NCBI Conserved Domain Search

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: 239.43 E-value: 4.63e-82

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  67 PKIGTRAAIFKDNKMLLVQESDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHYKGMYPYGISTV 146
Cdd:cd18889    1 PKIDTRAAIFKDDKILLVQEKDGRWSLPGGWVDVNQSIKENTIKEAKEEAGLDVEPKRIIAVLDRNKHNKPPYAYGIYKI 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 499475414 147 FFLCKPAGGGFKENDETIASGYFALEDLPELSEDKGSREQVEMCFKA 193
Cdd:cd18889   81 FVLCELLGGEFQPNIETIESGYFSLDELPPLSEEKNTKEQIEMCFEA 127

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: 173.52 E-value: 4.74e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  67 PKIGTRAAIFKDNKMLLVQE-SDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHYKGMYPYGIST 145
Cdd:cd04672    1 PKVDVRAAVFKDGKILLVREkSDGRWTLPGGWADVGLSPAENAVKEVREESGYEVRARKLLAVFDRNKGGHPPSPFHVYK 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 499475414 146 VFFLCKPAGGGFKENDETIASGYFALEDLPELSEDKGSREQVEMCFKA 193
Cdd:cd04672   81 LFFLCELIGGEAQTSIETSEVGFFALDDLPPLSLGRVTPEQIERLFEH 128

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: 125.97 E-value: 2.40e-37

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  67 PKIGTRAAIFKDNKMLLVQES-DGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHYKGMYPYGIST 145
Cdd:cd18891    1 PKVDVRAFIQNENKVLLVQDKhTKEWALPGGFAEVGLSPKENILKEVKEETGLHVEVERLLAVFDTDLRQDIPQSFQYYK 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 499475414 146 VFFLCKPAGGGFKENDETIASGYFALEDLPELSEDKGSREQVEMCFK 192
Cdd:cd18891   81 FIFACKILDGEFQENSETSDLQYFSLDQLPNLSLKRTTKEQLQQLFK 127

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: 125.61 E-value: 3.62e-37

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  67 PKIGTRAAIFKD-NKMLLVQE-SDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHYKGMYPYGIS 144
Cdd:cd18890    1 PKVDIRAVVFNDkEEILLVKEkEDGKWTLPGGWADVGYTPTEVAAKEVEEETGLEVSPKKLLAILDKRKHPHPPQPTYVY 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 499475414 145 TVFFLCKPAGGGFKENDETIASGYFALEDLPELSEDKGSREQVEMCF 191
Cdd:cd18890   81 KLFILCEIEGGELKPSFETGEVRFFSENELPELSTDRVTEEQIKELF 127

Hydrolase of X-linked nucleoside diphosphate N terminal; This family of proteins is found in eukaryotes. Proteins in this family are typically between 847 and 5344 amino acids in length. These enzymes hydrolyse the molecular motif of a nucleoside diphosphate linked to some other moiety, X.

Pssm-ID: 432618 Cd Length: 54 Bit Score: 101.83 E-value: 8.81e-29

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 499475414    4 KLVDWAMRLQSLAQAGLTYGKDSFDLERYQEIRDISAEMMVEKSDLPIEKVKNL 57
Cdd:pfam12535   1 KWLEWAKELQAIAQAGLTYSKDPYDRERYEELREIAAEMLAHHTDLPAEKVKDL 54

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 92.35 E-value: 3.14e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  65 QTPKIGTRAAIF-KDNKMLLVQESD----GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSnkhykgMY 139
Cdd:COG1051    3 KVPKVAVDAVIFrKDGRVLLVRRADepgkGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDH------PD 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 499475414 140 PYGISTVFFLCKPAGGGFKENDETIASGYFALEDLPELSEDKGSREQVE 188
Cdd:COG1051   77 RGHVVSVAFLAEVLSGEPRADDEIDEARWFPLDELPELAFTPADHEILE 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: 467560 [Multi-domain] Cd Length: 137 Bit Score: 73.70 E-value: 6.86e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  68 KIGTRAAIF---------KDNKMLLVQESD-GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHYKg 137
Cdd:cd04677    4 LVGHRPLILvgaaviilnEQGRILLQKRTDtGDWGLPGGAMELGESLEETARREVFEETGLTVEELELLGVYSGKDLYY- 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 499475414 138 MYPYG----ISTVFFLCKPAGGGFK-ENDETIASGYFALEDLPEL 177
Cdd:cd04677   83 TYPNGdevyNVTAVYLVRDVSGELKvDDEESLELRFFSLDELPEN 127

