NCBI Conserved Domain Search

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: 175.95 E-value: 1.36e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   8 WLAVGGLVaTKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRNEISDNMI 87
Cdd:cd04691     1 WLGVGGVV-VKEGKVLLVKRAYGPGKGRWTLPGGFVEEGETLDEAIVREVLEETGIDAKPVGIIGVRSGVIRDGKSDNYV 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1207723700  88 IFLLEPEGENIIVQEKELSEVAFLHPDTIADDPNTSLLIKYL 129
Cdd:cd04691    80 VFLLEYVGGEPKPDERENSEAGFLTLEEALANEDIADMSREL 121

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 86.96 E-value: 1.29e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   1 MEKRGKVwlAVGGLVATKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRN 80
Cdd:COG1051     1 MTKVPKV--AVDAVIFRKDGRVLLVRRADEPGKGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHPDRG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1207723700  81 EIsdNMIIFLLEPEGENiIVQEKELSEVAFLHPDTIADDP 120
Cdd:COG1051    79 HV--VSVAFLAEVLSGE-PRADDEIDEARWFPLDELPELA 115

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: 86.05 E-value: 3.34e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   9 LAVGGLVATKDGRWLFVKKKYSGlKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSG-VIRNEISDNMI 87
Cdd:cd04670     3 VGVGGLVINENNEVLVVQEKYGG-PGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFRHQhPGRFGKSDLYF 81

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1207723700  88 IFLLEPEGENIIV-QEKELSEVAFLHPDTIADDPNTSL 124
Cdd:cd04670    82 VCRLRPLSDEEIKiCPEEIAEAKWMPLEEYLKQPNVSQ 119

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: 80.14 E-value: 4.17e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   9 LAVGGLVATKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRNEISDN-MI 87
Cdd:cd02883     1 VAVGAVVFDDEGRVLLVRRSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEGRHVvVL 80

                          90       100
                  ....*....|....*....|....*
gi 1207723700  88 IFLLEP-EGENIIVQEKELSEVAFL 111
Cdd:cd02883    81 VFLARVvGGEPPPLDDEEISEVRWV 105

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 78.29 E-value: 4.10e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   9 LAVGGLVATKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRNEISDN--- 85
Cdd:pfam00293   4 VAVGVVLLNEKGRVLLVRRSKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRFPdeh 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1207723700  86 --MIIFLLEPEGENIIVQEKELSEVAFLHPDTIADDPNTSLLIKYL 129
Cdd:pfam00293  84 eiLYVFLAEVEGELEPDPDGEVEEVRWVPLEELLLLKLAPGDRKLL 129

ADP-ribose pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase; EC 3.6.1.13) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the NUDIX hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also contains a 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. In humans, there are four distinct ADPRase activities, three putative cytosolic (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). ADPRase-m is also known as NUDT9. It can be distinugished from the cytosolic ADPRase by a N-terminal target sequence unique to mitochondrial ADPRase. NUDT9 functions as a monomer.

Pssm-ID: 467557 [Multi-domain] Cd Length: 128 Bit Score: 73.32 E-value: 2.68e-17

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207723700   8 WLAVGGLVaTKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRNE 81
Cdd:cd04673     1 IVAVGAVV-FRDGRVLLVRRGNPPDAGLWSFPGGKVELGETLEDAALRELREETGLEAEVVGLLTVVDVIERDE 73

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: 64.82 E-value: 4.27e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  10 AVGGLVATKDGRWLFVKKKYSGlKGKWSLPAGFVNEGETVDEAVKREVLEETGIvaHVKGIIGVRS------GVIrneis 83
Cdd:cd03429     3 AVIVLVTNGEDKILLARQPRWP-PGRYSLLAGFVEPGETLEEAVRREVKEEVGL--RVKNVRYVGSqpwpfpSSL----- 74

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1207723700  84 dnMIIFLLEPEGENIIVQEKELSEVAFLHPDTIAD 118
Cdd:cd03429    75 --MLGFTAEADSGEITVDDDELEDARWFSRDELPE 107

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: 61.59 E-value: 1.32e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  10 AVGGLVATKDGRWLFVKK-KYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIG-VRSGVIRNEIsdnMI 87
Cdd:COG0494    15 AVVVVLLDDDGRVLLVRRyRYGVGPGLWEFPGGKIEPGESPEEAALRELREETGLTAEDLELLGeLPSPGYTDEK---VH 91

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1207723700  88 IFLLE---PEGENIIVQEKELSEVAFLHPDTIAD 118
Cdd:COG0494    92 VFLARglgPGEEVGLDDEDEFIEVRWVPLDEALA 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: 467588 [Multi-domain] Cd Length: 121 Bit Score: 60.29 E-value: 2.05e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   9 LAVGGLVATKDGRWLFVKKKYsglKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRNEISDnMII 88
Cdd:cd18876     1 AAAGALFTDAAGRVLLVKPTY---KDGWELPGGVVEAGESPLQAARREVREELGLDVPVGRLLAVDWVPPAGGGDD-AVL 76

