cdd:cd18874    1 PEPTVgALIFNPDGKVLLVRSH-KWNDLYGIPGGKVEWGETLEEALKREVKEETGLDITDIRFILVQESINSEE--FHKP 77

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 446398238  83 LFAIELEQICPTQPHD----SDIDCCRWVSAEEILQ 114
Cdd:cd18874   78 AHFVFVDYLARTDSSEvvlnEEAVEYLWVEPEEALK 113

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.

Pssm-ID: 467534 [Multi-domain] Cd Length: 132 Bit Score: 47.16 E-value: 1.96e-07

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 446398238  17 KFLVVEETINGKalWNQPAGHLEADETLVEAAARELWEETGISA 60
Cdd:cd03428   18 EFLLLQHSYGGH--WDFPKGHVEPGESELETALRETKEETGLTV 59

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.

Pssm-ID: 467575 [Multi-domain] Cd Length: 157 Bit Score: 47.52 E-value: 2.27e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   5 HVTV-ACVVHAEGKFLVVEETINGKA---LWNQ-PAGHLEADETLVEAAARELWEETGIS-----AQPQHFIRMHQWIAp 74
Cdd:cd04693   29 HLVVhVWIFNSDGEILIQQRSPDKKGfpgMWEAsTGGSVLAGETSLEAAIRELKEELGIDldadeLRPILTIRFDNGFD- 107

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 446398238  75 DktpFLRFLFAIELEQIcptQPHDSDIDCCRWVSAEEILQ 114
Cdd:cd04693  108 D---IYLFRKDVDIEDL---TLQKEEVQDVKWVTLEEILE 141

dihydroneopterin triphosphate pyrophosphatase; Provisional

Pssm-ID: 236516 [Multi-domain] Cd Length: 148 Bit Score: 47.20 E-value: 2.38e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 446398238  19 LVVEETINGKAL----------WNQPAGHLEADETLVEAAARELWEETGISAQPQHF 65
Cdd:PRK09438  11 LVVIYTPDLGVLmlqraddpdfWQSVTGSLEEGETPAQTAIREVKEETGIDVLAEQL 67

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 47.95 E-value: 3.36e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   5 HVTVACVVHAEGKFLVVEETiNGK---ALWNQPAGHLEADETLVEAAARELWEETGIS---AQPqHFIRMHQWiaPDKTP 78
Cdd:PRK08999   6 HVAAGVIRDADGRILLARRP-EGKhqgGLWEFPGGKVEPGETVEQALARELQEELGIEvtaARP-LITVRHDY--PDKRV 81


                 ....
gi 446398238  79 FLRF 82
Cdd:PRK08999  82 RLDV 85

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.

Pssm-ID: 467558 [Multi-domain] Cd Length: 118 Bit Score: 45.92 E-value: 4.10e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   6 VTVAcVVHAEGKFLVVEETIN-GKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKTpFLRFLF 84
Cdd:cd04674    6 VVVA-LLPVRDGLLVIRRGIEpGHGELALPGGYIEYGETWQEAAVRELREETGVEADAAEVRLFAVRSAPDGT-LLIFGL 83

                         90
                 ....*....|....*.
gi 446398238  85 AIEL--EQICPTQPHD 98
Cdd:cd04674   84 LPERpvADLPPFAPTD 99

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 47.70 E-value: 4.74e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 446398238   6 VTVACVVHAEGKFLVVE-ETINGKALWNQPAGHLEADETLVEAAARELWEETGI 58
Cdd:PRK05379 204 VTVDAVVVQSGHVLLVRrRAEPGKGLWALPGGFLEQDETLLDACLRELREETGL 257

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.

Pssm-ID: 467568 [Multi-domain] Cd Length: 138 Bit Score: 46.03 E-value: 5.63e-07

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 446398238  27 GKALWNQPAGHLEADETLVEAAARELWEETGISAQP 62
Cdd:cd04685   26 GRSWWFTPGGGVEPGESPEQAAVRELREETGLRLEP 61

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.