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: 65.50 E-value: 4.48e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  69 IGTRAAIFKD-NKMLLVQESD----GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDsnkHYKGMYPYGI 143
Cdd:cd02883    1 VAVGAVVFDDeGRVLLVRRSDgpgpGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYE---FPDPDEGRHV 77

                         90       100
                 ....*....|....*....|....*...
gi 499475414 144 STVFFLCKPAGG--GFKENDETIASGYF 169
Cdd:cd02883   78 VVLVFLARVVGGepPPLDDEEISEVRWV 105

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: 64.84 E-value: 1.28e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  69 IGTRAAIFKDNKMLLVQE----SDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDS---NKHYKGMYPY 141
Cdd:cd04673    2 VAVGAVVFRDGRVLLVRRgnppDAGLWSFPGGKVELGETLEDAALRELREETGLEAEVVGLLTVVDVierDEAGRVRFHY 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 499475414 142 GIstVFFLCKPAGGGFKENDETIASGYFALEDLPELSEDKGSREQVEM 189
Cdd:cd04673   82 VI--LDFLAEWVSGEPVAGDDALDARWFSLEELDGLPLTPGTRDVLER 127

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: 64.91 E-value: 1.30e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  70 GTRAAIFKDN-KMLLVQESD-GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSnkhykGM--YPYGIST 145
Cdd:cd18879   20 GVTAVVLRDAgRVLLVRRADnGRWTPVTGIVEPGEQPADAAVREVLEETGVDVEVERLASVGAS-----PPvtYPNGDQC 94

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 499475414 146 VF----FLCKPAGGGFKEND-ETIASGYFALEDLPELSED 180
Cdd:cd18879   95 QYldltFRCRPVGGEARVNDdESLEVGWFPVDALPPMLPR 134

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: 63.80 E-value: 2.34e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  68 KIGTRAAIFKDNKMLLVQES---DGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLiaIHDSNKHYKGmyPYGIS 144
Cdd:cd04699    2 PVSVKGVIFDNGRVLLLRRSragAGEWELPGGRLEPGESPEEALKREVKEETGLDVSVGEL--LDTWTFELDP--DKGVF 77

                         90       100       110
                 ....*....|....*....|....*....|...
gi 499475414 145 TVFFLCKPAGGGFKENDETIASGYFALEDLPEL 177
Cdd:cd04699   78 IVTYLCRLVGGEVTLSDEHEEYEWVTPEELAEL 110

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: 60.62 E-value: 3.79e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  69 IGTRAAIFKDNKMLLVQESDG---LWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAI---HDSNKHYKGMYpyg 142
Cdd:cd18880    2 IRAKAIIIEDGKLLLVKHRDEggiFYILPGGGQEHGETLPEALKRECLEETGLDVEVGDLLFVreyIGPNKPVHQVE--- 78

                         90
                 ....*....|...
gi 499475414 143 istVFFLCKPAGG 155
Cdd:cd18880   79 ---LFFLCTLEGG 88

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: 60.39 E-value: 4.38e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  77 KDNKMLLVQES----DGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDsnkhykGMYPYGIST--VFFLC 150
Cdd:cd04691   10 KEGKVLLVKRAygpgKGRWTLPGGFVEEGETLDEAIVREVLEETGIDAKPVGIIGVRS------GVIRDGKSDnyVVFLL 83

                         90       100
                 ....*....|....*....|....*
gi 499475414 151 KPAGGGFK-ENDETIASGYFALEDL 174
Cdd:cd04691   84 EYVGGEPKpDERENSEAGFLTLEEA 108