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1207723700  89 FL-----LEPEG-ENIIVQEKELSEVAFLHPDTIAD 118
Cdd:cd18876    77 FVfdggvLTPEQaAAIRLQDEELSAYRFVTPEEAAE 112

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: 60.02 E-value: 3.28e-12

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207723700  11 VGGLVATKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGV 73
Cdd:cd04671     3 VAAVIINEQGEVLMIQEAKRSCRGKWYLPAGRVEPGESIVEAAKREVKEETGLKCEPSTLLSV 65

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: 59.89 E-value: 4.87e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207723700  10 AVGGLVATkDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAH 66
Cdd:cd04681     8 AVGVIIRN-EGEILFVRRAKEPGKGKLDLPGGFVDPGESAEEALRRELREELGLKIP 63

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: 59.48 E-value: 6.59e-12

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1207723700  23 LFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGI 63
Cdd:cd18873    20 LLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETGL 60

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

Pssm-ID: 467560 [Multi-domain] Cd Length: 137 Bit Score: 58.68 E-value: 1.43e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  11 VGGLVATKDGRWLFVKKKYsglKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSG-----VIRN--EIS 83
Cdd:cd04677    15 AAVIILNEQGRILLQKRTD---TGDWGLPGGAMELGESLEETARREVFEETGLTVEELELLGVYSGkdlyyTYPNgdEVY 91

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1207723700  84 DNMIIFLLEPEGENIIVQEKELSEVAFLHPD 114
Cdd:cd04677    92 NVTAVYLVRDVSGELKVDDEESLELRFFSLD 122

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: 467562 [Multi-domain] Cd Length: 126 Bit Score: 57.70 E-value: 2.58e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207723700  13 GLVATKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGV 73
Cdd:cd04679     6 GAAILDDGRLLLVLRLRAPEAGHWGLPGGKVDWLETVEDAVRREILEELGLEIELTRLLCV 66

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: 58.18 E-value: 2.68e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207723700  10 AVGGLVATKDGRWLFVKKkysGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSG 76
Cdd:cd04676    19 SVAAVILNEDGRILLQRK---GGLGLWSLPAGAIEPGEHPAEAVIREVREETGLLVKPTRLLGVFGG 82

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

Pssm-ID: 442065 [Multi-domain] Cd Length: 288 Bit Score: 59.16 E-value: 6.43e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  34 GKWSLPAGFVNEGETVDEAVKREVLEETGIvaHVKGIIGVRS-------GVirneisdnMIIFLLEPEGENIIVQEKELS 106
Cdd:COG2816   182 GRYSLLAGFVEPGETLEQAVRREVFEEVGV--RVKNVRYVGSqpwpfpsSL--------MLGFTAEADSGEITVDGDEIE 251

                          90
                  ....*....|..
gi 1207723700 107 EVAFLHPDTIAD 118
Cdd:COG2816   252 DARWFSRDELPA 263

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: 55.66 E-value: 1.23e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  11 VGGLVATKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRNEIsdnMIIF- 89
Cdd:cd04511     4 VVGCLPEWEGKVLLCRRAIEPRKGYWTLPAGFMELGETTEQGAARETREEAGARVEIGSLYAVYSLPHISQV---YIIFr 80

                          90       100
                  ....*....|....*....|....*....
gi 1207723700  90 --LLEPEGEniivQEKELSEVAFLHPDTI 116
Cdd:cd04511    81 arLLSPDFS----PGPESLEVRLFDEEEI 105

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: 55.61 E-value: 1.99e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207723700  15 VAT---KDGRWLFVKKKYSGlKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGV 73
Cdd:cd03675     3 VAAvveRDGRFLLVEEETDG-RLVLNQPAGHLEPGESLLEAAIRETLEETGWEVEPTALLGI 63

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: 55.26 E-value: 2.44e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207723700  11 VGGLVATKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRNE 81
Cdd:cd04678     5 VGVIVLNDDGKVLLGRRKGSHGAGTWALPGGHLEFGESFEECAAREVLEETGLEIRNVRFLTVTNDVFEEE 75

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: 54.90 E-value: 3.55e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   8 WL-AVGGLVATKDGRWLFVKKKYSGlkgKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVR-SGVIRNEISDN 85
Cdd:cd18879    17 WLpGVTAVVLRDAGRVLLVRRADNG---RWTPVTGIVEPGEQPADAAVREVLEETGVDVEVERLASVGaSPPVTYPNGDQ 93