Pssm-ID: 467560 [Multi-domain] Cd Length: 137 Bit Score: 45.97 E-value: 6.53e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 446398238   8 VACVVHAEGKFLVVEETINGkaLWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRM 68
Cdd:cd04677   16 AVIILNEQGRILLQKRTDTG--DWGLPGGAMELGESLEETARREVFEETGLTVEELELLGV 74

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.

Pssm-ID: 467531 [Multi-domain] Cd Length: 123 Bit Score: 45.52 E-value: 7.05e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   5 HVTVAcVVHAEGKFLVVEETiNGKAL---WNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKTPFLR 81
Cdd:cd03425    2 EVVAA-IIVDDGRVLIAQRP-EGKHLaglWEFPGGKVEPGETPEQALVRELREELGIEVEVGEPLGTVEHDYPDFHVRLH 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 446398238  82 FLFAIELEQICPTQPHDSdidcCRWVSAEEILQ 114
Cdd:cd03425   80 VYLCTLWSGEPQLLEHQE----LRWVTPEELDD 108

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.

Pssm-ID: 467567 [Multi-domain] Cd Length: 140 Bit Score: 45.31 E-value: 9.66e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   9 ACVVHAEGKFLVVEETINGKALwnqPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQ--WIAPDK-TPFL---RF 82
Cdd:cd04684   20 AVIFNDEGKVLLVQTPNGGYFL---PGGGIEPGETPEEALHREVLEETGWEIEIGEFLGNASryFYSPDYdRYYLnigYF 96

                         90       100       110
                 ....*....|....*....|....*....|....
gi 446398238  83 LFAIELEQIC-PTQP-HDsdidcCRWVSAEEILQ 114
Cdd:cd04684   97 YLAELVRKVSePTEEdHE-----LVWLPPEEAAD 125

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.

Pssm-ID: 467590 [Multi-domain] Cd Length: 142 Bit Score: 44.88 E-value: 1.83e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   4 PHVTvACVVHAEGKFLVVEETINGKalWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQwIAP------DKT 77
Cdd:cd18879   19 PGVT-AVVLRDAGRVLLVRRADNGR--WTPVTGIVEPGEQPADAAVREVLEETGVDVEVERLASVGA-SPPvtypngDQC 94

                         90       100       110
                 ....*....|....*....|....*....|....
gi 446398238  78 PFLRFLFAieleqicptqphdsdidcCRWVSAEE 111
Cdd:cd18879   95 QYLDLTFR------------------CRPVGGEA 110

CDP-Choline Pyrophosphatase and similar proteins; Members include: CDP-Choline Pyrophosphatase, ADP-ribose pyrophosphatase, and UDP-X diphosphatase. CDP-choline pyrophosphatase catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. ADP-ribose pyrophosphatase catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. UDP-X diphosphatase hydrolyzes UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-alanine. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467556 [Multi-domain] Cd Length: 128 Bit Score: 44.47 E-value: 1.97e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 446398238   4 PHVTVACVVHAEGKFLVVEETINGkaLWNQPAGHLEADETLVEAAARELWEETGISAQPQHFI 66
Cdd:cd04672    1 PKVDVRAAVFKDGKILLVREKSDG--RWTLPGGWADVGLSPAENAVKEVREESGYEVRARKLL 61

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.

Pssm-ID: 467576 [Multi-domain] Cd Length: 135 Bit Score: 43.44 E-value: 5.64e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 446398238   7 TVACVVHAEGKFLVVEETINGKA---LWNQPAGHLEADETLVEAAARELWEETGI 58
Cdd:cd04694    5 VVVLIEDSDDRVLLTRRAKHMRTfpgVWVPPGGHVELGESLLEAGLRELQEETGL 59

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.