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: 58.47 E-value: 2.95e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  67 PKIGTRAAIFKDNKMLLVQ-----ESdGLWSIPGG---WCEinlSVKENVIKEIKEEAGIDITVEKLIAI-----HDSNK 133
Cdd:cd04679    1 PRVGCGAAILDDGRLLLVLrlrapEA-GHWGLPGGkvdWLE---TVEDAVRREILEELGLEIELTRLLCVvdqidAADGE 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 499475414 134 HYkgmypygISTVFFLCKPAGGGFKENDETIAS-GYFALEDLPE 176
Cdd:cd04679   77 HW-------VAPVYLAEIFSGEPRLMEPEKHGGiGWFALDALPQ 113

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: 54.95 E-value: 5.55e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  69 IGTRAAIF-KDNKMLLVQES--DGlWSIPGGWCEINLSVKENVIKEIKEEAGIDIT-VEKLIAIHdSNKHYKGmypyGIS 144
Cdd:cd04680    1 LGVRAIVLdDAGRVLLVRHTyvPG-WYLPGGGVDKGETAEEAARRELREEAGVVLTgPPRLFGVY-FNRRVSP----RDH 74

                         90       100       110
                 ....*....|....*....|....*....|....
gi 499475414 145 TVFFLCK--PAGGGFKENDETIASGYFALEDLPE 176
Cdd:cd04680   75 VALYRVRefEQTEPPEPNGEIAEAGFFALDALPE 108

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

Pssm-ID: 467570 [Multi-domain] Cd Length: 130 Bit Score: 54.09 E-value: 1.10e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  72 RAA--IFKDNKMLLVQ-ESDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHYKGMYPYGISTVfF 148
Cdd:cd04688    4 RVAaiIIRDGKVLLARgEDDDYYRLPGGRVEFGETSEDALVREFKEELGVEVEVVRLLFVVENFFTYDGKPFHEIGFY-Y 82

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 499475414 149 LCKPAGG--------GFKENDETIASGYFALEDLPEL 177
Cdd:cd04688   83 LVELSDEalyeqdifFLEEDGEKLEFRWIPLEELDEI 119

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: 54.72 E-value: 1.11e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  65 QTPKIGtrAAIF-KDNKMLLVQESD-GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHdSNKHYKGMYPYG 142
Cdd:cd04676   16 FTPSVA--AVILnEDGRILLQRKGGlGLWSLPAGAIEPGEHPAEAVIREVREETGLLVKPTRLLGVF-GGKEFRYTYPNG 92

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 499475414 143 IS---TVF-FLCKPAGGGFKE-NDETIASGYFALEDLPELS 178
Cdd:cd04676   93 DQveyTVIaFKCVVTGGTLNAiDGETSELRYFSRTQMPTLA 133

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: 54.27 E-value: 1.28e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  74 AIFKDNKMLLVQESD-----GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHY-KGMYPYgisTVF 147
Cdd:COG0494   20 LLDDDGRVLLVRRYRygvgpGLWEFPGGKIEPGESPEEAALRELREETGLTAEDLELLGELPSPGYTdEKVHVF---LAR 96

                         90       100       110
                 ....*....|....*....|....*....|
gi 499475414 148 FLCKPAGGGFKENDETIASGYFALEDLPEL 177
Cdd:COG0494   97 GLGPGEEVGLDDEDEFIEVRWVPLDEALAL 126

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 52.49 E-value: 5.38e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414   78 DNKMLLVQESD----GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHYKGMYPYGIS-TVFFLCKP 152
Cdd:pfam00293  14 KGRVLLVRRSKkpfpGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRFPDEHEiLYVFLAEV 93

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 499475414  153 AGGGF-KENDETIASGYFALEDLPELSEDKGSREQVE 188
Cdd:pfam00293  94 EGELEpDPDGEVEEVRWVPLEELLLLKLAPGDRKLLP 130