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1207723700  86 M----IIFLLEPEGENIIVQEKELSEVAFLHPD 114
Cdd:cd18879    94 CqyldLTFRCRPVGGEARVNDDESLEVGWFPVD 126

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: 53.72 E-value: 7.63e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207723700  18 KDGRWLFVKKKysgLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVR 74
Cdd:cd04672    11 KDGKILLVREK---SDGRWTLPGGWADVGLSPAENAVKEVREESGYEVRARKLLAVF 64

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: 53.01 E-value: 1.32e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   9 LAVGGLVAtKDGRWLFVKKKySGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRNEISDNMII 88
Cdd:cd04699     3 VSVKGVIF-DNGRVLLLRRS-RAGAGEWELPGGRLEPGESPEEALKREVKEETGLDVSVGELLDTWTFELDPDKGVFIVT 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1207723700  89 FLLEPEGENIIVQEkELSEVAFLHPDTIAD 118
Cdd:cd04699    81 YLCRLVGGEVTLSD-EHEEYEWVTPEELAE 109

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: 53.33 E-value: 1.34e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   9 LAVGGLV---ATKDGRWLFVKKKYSGlkgKWSLPAGFVNEGETVDEAVKREVLEETGIvahvKGIIGVRSGVIRNEISDN 85
Cdd:cd03673     2 EAAGGVVwrgRGGGGEVLLIHRPRYD---DWSLPKGKLEPGETPEEAAVREVEEETGL----RVRLGRPLGTTRYTYTRK 74

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1207723700  86 MII-------FLLEPE-GENIIVQEKELSEVAFLHPD 114
Cdd:cd03673    75 GKGilkkvhyWLMRALgGEFLPQPEEEIDEVRWLPPD 111

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

Pssm-ID: 467586 [Multi-domain] Cd Length: 125 Bit Score: 53.06 E-value: 1.55e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  11 VGGLVATKDGRWLFVK-KKYSGLkgkWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRNEISDN---- 85
Cdd:cd18874     5 VGALIFNPDGKVLLVRsHKWNDL---YGIPGGKVEWGETLEEALKREVKEETGLDITDIRFILVQESINSEEFHKPahfv 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1207723700  86 MIIFLLEPEGENIIVQEkELSEVAFLHPDTIADDP---NTSLLIK 127
Cdd:cd18874    82 FVDYLARTDSSEVVLNE-EAVEYLWVEPEEALKYPlnsFTRLLLE 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: 467558 [Multi-domain] Cd Length: 118 Bit Score: 52.46 E-value: 2.22e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207723700  34 GKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKgiiGVRSGVIRNEISDNMIIFLLEPE 94
Cdd:cd04674    29 GELALPGGYIEYGETWQEAAVRELREETGVEADAA---EVRLFAVRSAPDGTLLIFGLLPE 86

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: 51.87 E-value: 3.48e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207723700   9 LAVGGLVATKDGRWLFVKKKYsgLKGkWSLPAGFVNEGETVDEAVKREVLEETGIVA 65
Cdd:cd04680     1 LGVRAIVLDDAGRVLLVRHTY--VPG-WYLPGGGVDKGETAEEAARRELREEAGVVL 54

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: 51.10 E-value: 6.63e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1207723700  15 VATKDGRWLFVKKKYsglKGKWSLPAGFVNEGETVDEAVKREVLEETGIV 64
Cdd:cd04665     6 IARYKGKWLFTRHKE---RRGWEFPGGKREPGETIEEAARRELYEETGAV 52

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: 51.13 E-value: 7.05e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  17 TKDGRWLFVKKKysglKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAH-VKGIIGVRSGVIRNEisdnmiIFLLEPEG 95
Cdd:cd04667     8 RRGDRILLVARR----GGRWLLPGGKIEPGESPLEAAIRELKEETGLAALsLLYLFEHEGPHKLHH------VFLAEAPD 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1207723700  96 ENIIVQEKELSEVAFLHPDTIAD---DPNTSLLIKYLFEG 132
Cdd:cd04667    78 GGRPRPGNEIARCRWVSADQLRDlnlSRATRLIVRRYLRR 117

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

Pssm-ID: 467595 [Multi-domain] Cd Length: 125 Bit Score: 50.87 E-value: 9.71e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  11 VGGLVATkDGRWLFVKKKySGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRNEIsdnMIIFL 90
Cdd:cd18884    12 VAAIVEH-DGHIVLARNK-AWPEGWYGLVTGFLEAGESPEEAVLREVKEELGLDGHEAKFIGHYAFPERNQL---IIAYH 86

                          90       100
                  ....*....|....*....|....*..
gi 1207723700  91 LEPEGEniIVQEKELSEVAFLHPDTIA 117
Cdd:cd18884    87 VRARGN--VKLNEELDDYKIVPIDKLR 111