Pssm-ID: 467553 [Multi-domain] Cd Length: 120 Bit Score: 42.73 E-value: 6.16e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 446398238  11 VVHAEGKFLVVEETINGKALWNQPAGHLEADETLVEAAARELWEETGISAQ 61
Cdd:cd04669    6 VIYDDDKLLLIRRTKPGEEYYVFPGGGIEPGETPEEAALREAVEELGLDVA 56

ADP-ribose pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase) (also known as NUDIX (Nucleoside diphosphate-linked moiety X)) motif 5; Nudt5) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity.

Pssm-ID: 467598 [Multi-domain] Cd Length: 149 Bit Score: 43.24 E-value: 7.11e-06

                         10        20
                 ....*....|....*....|....
gi 446398238  34 PAGHLEADETLVEAAARELWEETG 57
Cdd:cd18888   38 PAGLVDPGESPEQAALRELKEETG 61

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.

Pssm-ID: 467563 [Multi-domain] Cd Length: 121 Bit Score: 42.62 E-value: 8.89e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 446398238   9 ACVVHAEGKFLVVEET-INGkalWNQPAGHLEADETLVEAAARELWEETGISA 60
Cdd:cd04680    5 AIVLDDAGRVLLVRHTyVPG---WYLPGGGVDKGETAEEAARRELREEAGVVL 54

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.

Pssm-ID: 467578 [Multi-domain] Cd Length: 157 Bit Score: 42.99 E-value: 9.18e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  11 VVHAEGKFLVVEETINgKALWnqpAGHL--------EADETLVEAAARELWEETGISAQPQHFI--------RMHQWIAp 74
Cdd:cd04697   33 VRNAAGRLLVQKRTMD-KDYC---PGYLdpatggvvGAGESYEENARRELEEELGIDGVPLRPLftfyyeddRSRVWGA- 107

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 446398238  75 dktpflrfLFAIELEQicPTQPHDSDIDCCRWVSAEEILQASN 117
Cdd:cd04697  108 --------LFECVYDG--PLKLQPEEVAEVDWMSEDEILQAAR 140

RNA pyrophosphohydrolase; Reviewed

Pssm-ID: 234820 [Multi-domain] Cd Length: 156 Bit Score: 42.45 E-value: 1.33e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  31 WNQPAGHLEADETLVEAAARELWEETGISAQ----------------PQHFIRMHQ---------WIApdktpfLRFLFa 85
Cdd:PRK00714  34 WQFPQGGIDPGETPEQAMYRELYEEVGLRPEdveilaetrdwlrydlPKRLVRRSKgvyrgqkqkWFL------LRLTG- 106

                         90       100
                 ....*....|....*....|....*...
gi 446398238  86 iELEQICPTQPHDSDIDCCRWVSAEEIL 113
Cdd:PRK00714 107 -DDSEINLNTTSHPEFDAWRWVSYWYPL 133

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.

Pssm-ID: 467548 [Multi-domain] Cd Length: 132 Bit Score: 41.13 E-value: 3.44e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 446398238   8 VACVV--HAEGKFLVVEETINGKALWNQPAGHLEADETLVEAAARELWEETGISAQP 62
Cdd:cd04663    3 VCAYVtrGRNRELLVFEHPDFPEAGLQVPKGTVEPGESPEEAALRELAEETGLTGAR 59

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.

Pssm-ID: 467569 [Multi-domain] Cd Length: 130 Bit Score: 40.74 E-value: 4.02e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   5 HVTVACVVHAEGKFLVVEETING-KALWNQPAGHLEADETLVEAAARELWEETGIS----AQPQHFIRMHQWIAPDKTPF 79
Cdd:cd04686    1 HFGVYGIIIRNDKLLLIRKTRGPyQGRYDLPGGSQEFGESLEDALKREFAEETGMTvtsyDNLGVYDFFVPWSDKELGDV 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 446398238  80 --LRFLFAIELE-QICPTQPHDSDIDCC--RWVSAEEIlqASNLRSPLV 123
Cdd:cd04686   81 hhIGVFYDVELLdNNISELLQFEGQDSLgaVWIPLQDL--TELNSSPLV 127

diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 and similar proteins; Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 (DIPP2), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 4; Nudt4, and other proteins including DIPP1/Nudt3, DIPP3a;APS2/Nudt10 and DIPP3beta;APS1/Nudt11. DIPP regulates the turnover of diphosphoinositol polyphosphates. The turnover of these high-energy diphosphoinositol polyphosphates represents a molecular switching activity with important regulatory consequences. Molecular switching by diphosphoinositol polyphosphates may contribute to regulating intracellular trafficking. Several alternatively spliced transcript variants have been described, but the full-length nature of some variants has not been determined. Isoforms DIPP2alpha and DIPP2beta are distinguishable from each other solely by DIPP2beta possessing one additional amino acid due to intron boundary skidding in alternate splicing. 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.

Pssm-ID: 467551 [Multi-domain] Cd Length: 128 Bit Score: 40.59 E-value: 4.69e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  34 PAGHLEADETLVEAAARELWEETGI--SAQPQHFIRMH--QWIAPDKTPFLRFLFAIELEQICPTQPhDSDIDCCRWVSA 109
Cdd:cd04666   31 PKGGPEKGETPAEAAAREAWEEAGVrgKVLKRPLGVYRyrKRLKGRGLPCRVHVFPLEVTEELDDWP-EKHERKRRWFSP 109


                 ..
gi 446398238 110 EE 111
Cdd:cd04666  110 EE 111

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.

Pssm-ID: 467600 [Multi-domain] Cd Length: 129 Bit Score: 40.48 E-value: 5.32e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 446398238   4 PHVTV-ACVVHAEGKFLVVEETINGKalWNQPAGHLEADETLVEAAARELWEETGISAQPQHFI-----RMHQ 70
Cdd:cd18890    1 PKVDIrAVVFNDKEEILLVKEKEDGK--WTLPGGWADVGYTPTEVAAKEVEEETGLEVSPKKLLaildkRKHP 71

NUDIX domain family NudE found in Escherichia coli, and similar proteins; The adenosine nucleotide hydrolase NudE protein in Escherichia coli is a NUDIX hydrolase family member active against ADP ribose, NADH, AP2A and AP3A33, and is classified as a hydrolase (E.C. 3.6.1.-) based on gene annotations. It is an 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. 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.

Pssm-ID: 467604 [Multi-domain] Cd Length: 134 Bit Score: 39.15 E-value: 1.94e-04

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 446398238  34 PAGHLEADETLVEAAARELWEETGISAQPQHFIRM 68
Cdd:cd24156   34 PKGLIDPGETPEEAANRELKEEIGFGARQLTLLRE 68

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

Pssm-ID: 467532 [Multi-domain] Cd Length: 158 Bit Score: 39.01 E-value: 2.48e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  34 PAGHLEA-DETLVEAAARELWEETGISAQ--------PQHFIRMHQWIAPdktpflrFLFAIELEQicPTQPHDSDIDCC 104
Cdd:cd03426   37 PGGKREPgDESPVETALRETEEEIGLPPEsvevlgrlDPLYTPSGFVVTP-------FVGLLDDPP--PLRPNPDEVAEV 107

                         90       100
                 ....*....|....*....|....*..
gi 446398238 105 RWVSAEEILQASNLRSPLVAESIRCYQ 131
Cdd:cd03426  108 FTVPLSFLLDPEPRRYETFLRSGPRGT 134

nudix hydrolase

Pssm-ID: 215184 [Multi-domain] Cd Length: 144 Bit Score: 38.69 E-value: 2.97e-04

                         10        20        30
                 ....*....|....*....|....*....|....
gi 446398238  26 NGKALWNQPAGHLEADETLVEAAARELWEETGIS 59
Cdd:PLN02325  31 IGDSTFALPGGHLEFGESFEECAAREVKEETGLE 64

ADP-ribose pyrophosphatase from Mycobacterium tuberculosis (Mt-ADPRase), and similar proteins; Mycobacterium tuberculosis ADP-ribose pyrophosphatase mt-ADPRase(also called Rv1700) is a NUDIX protein that catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

Pssm-ID: 467606 [Multi-domain] Cd Length: 174 Bit Score: 38.74 E-value: 3.71e-04

                         10        20        30
                 ....*....|....*....|....*....|..
gi 446398238  30 LWNQPAGHLE-ADETLVEAAARELWEETGISA 60
Cdd:cd24158   65 LWELPAGLLDvAGEPPLEAAARELAEEADLEA 96

UDP-X diphosphatase; UDP-X diphosphatase hydrolyzes UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-alanine, the last step of the Mur pathway of peptidoglycan biosynthesis. 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.