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: 52.18 E-value: 6.03e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  67 PKIGTRAAIFKD-NKMLLVQ----ESDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDS-----NKHYk 136
Cdd:cd04678    1 PRVGVGVIVLNDdGKVLLGRrkgsHGAGTWALPGGHLEFGESFEECAAREVLEETGLEIRNVRFLTVTNDvfeeeGKHY- 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 499475414 137 gmypygiSTVFFLCKPAGGGFKENDE--TIAS-GYFALEDLPELS 178
Cdd:cd04678   80 -------VTIFVLAEVDDGEPEENMEpdKCEGwEWFSWDELPPLR 117

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: 51.00 E-value: 1.86e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  77 KDNKMLLVQE---SDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAI---HDsnkhykgmYPYGISTVFFLC 150
Cdd:cd04670   12 ENNEVLVVQEkygGPGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFrhqHP--------GRFGKSDLYFVC 83


                 .
gi 499475414 151 K 151
Cdd:cd04670   84 R 84

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

Pssm-ID: 467545 [Multi-domain] Cd Length: 123 Bit Score: 50.65 E-value: 2.16e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  67 PKIGTRAAIFKDNKMLL----VQESDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDsnkhykgmYPYg 142
Cdd:cd04511    1 PKIVVGCLPEWEGKVLLcrraIEPRKGYWTLPAGFMELGETTEQGAARETREEAGARVEIGSLYAVYS--------LPH- 71

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 499475414 143 ISTV--FFLCKPAGGGFKENDETIASGYFALEDLP 175
Cdd:cd04511   72 ISQVyiIFRARLLSPDFSPGPESLEVRLFDEEEIP 106

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

Pssm-ID: 467586 [Multi-domain] Cd Length: 125 Bit Score: 49.59 E-value: 5.10e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  78 DNKMLLVQES--DGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDS--NKHYKGmyPYGISTVFFLCKPA 153
Cdd:cd18874   13 DGKVLLVRSHkwNDLYGIPGGKVEWGETLEEALKREVKEETGLDITDIRFILVQESinSEEFHK--PAHFVFVDYLARTD 90


                 ....*....
gi 499475414 154 GGGFKENDE 162
Cdd:cd18874   91 SSEVVLNEE 99

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: 49.62 E-value: 5.91e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  75 IFKDNKMLLVQESD----GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHYkgmYPYGistvfFLC 150
Cdd:cd04671    8 INEQGEVLMIQEAKrscrGKWYLPAGRVEPGESIVEAAKREVKEETGLKCEPSTLLSVEEAGGSW---YRFV-----FTG 79


                 ....*...
gi 499475414 151 KPAGGGFK 158
Cdd:cd04671   80 NITGGKLK 87

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: 48.60 E-value: 1.18e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  73 AAIFKDNKMLLVQESD-----GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDsnkhykgmYPYGISTV- 146
Cdd:cd03425    6 AIIVDDGRVLIAQRPEgkhlaGLWEFPGGKVEPGETPEQALVRELREELGIEVEVGEPLGTVE--------HDYPDFHVr 77

                         90
                 ....*....|.
gi 499475414 147 --FFLCKPAGG 155
Cdd:cd03425   78 lhVYLCTLWSG 88

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

Pssm-ID: 182536 [Multi-domain] Cd Length: 135 Bit Score: 45.89 E-value: 1.54e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 499475414  73 AAIFKDNKMLLVQ---ESD--GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIH 129
Cdd:PRK10546   9 AIIERDGKILLAQrpaHSDqaGLWEFAGGKVEPGESQPQALIRELREELGIEATVGEYVASH 70

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: 44.90 E-value: 3.00e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  75 IFKDNKMLLVQES-----DGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHYKGMYPYgiSTVFFL 149
Cdd:cd04683    7 LVRGDEVLLLRRAntgydDGWWHLPAGHVEAGETVRAAAVREAKEELGVEIDPEDLRLVHTMHRRSDGGRER--IDFFFR 84

                         90       100
                 ....*....|....*....|....*....
gi 499475414 150 CKPAGG--GFKENDETIASGYFALEDLPE 176
Cdd:cd04683   85 ATRWSGepRNREPDKCAELRWFPLDALPE 113