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: 50.64 E-value: 1.64e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207723700  11 VGGLVATKDGRwLFVKKKySGLKGKWSLPAGFVNEGETVDEAVKREVLEETGI-VAHVKgIIGVRSGVIRNEISDNMI 87
Cdd:cd03671     6 VGIVLFNRDGQ-VLVGRR-IDVPGAWQFPQGGIDEGEDPEEAALRELYEETGLsPEDVE-IIAETPDWLTYDLPEDLI 80

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: 50.60 E-value: 1.90e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   9 LAVGGLVATKDGRWL-----FVKKKYSGLkgkWSL-PAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSgVIRNEI 82
Cdd:cd04693    30 LVVHVWIFNSDGEILiqqrsPDKKGFPGM---WEAsTGGSVLAGETSLEAAIRELKEELGIDLDADELRPILT-IRFDNG 105

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1207723700  83 SDNMIIFLLEPEGENIIVQEKELSEVAFLHPDTIADDPNTSLLIKYLFE 131
Cdd:cd04693   106 FDDIYLFRKDVDIEDLTLQKEEVQDVKWVTLEEILEMIESGEFIPYQKY 154

NAD(+) diphosphatase;

Pssm-ID: 234699 [Multi-domain] Cd Length: 256 Bit Score: 51.78 E-value: 2.12e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  34 GKWSLPAGFVNEGETVDEAVKREVLEETGIvaHVKGIIGV--------RSgvirneisdNMIIFLLEPEGENIIVQEKEL 105
Cdd:PRK00241  156 GVYTVLAGFVEVGETLEQCVAREVMEESGI--KVKNLRYVgsqpwpfpHS---------LMLGFHADYDSGEIVFDPKEI 224

                          90       100
                  ....*....|....*....|.
gi 1207723700 106 SEVAFLH---------PDTIA 117
Cdd:PRK00241  225 ADAQWFRydelpllppSGTIA 245

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: 50.20 E-value: 2.28e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207723700  10 AVGGLVATKDGRWLFVK------KKYSglkgkWSLPAGFVNEGETVDEAVKREVLEETGIVA 65
Cdd:cd03424     4 AVAVLAITDDGKVVLVRqyrhpvGRVL-----LELPAGKIDPGEDPEEAARRELEEETGYTA 60

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

Pssm-ID: 467542 [Multi-domain] Cd Length: 130 Bit Score: 49.18 E-value: 4.36e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  20 GRWLFVK-KKYsglkGKWSLPAGFVNEGETVDEAVKREVLEETGIVAhvkGIIGVRSGVI----RNEISDNM-------- 86
Cdd:cd03674    14 GKVLLVHhRKL----GRWLQPGGHVEPDEDPLEAALREAREETGLDV---ELLSPLSPDPldidVHPIPANPgepahlhl 86

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1207723700  87 -IIFLLEPEGENIIVQEKELSEVAFLHPDTIADD 119
Cdd:cd03674    87 dVRYLAVADGDEALRKSDESSDVRWFPLDELEEL 120

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: 49.21 E-value: 5.03e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207723700  15 VATKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRS 75
Cdd:cd04686     7 IIIRNDKLLLIRKTRGPYQGRYDLPGGSQEFGESLEDALKREFAEETGMTVTSYDNLGVYD 67

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: 48.77 E-value: 7.50e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207723700  14 LVATKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVA---HVKGIIGVRSG 76
Cdd:cd18886     5 CFIIRDDEVLLLNRNKKPNMGKWNGVGGKLEPGESPEECAIREVFEETGLELedlQLRGIVTFPSF 70

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: 48.29 E-value: 1.06e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  19 DGRWLFVKKKySGL-KGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVrsgvirneisdnmIIFLLEPEGEN 97
Cdd:cd03427    12 DDRVLLGLKK-RGFgAGKWNGFGGKVEPGETIEEAAVRELEEEAGLTATELEKVGR-------------LKFEFPDDPEA 77


                  ...
gi 1207723700  98 IIV 100
Cdd:cd03427    78 MDV 80

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: 47.91 E-value: 1.13e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207723700  18 KDGRWLFVKkkYSGLKGK-WSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVR 74
Cdd:cd18880    10 EDGKLLLVK--HRDEGGIfYILPGGGQEHGETLPEALKRECLEETGLDVEVGDLLFVR 65

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: 48.16 E-value: 1.15e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207723700  18 KDGRWLFVKKKYSGLkgkWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGV 73
Cdd:cd18891    11 NENKVLLVQDKHTKE---WALPGGFAEVGLSPKENILKEVKEETGLHVEVERLLAV 63

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: 47.60 E-value: 1.69e-07

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1207723700  34 GKWSLPAGFVNEGETVDEAVKREVLEETGIVAH 66
Cdd:cd04683    26 GWWHLPAGHVEAGETVRAAAVREAKEELGVEID 58