Pssm-ID: 467601 [Multi-domain] Cd Length: 128 Bit Score: 37.76 E-value: 4.88e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 446398238   4 PHVTVACVVHAEGKFLVVEETinGKALWNQPAGHLEADETLVEAAARELWEETGISA 60
Cdd:cd18891    1 PKVDVRAFIQNENKVLLVQDK--HTKEWALPGGFAEVGLSPKENILKEVKEETGLHV 55

Predicted NTP pyrophosphohydrolase, NUDIX family [Nucleotide transport and metabolism, General function prediction only];

Pssm-ID: 443295 [Multi-domain] Cd Length: 153 Bit Score: 38.27 E-value: 5.34e-04

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 446398238  31 WNQPAGHLEADETLVEAAARELWEETGISAQPQHFI 66
Cdd:COG4119   38 WSIPKGEYEPGEDPLAAARREFAEETGVPAPDGPFI 73

8-oxo-dGTP diphosphatase MutT;

Pssm-ID: 182721 [Multi-domain] Cd Length: 129 Bit Score: 37.66 E-value: 5.63e-04

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 446398238  31 WNQPAGHLEADETLVEAAARELWEETGISA-QPQHF 65
Cdd:PRK10776  33 WEFPGGKIEAGETPEQALIRELQEEVGITVqHATLF 68

Bdellovibrio Bacteriovorus nucleoside diphosphate sugar hydrolase, and similar proteins; Bdellovibrio bacteriovorus nucleoside diphosphate sugar (NDPS) hydrolase Bd3179 has been shown to similarities to the Escherichia coli adenosine diphosphate ribose (ADPR) hydrolase and the guanosine diphosphate mannose (GDPM) hydrolase. It may have a role when Bdellovibrio degrades and metabolizes host cell. ADP-ribose pyrophosphatase (ADPRase) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

Pssm-ID: 467607 [Multi-domain] Cd Length: 173 Bit Score: 38.13 E-value: 6.12e-04

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 446398238  27 GKALWNQPAGHLEADETLVEAAARELWEETGISAQ 61
Cdd:cd24159   66 KRVFLEFPAGKIDPGEDTLETAKRELLEETGYEAQ 100

Mitochondrial ribosomal protein L46; Mitochondrial ribosomal protein L46 (MRP L46) is a component of the large subunit (39S) of the mammalian mitochondrial ribosome and a member of the NUDIX hydrolase superfamily. MRPs are thought to be involved in the maintenance of the mitochondrial DNA. In general, members of the NUDIX hydrolase superfamily require 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), which functions as a metal binding and catalytic site. MRP L46 appears to contain a modified NUDIX motif.

Pssm-ID: 467546 Cd Length: 142 Bit Score: 37.59 E-value: 7.54e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  18 FLVVEETiNGKALWNQPAGHLEADETLVEAAARELWEETG-------ISAQPQHFIRmHQWIAPDKTPFLR-FLFAIele 89
Cdd:cd04661   32 YLLVKQK-KGKGPWQFPQGDVEEGETLREAAERGLRELGGdnmntwfVGNAPIGVYK-YKYPKKTKEFGYKsFFLKG--- 106

                         90       100
                 ....*....|....*....|....
gi 446398238  90 QICPTQPHD-SDIdccRWVSAEEI 112
Cdd:cd04661  107 RFMPGQKKGvSDF---AWLTKEEL 127