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: 44.59 E-value: 4.23e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  77 KDNKMLLVQES------DGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVE---KLIAIhdsnkhYKGMYPYGIST-- 145
Cdd:cd04694   12 SDDRVLLTRRAkhmrtfPGVWVPPGGHVELGESLLEAGLRELQEETGLEVSDIqslSLLGL------WESVYPTLLSIgl 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 499475414 146 -------VFFLCKPAGGGFKEN------DETIASGYFALEDLPELSEDKG 182
Cdd:cd04694   86 pkrhhivVYYLVKLSESHENQEqlklqeDEVDAAVWLPKSLLAKLLEAED 135

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: 43.33 E-value: 1.03e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  75 IFKDNKMLLVQE----SDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHYKGMyPYGISTVFFLC 150
Cdd:cd04681   13 IRNEGEILFVRRakepGKGKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYLCSLPNTYLYKGI-TYKTCDLFFTA 91

                         90       100
                 ....*....|....*....|....*..
gi 499475414 151 KPAGGG--FKENDETIASGYFALEDLP 175
Cdd:cd04681   92 ELDEKPklKKAEDEVAELEWLDLEEIE 118

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: 43.05 E-value: 1.21e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 499475414  69 IGTRAAIFKDNKMLLVQESDG----LWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHD 130
Cdd:cd04686    2 FGVYGIIIRNDKLLLIRKTRGpyqgRYDLPGGSQEFGESLEDALKREFAEETGMTVTSYDNLGVYD 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: 467542 [Multi-domain] Cd Length: 130 Bit Score: 42.63 E-value: 1.66e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  89 GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITV--EKLIAIHDSNKHYKGMYPYG-----ISTVFFLCKPAGGGFKEND 161
Cdd:cd03674   25 GRWLQPGGHVEPDEDPLEAALREAREETGLDVELlsPLSPDPLDIDVHPIPANPGEpahlhLDVRYLAVADGDEALRKSD 104

                         90
                 ....*....|....*..
gi 499475414 162 ETIASGYFALEDLPELS 178
Cdd:cd03674  105 ESSDVRWFPLDELEELS 121

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: 42.53 E-value: 1.93e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  73 AAIF----KDNKMLLVQESD----GLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSnkhyKGMYPYG-- 142
Cdd:cd18873    7 CVIFgfddGELKVLLIKRKNepfkGGWALPGGFVREDETLEDAARRELREETGLKDIYLEQLGTFGD----PDRDPRGrv 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 499475414 143 ISTVFF-LCKPAGGGFKENDETIASGYFALED-LPELSED 180
Cdd:cd18873   83 ISVAYLaLVPEEDLAPKAGDDAAEARWFPVDElLPPLAFD 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: 467594 Cd Length: 136 Bit Score: 41.68 E-value: 4.70e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 499475414  72 RAAIFKDNKMLLVQ-ESDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLI 126
Cdd:cd18883    4 RGVIISDEHLLLARvKGDDKTFLPGGHIEIGESAEIALVRELREELGLSCKVGRYL 59

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: 41.05 E-value: 9.42e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  79 NKMLLVQE--------SDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIhdsnkhYKGMYPYGISTV--FF 148
Cdd:cd04700   25 GDILLVQEkgisghpeKAGLWHIPSGAVEDGENPQDAAVREACEETGLRVRLVKFLGA------YLGRFPDGVLVLrhVW 98

                         90       100       110
                 ....*....|....*....|....*....|..
gi 499475414 149 LCKPAGGGF---KENDETIASGYFALEDLPEL 177
Cdd:cd04700   99 LAEPEPGQVlapAFTDEIAEASFVSREEFAQL 130

nudix hydrolase

Pssm-ID: 215184 [Multi-domain] Cd Length: 144 Bit Score: 40.61 E-value: 1.28e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 499475414  60 NEVGYQTPKIGTRAAIFKDNKMLLVQE----SDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAI 128
Cdd:PLN02325   1 METGEPIPRVAVVVFLLKGNSVLLGRRrssiGDSTFALPGGHLEFGESFEECAAREVKEETGLEIEKIELLTV 73