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: 46.90 E-value: 3.07e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   9 LAVGGLVATKDGRWLFVKKKYSGLK--GKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVK---GIIGVRSGVIRNEIS 83
Cdd:cd04694     3 VGVVVLIEDSDDRVLLTRRAKHMRTfpGVWVPPGGHVELGESLLEAGLRELQEETGLEVSDIqslSLLGLWESVYPTLLS 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1207723700  84 DN------MIIFLL------EPEGENIIVQEKELSEVAFLHPDTIAD 118
Cdd:cd04694    83 IGlpkrhhIVVYYLvklsesHENQEQLKLQEDEVDAAVWLPKSLLAK 129

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: 46.29 E-value: 5.08e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207723700  11 VGGLVATKDGRWLFVKKKYSG-LKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGV 73
Cdd:cd03425     3 VVAAIIVDDGRVLIAQRPEGKhLAGLWEFPGGKVEPGETPEQALVRELREELGIEVEVGEPLGT 66

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: 46.35 E-value: 9.01e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   9 LAVGGLVATKDGRWLFVK----KKYSGlkGKWSLP-AGFVNEGETVDEAVKREVLEETGIVAH----VKGII----GVRS 75
Cdd:COG1443    30 RAFSVFVFNSDGRLLLQRraltKDHWP--GLWDNTvCGHPRAGETYEEAAVRELEEELGITVDddlrPLGTFryraVDAN 107

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1207723700  76 GVIRNEISDnmiIFLLEPEGEnIIVQEKELSEVAFLHPDTIADD 119
Cdd:COG1443   108 GLVENEFCH---VFVARLDGP-LTPQPEEVAEVRWVTLEELLAL 147

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 47.31 E-value: 9.01e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207723700  15 VATKDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIvahvKGIIGVRSGVIR 79
Cdd:PRK05379  209 VVVQSGHVLLVRRRAEPGKGLWALPGGFLEQDETLLDACLRELREETGL----KLPEPVLRGSIR 269

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: 44.94 E-value: 1.66e-06

                          10        20
                  ....*....|....*....|....*....
gi 1207723700  34 GKWSLPAGFVNEGETVDEAVKREVLEETG 62
Cdd:cd18882    30 GYWGLFGGHLEPGETPEEAIRRELEEEIG 58

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: 44.33 E-value: 2.63e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207723700  11 VGGLVATKDGRWLFVKKKysgLKGKWSLPAGFVNEGETVDEAVKREVLEETG-IVAHVK 68
Cdd:cd18890     5 IRAVVFNDKEEILLVKEK---EDGKWTLPGGWADVGYTPTEVAAKEVEEETGlEVSPKK 60

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 46.02 E-value: 2.76e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207723700   1 MEKRGKVwlaVGGLVATKDGRWLFVK----KKYSGLkgkWSLPAGFVNEGETVDEAVKREVLEETGIVAHV 67
Cdd:PRK08999    1 SMKRIHV---AAGVIRDADGRILLARrpegKHQGGL---WEFPGGKVEPGETVEQALARELQEELGIEVTA 65

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: 44.14 E-value: 3.50e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207723700  18 KDGRWLFVKKKysglKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGV 73
Cdd:cd18889    11 KDDKILLVQEK----DGRWSLPGGWVDVNQSIKENTIKEAKEEAGLDVEPKRIIAV 62

RNA pyrophosphohydrolase; Reviewed

Pssm-ID: 234820 [Multi-domain] Cd Length: 156 Bit Score: 43.61 E-value: 7.98e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207723700  11 VGGLVATKDGRwLFVKKKYsGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIV-AHVKgIIGVRSGVIRNEISDNMI 87
Cdd:PRK00714   11 VGIILLNRQGQ-VFWGRRI-GQGHSWQFPQGGIDPGETPEQAMYRELYEEVGLRpEDVE-ILAETRDWLRYDLPKRLV 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: 467574 [Multi-domain] Cd Length: 142 Bit Score: 42.93 E-value: 1.22e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  14 LVATKDGRWLFVKKKySGLK----GKWSLP-AGFVNEGETVDEAVKREVLEETGIVAHVKGI--IGVRSGVIR------N 80
Cdd:cd04692    32 WLVNPEEGRLLLQKR-SANKddfpGLWDISaAGHIDAGETYEEAAVRELEEELGLTVSPEDLifLGVIREEVIggdfidN 110

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1207723700  81 EISDnmiIFLLEPEG--ENIIVQEKELSEVAFL 111
Cdd:cd04692   111 EFVH---VYLYETDRplEEFKLQPEEVAGVVFV 140

8-oxo-dGTP diphosphatase MutT;