Adp-ribose pyrophosphatase (ADPRase) found in Thermus thermophilus, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) such as found in extreme thermophile Thermus thermophilus (TtADPRase) catalyzes the hydrolysis of ADPR to AMP and ribose 5'-phosphate in the presence of Mg2+ and Zn2+ ions. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

Pssm-ID: 467608 [Multi-domain] Cd Length: 151 Bit Score: 37.48 E-value: 8.93e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   8 VACVVHAEGKFLVVEETIN--GKALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMhqWIAPDKTPFLRFLFA 85
Cdd:cd24160   24 VAVLALREGRMLFVRQMRPavGAATLEIPAGLIDPGETPEEAARRELAEETGLSGDLTYLTRF--YVSPGFCDEKLHVFL 101

                         90       100       110
                 ....*....|....*....|....*....|
gi 446398238  86 IELEQICPTQPHDSDIDCCRWVSAEEILQA 115
Cdd:cd24160  102 AENLREVEAHPDEDEAIEVVWMRPEEVLER 131

nudix hydrolase; Provisional

Pssm-ID: 215602 Cd Length: 291 Bit Score: 37.88 E-value: 1.17e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 446398238   4 PHVTVACVVHAEG-KFLVVEETIN---GKALWNQPAGHLEADE-TLVEAAARELWEETGISAQPQHFIRMHQWIAPD 75
Cdd:PLN03143 129 PAVAVLILLESEGeTYAVLTEQVRvpvGKFVLELPAGMLDDDKgDFVGTAVREVEEETGIKLKLEDMVDLTAFLDPS 205

Nucleoside diphosphate-linked moiety X)) motif 19; Acyl CoA diphosphohydrolase (also known as NUDIX (nucleoside diphosphate linked moiety X))-type motif 10; Nudt19; testosterone-regulated protein rp2) has activity towards CoA, oxidized CoA and a wide range of CoA esters, including choloyl-CoA and branched-chain fatty-acyl-CoA esters. CoA is the major acyl carrier in mammals and a key cofactor in energy metabolism. Dynamic regulation of CoA in different tissues and organs supports metabolic flexibility. 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.

Pssm-ID: 467582 [Multi-domain] Cd Length: 159 Bit Score: 37.23 E-value: 1.26e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  31 WNQPAGHLEADETLVEAAARELWEETGISaqpqhFIRMHqWIAPDKTPfLRF---LFAIELEQICPTQPHDSDIDCCRWV 107
Cdd:cd18870   60 ASRPGKSDPEARALRIAAIRETFEETGLL-----LAWAR-WITPPGMP-RRFdtrFFLAPLPAGQEPVHDGGETVEARWV 132

                         90
                 ....*....|....*..
gi 446398238 108 SAEEIL-QASNLRSPLV 123
Cdd:cd18870  133 TPREALeAAEAGEIPLP 149

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.

Pssm-ID: 467565 [Multi-domain] Cd Length: 123 Bit Score: 36.50 E-value: 1.59e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 446398238  29 ALWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKTPFLRFLFAIELEQ 90
Cdd:cd04682   28 NLWDLPGGGREGDETPFACVLRELREELGLALPEDRLVWERVYPSNHNPGRQSWFFVARLPA 89

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.

Pssm-ID: 467594 Cd Length: 136 Bit Score: 36.68 E-value: 1.65e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238   6 VTVACVVHAEGKFLVVEETINGKALWnqPAGHLEADETLVEAAARELWEETGISAQPQHFIRM--HQWIAPDKTPF-LRF 82
Cdd:cd18883    1 YTARGVIISDEHLLLARVKGDDKTFL--PGGHIEIGESAEIALVRELREELGLSCKVGRYLGAveNQWQDKEVIHVeLNH 78

                         90
                 ....*....|....*..
gi 446398238  83 LFAIELEQICPTQPHDS 99
Cdd:cd18883   79 LFEVELQDLHTSDTPES 95

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

Pssm-ID: 467529 [Multi-domain] Cd Length: 162 Bit Score: 36.32 E-value: 2.40e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  36 GHLEADETLVEAAARELWEETGISAQPQHFIRMHQWIAPDKTPFlrflfaIELEqICP---------TQPHDSDIDCCRW 106
Cdd:cd02885   64 SHPLPGEGVEDAAQRRLREELGIPVCDLEELPRFRYRATDDNGL------VEHE-IDHvfvgradgdPVPNPEEVSDYRW 136


                 ....*....
gi 446398238 107 VSAEEILQA 115
Cdd:cd02885  137 VSLEELREL 145

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.

Pssm-ID: 467589 [Multi-domain] Cd Length: 141 Bit Score: 35.80 E-value: 2.93e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446398238  31 WNQPAGHLEADETLVEAAARELWEETGISAqpqHFIRMHQWIAPDKTPFLRFLFAIELEQICPTQPHDSDIDCCRWVSAE 110
Cdd:cd18877   49 WALPGGARDSGETPEAAALRETEEETGLDA---DTLRVVGTHVDDHGGWSYTTVLASAPEPLPVRPANEESVELRWVPLD 125


                 ..
gi 446398238 111 EI 112
Cdd:cd18877  126 EV 127

translation initiation factor IF-2B alpha subunit; Eukaryotic translation initiation factor 2B subunit alpha (EIF2B1) is one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. 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.

Pssm-ID: 467584 [Multi-domain] Cd Length: 129 Bit Score: 35.69 E-value: 3.23e-03

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 446398238  30 LWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIR 67
Cdd:cd18872   28 RWAGISGSIESDDPPLAAAWREIREETGLTPEDVELLR 65

NAD(+) diphosphatase;

Pssm-ID: 234699 [Multi-domain] Cd Length: 256 Bit Score: 36.37 E-value: 3.84e-03

                         10        20
                 ....*....|....*....|....
gi 446398238  35 AGHLEADETLVEAAARELWEETGI 58
Cdd:PRK00241 162 AGFVEVGETLEQCVAREVMEESGI 185

adenosine nucleotide hydrolase NudE; Provisional

Pssm-ID: 183303 Cd Length: 185 Bit Score: 35.94 E-value: 4.03e-03

                         10        20        30
                 ....*....|....*....|....*....|....
gi 446398238  34 PAGHLEADETLVEAAARELWEETGISAQPQHFIR 67
Cdd:PRK11762  79 PKGLIDPGETPLEAANRELKEEVGFGARQLTFLK 112

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.

Pssm-ID: 467599 [Multi-domain] Cd Length: 127 Bit Score: 34.89 E-value: 5.95e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 446398238  15 EGKFLVVEETiNGKalWNQPAGHLEADETLVEAAARELWEETGISAQPQHFIRMHQW 71
Cdd:cd18889   12 DDKILLVQEK-DGR--WSLPGGWVDVNQSIKENTIKEAKEEAGLDVEPKRIIAVLDR 65

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

Pssm-ID: 442065 [Multi-domain] Cd Length: 288 Bit Score: 35.66 E-value: 7.20e-03

                         10        20
                 ....*....|....*....|....
gi 446398238  35 AGHLEADETLVEAAARELWEETGI 58
Cdd:COG2816  188 AGFVEPGETLEQAVRREVFEEVGV 211

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.

Pssm-ID: 467547 Cd Length: 147 Bit Score: 34.86 E-value: 8.27e-03

                         10        20        30
                 ....*....|....*....|....*....|
gi 446398238  31 WNQPAGHLEADETLVEAAARELWEETGISA 60
Cdd:cd04662   35 WSIPKGEVEPGEDPLAAARREFEEETGFPA 64

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

Pssm-ID: 467603 [Multi-domain] Cd Length: 187 Bit Score: 34.81 E-value: 9.77e-03

                         10        20        30
                 ....*....|....*....|....*....|...
gi 446398238  34 PAGHLEADETLVEAAARELWEETGISAQPQHFI 66
Cdd:cd24155   81 VAGMIDAGETPEDVARREAEEEAGLTLDALEPI 113