Pssm-ID: 182721 [Multi-domain] Cd Length: 129 Bit Score: 42.28 E-value: 1.44e-05

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1207723700  34 GKWSLPAGFVNEGETVDEAVKREVLEETGIVA 65
Cdd:PRK10776   31 GKWEFPGGKIEAGETPEQALIRELQEEVGITV 62

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: 42.61 E-value: 1.53e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1207723700  33 KGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIG 72
Cdd:cd04684    36 NGGYFLPGGGIEPGETPEEALHREVLEETGWEIEIGEFLG 75

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: 41.90 E-value: 2.47e-05

                          10        20
                  ....*....|....*....|....*.
gi 1207723700  38 LPAGFVNEGETVDEAVKREVLEETGI 63
Cdd:cd04663    30 VPKGTVEPGESPEEAALRELAEETGL 55

Uncharacterized conserved protein [Function unknown];

Pssm-ID: 443287 [Multi-domain] Cd Length: 170 Bit Score: 42.08 E-value: 2.60e-05

                          10        20
                  ....*....|....*....|....*..
gi 1207723700  37 SLPAGFVNEGETVDEAVKREVLEETGI 63
Cdd:COG4111     1 ALPGGFVREHESLEDAARRWLAEQTGL 27

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: 41.39 E-value: 3.76e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207723700  10 AVGGLVATKDGRWLFVKKkYSGLKGKWSL--PAGFVNEGETVDEAVKREVLEETGIVAH 66
Cdd:cd24161     5 AVGVLPITDDGEVVLVEQ-YRYPLGGWSWeiPAGGWPEGEDPEEAARRELREETGLRAE 62

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: 467570 [Multi-domain] Cd Length: 130 Bit Score: 41.38 E-value: 3.81e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207723700  36 WSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGV------RSGVIRNEIsdnMIIFLLEPEGENIIVQEKELSE 107
Cdd:cd04688    26 YRLPGGRVEFGETSEDALVREFKEELGVEVEVVRLLFVvenfftYDGKPFHEI---GFYYLVELSDEALYEQDIFFLE 100

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: 41.08 E-value: 3.83e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  17 TKDGRWLFVKK--KYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAhvKGIIGVRSGVIRnEISDNMI------- 87
Cdd:cd18872     8 FHDGKVLLFRRsdKVGTYQGRWAGISGSIESDDPPLAAAWREIREETGLTP--EDVELLRQGKPF-EFTDESLgrewtvh 84

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1207723700  88 IFLLEPEGENIIVQEKELSEVAFLHPDTIADDP 120
Cdd:cd18872    85 PFLFRLKDDRAIKLDWEHTEWEWVDPTDILDYE 117

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

Pssm-ID: 467587 [Multi-domain] Cd Length: 144 Bit Score: 41.40 E-value: 4.09e-05

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1207723700  25 VKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGI 63
Cdd:cd18875    18 VLDRVKKDWGGYTFPGGHVEPGESFVDSVIREVKEETGL 56

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: 41.00 E-value: 4.65e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1207723700  12 GGLVATKDG---RWLFVKKKYSGlkgKWSLPAGFVNEGETVDEAVKREVLEETGI 63
Cdd:cd03428     6 GAIIYRRDNgeiEFLLLQHSYGG---HWDFPKGHVEPGESELETALRETKEETGL 57

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

Pssm-ID: 467589 [Multi-domain] Cd Length: 141 Bit Score: 40.80 E-value: 6.36e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1207723700  34 GKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVR 74
Cdd:cd18877    47 GTWALPGGARDSGETPEAAALRETEEETGLDADTLRVVGTH 87

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: 40.16 E-value: 1.06e-04

                          10        20
                  ....*....|....*....|....*...
gi 1207723700  38 LPAGFVNEGETVDEAVKREVLEETGIVA 65
Cdd:cd18888    37 FPAGLVDPGESPEQAALRELKEETGYTG 64

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: 39.83 E-value: 1.14e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  18 KDGRWLFVKKKysGlKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVrsGVIR------NEISDNMIIFLL 91
Cdd:cd04690    10 KDGRLLLVRKR--G-TDAFYLPGGKREPGETPLQALVRELKEELGLDLDPDSLRFL--GTFEapaanePGTTVRMTCFTA 84

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1207723700  92 EPEGEniIVQEKELSEVAFLHPDTIADDPNTSLLIKYLF 130
Cdd:cd04690    85 DYDGE--PQPAAEIEELRWLDPADPDDDRLAPLLREIVL 121

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: 39.86 E-value: 1.18e-04

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1207723700  36 WSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIG 72
Cdd:cd04685    30 WFTPGGGVEPGESPEQAAVRELREETGLRLEPDDLGG 66

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: 39.89 E-value: 1.33e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  10 AVGGLVATKDGRWLFVKKK----YSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGIIGVRSGVIRNEISDN 85
Cdd:cd04700    15 AAGVVLLNERGDILLVQEKgisgHPEKAGLWHIPSGAVEDGENPQDAAVREACEETGLRVRLVKFLGAYLGRFPDGVLVL 94

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1207723700  86 MIIFLLEPEGENII--VQEKELSEVAFLHPDTIAD 118
Cdd:cd04700    95 RHVWLAEPEPGQVLapAFTDEIAEASFVSREEFAQ 129

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

Pssm-ID: 443295 [Multi-domain] Cd Length: 153 Bit Score: 39.81 E-value: 1.77e-04

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1207723700  34 GKWSLPAGFVNEGETVDEAVKREVLEETGIVA 65
Cdd:COG4119    36 GAWSIPKGEYEPGEDPLAAARREFAEETGVPA 67

nucleoside triphosphatase NudI; Provisional

Pssm-ID: 185369 [Multi-domain] Cd Length: 141 Bit Score: 39.35 E-value: 2.37e-04

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1207723700  34 GKWSLPAGFVNEGETVDEAVKREVLEETG---IVAHVK 68
Cdd:PRK15472   31 GQWALSGGGVEPGERIEEALRREIREELGeqlLLTEIT 68

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

Pssm-ID: 467540 Cd Length: 144 Bit Score: 38.69 E-value: 3.28e-04

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1207723700  33 KGKWSLPAGFVNEGET-VDEAVkREVLEETGI 63
Cdd:cd03672    25 NSSWGFPKGKINKDESdADCAI-REVYEETGF 55

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: 39.29 E-value: 3.55e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1207723700  19 DGRWLFVKKKYSGLKGK-WSLPAGFVNEGETVDEAVKREVLEETGIVA 65
Cdd:cd24159    52 DGRVVMERQYRYPLKRVfLEFPAGKIDPGEDTLETAKRELLEETGYEA 99

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: 39.05 E-value: 4.30e-04

                          10        20        30
                  ....*....|....*....|....*....|
gi 1207723700  36 WSL--PAGFVNEGETVDEAVKREVLEETGI 63
Cdd:cd24155    76 WLLeiVAGMIDAGETPEDVARREAEEEAGL 105

ADP-ribose pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase;EC 3.6.1.13, also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 9/Nudt9, 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: 467538 [Multi-domain] Cd Length: 179 Bit Score: 38.85 E-value: 4.83e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1207723700  13 GLVATKDGR----WLFVKKKYSGLkgkWSLPAGFVNEGETVDEAVKREVLEET 61
Cdd:cd03670    36 GGNVERSGKkvleFVAIKRKDDGE---WAIPGGFVDPGEKVSDTLKREFYEEA 85

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

Pssm-ID: 182536 [Multi-domain] Cd Length: 135 Bit Score: 38.18 E-value: 5.19e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207723700   1 MEKRGKVWLAVGGLVATKDGRWLFvkkkysglkgkwslPAGFVNEGETVDEAVKREVLEETGIVAHVKGII 71
Cdd:PRK10546   11 IERDGKILLAQRPAHSDQAGLWEF--------------AGGKVEPGESQPQALIRELREELGIEATVGEYV 67

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: 38.37 E-value: 6.31e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700   2 EKRGKVWL--AVGGLVATKDGRwLFVKKKySGLK----GKWSL-PAGFVNEGETVDEAVKREVLEETGIV-AHVKGIigv 73
Cdd:cd04697    18 EMRRQKLIhrATYIVVRNAAGR-LLVQKR-TMDKdycpGYLDPaTGGVVGAGESYEENARRELEEELGIDgVPLRPL--- 92

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1207723700  74 rsGVIRNEISDNMI---IFLLEPEGEnIIVQEKELSEVAFLHPDTIADDPNT 122
Cdd:cd04697    93 --FTFYYEDDRSRVwgaLFECVYDGP-LKLQPEEVAEVDWMSEDEILQAARG 141

GDP-mannose glycosyl hydrolase; GDP-mannose glycosyl hydrolase, also known as GDP-mannose mannosyl hydrolase/GDPMH, is a member of the NUDIX hydrolase superfamily. This class of enzymes is unique from other members of the superfamily in two aspects. First, it contains a modified NUDIX signature sequence. The slight changes to the conserved sequence motif, GX5EX7REUXEEXGU, where U = I, L or V), are believed to contribute to the removal of all magnesium binding sites but one, retaining only the metal site that coordinates the pyrophosphate of the substrate. Secondly, it is not a pyrophosphatase that substitutes at a phosphorus; instead, it hydrolyzes nucleotide sugars such as GDP-mannose to GDP and mannose, cleaving the phosphoglycosyl bond by substituting at a carbon position. GDP-mannose provides mannosyl components for cell wall synthesis and is required for the synthesis of other glycosyl donors (such as GDP-fucose and colitose) for the cell wall. The importance of GDP-sugar hydrolase activities is thus closely related to the regulation of cell wall biosynthesis. Enzymes in this family are believed to regulate the concentration of GDP-mannose and GDP-glucose in the bacterial cell wall.

Pssm-ID: 467536 [Multi-domain] Cd Length: 146 Bit Score: 37.61 E-value: 1.02e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207723700  19 DGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGIVAHVKG--IIGV 73
Cdd:cd03430    26 DGEILLGKRNNRPAQGYWFVPGGRILKNETLDDAFKRIAREELGLEVTINAaeFLGV 82

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: 1.18e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1207723700  14 LVATKDGRWLFVKKKYSGLKGK-WSLPAGFVNEGETVDEAVKREVLEETGIVAHV 67
Cdd:cd24160    26 VLALREGRMLFVRQMRPAVGAAtLEIPAGLIDPGETPEEAARRELAEETGLSGDL 80

NUDIX hydrolase subfamily; Nucleoside triphosphatase NudI catalyzes the hydrolysis of nucleoside triphosphates, with a preference for pyrimidine deoxynucleoside triphosphates (dUTP, dTTP and dCTP). It is a members of the NUDIX hydrolase superfamily which 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: 467577 [Multi-domain] Cd Length: 134 Bit Score: 36.83 E-value: 1.74e-03

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1207723700  34 GKWSLPAGFVNEGETVDEAVKREVLEETG---IVAHV 67
Cdd:cd04696    29 GQWALSGGGVEPGERIEEALRREIREELGeqlILSDI 65

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: 36.18 E-value: 2.20e-03

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1207723700  36 WSLPAGFVNEGETVDEAVKREVLEETGIVAHVKGII 71
Cdd:cd04669    26 YVFPGGGIEPGETPEEAALREAVEELGLDVAVTLIT 61

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: 36.07 E-value: 3.17e-03

                          10        20        30
                  ....*....|....*....|....*....|
gi 1207723700  36 WSLPAGFVNEGETVDEAVKREVLEETGIVA 65
Cdd:cd04664    28 WQSVTGGIEDGETPWQAALRELKEETGLDP 57

nucleoside diphosphate-linked moiety X)) motif 16; U8 SnoRNA-decapping enzyme, also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 16/Nudt16, is encoded by the human NUDT16 gene and a RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. 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: 467581 Cd Length: 175 Bit Score: 36.18 E-value: 3.92e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1207723700  28 KYSGLKGkwsLPAGFVNEGETVDEAVKREVLEETGIVAHVKGI 70
Cdd:cd18869    33 RFDGLLG---FPGGFVDTGESLEEGLNRELREELGLAHAVFPV 72

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: 35.63 E-value: 4.68e-03

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1207723700  34 GKWSLPAGFVNEGETVDEAVKREVLEETGIVAHV 67
Cdd:cd04662    33 GAWSIPKGEVEPGEDPLAAARREFEEETGFPAPG 66

nudix hydrolase

Pssm-ID: 215184 [Multi-domain] Cd Length: 144 Bit Score: 35.61 E-value: 4.74e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1207723700  18 KDGRWLFVKKKYSGLKGKWSLPAGFVNEGETVDEAVKREVLEETGI 63
Cdd:PLN02325   18 KGNSVLLGRRRSSIGDSTFALPGGHLEFGESFEECAAREVKEETGL 63

UDP-glucose pyrophosphatase; UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as NUDIX (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: 467597 [Multi-domain] Cd Length: 181 Bit Score: 36.00 E-value: 4.81e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207723700  40 AGFVNEGETVDEAVKREVLEETG---IVAHVKGIIGVRSGV----IRN-----EISDNMIIFL---LEPEGENIIVQEKE 104
Cdd:cd18887    72 AGLVDKDKSLEEIAQEEILEECGydvPLEDLEKITSFRSGVgtsgSRQtlfyaEVTDDMKVSEgggVEEEGEMIEVVELP 151

                          90
                  ....*....|....*...
gi 1207723700 105 LSEV-AFLHPDTIADDPN 121
Cdd:cd18887   152 VEEAkEFIFDEEIPKPPG 169

dihydroneopterin triphosphate pyrophosphatase; Provisional

Pssm-ID: 236516 [Multi-domain] Cd Length: 148 Bit Score: 35.25 E-value: 7.36e-03

                          10        20
                  ....*....|....*....|....*
gi 1207723700  41 GFVNEGETVDEAVKREVLEETGIVA 65
Cdd:PRK09438   38 GSLEEGETPAQTAIREVKEETGIDV 62