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: 39.19 E-value: 2.23e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  72 RAAIF--KDNKMLLVQESDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNK--HYkgmypygistVF 147
Cdd:cd04667    2 RATVIcrRGDRILLVARRGGRWLLPGGKIEPGESPLEAAIRELKEETGLAALSLLYLFEHEGPHklHH----------VF 71

                         90       100       110
                 ....*....|....*....|....*....|.
gi 499475414 148 FLCKPAGGGFKENDETIASGYFALEDLPELS 178
Cdd:cd04667   72 LAEAPDGGRPRPGNEIARCRWVSADQLRDLN 102

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: 39.01 E-value: 3.34e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  73 AAIFKDNKMLLVQES---DGLWSIPGGWCEINLSVKENVIKEIKEEAGIDItvekliaihdSNKHYKGMYPYGIST---V 146
Cdd:cd03429    7 LVTNGEDKILLARQPrwpPGRYSLLAGFVEPGETLEEAVRREVKEEVGLRV----------KNVRYVGSQPWPFPSslmL 76

                         90       100       110
                 ....*....|....*....|....*....|..
gi 499475414 147 FFLCKPAGGGFK-ENDETIASGYFALEDLPEL 177
Cdd:cd03429   77 GFTAEADSGEITvDDDELEDARWFSRDELPEA 108

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: 38.66 E-value: 4.79e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 499475414  71 TRAA-IFKDNKMLLVQESDG---LWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIHDSNKHYKG 137
Cdd:cd03675    2 TVAAvVERDGRFLLVEEETDgrlVLNQPAGHLEPGESLLEAAIRETLEETGWEVEPTALLGIYQWTAPDNG 72

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: 38.37 E-value: 6.66e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  75 IFKDNKMLLV----QESDGLWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAI-----HDSNKHYkGMYpygist 145
Cdd:cd18886    7 IIRDDEVLLLnrnkKPNMGKWNGVGGKLEPGESPEECAIREVFEETGLELEDLQLRGIvtfpsFDGGEDW-LMY------ 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 499475414 146 VFFLCKPAGGGFKENDETIASgYFALEDLPELSEDKGSREQVEMCFKAYRDSH 198
Cdd:cd18886   80 VFLAEAFSGELVESDREGILA-WVPIDWLLNLPLWEGDRYFLPLLFDNEPPFE 131

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: 37.57 E-value: 8.94e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 499475414  73 AAIFKD--NKMLLVQES--DGlWSIPGGWCEINLSVKENVIKEIKEEAGIDITVEKLIAIH 129
Cdd:cd18876    4 GALFTDaaGRVLLVKPTykDG-WELPGGVVEAGESPLQAARREVREELGLDVPVGRLLAVD 63

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: 36.33 E-value: 2.90e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  74 AIFKDNKMLLVQE-----SDGLWSIPGGWCEINLSVKENVIKEIKEEAGidITVEKLIaihdsnkHYKGMYPY-GIST-- 145
Cdd:cd03424    9 AITDDGKVVLVRQyrhpvGRVLLELPAGKIDPGEDPEEAARRELEEETG--YTAGDLE-------LLGSFYPSpGFSDer 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 499475414 146 -VFFLCK---PAGGGFKENDETIASGYFALEDLPELSEDK 181
Cdd:cd03424   80 iHLFLAEdltPVSEQALDEDEFIEVVLVPLEEALEMIEDG 119

dihydroneopterin triphosphate pyrophosphatase; Provisional

Pssm-ID: 236516 [Multi-domain] Cd Length: 148 Bit Score: 36.41 E-value: 3.96e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499475414  77 KDNKMLLVQESD--GLW-SIPGGwCEINLSVKENVIKEIKEEAGIDITVEK--LIAIHDSNK-----HYKGMYPYGIS-- 144
Cdd:PRK09438  17 PDLGVLMLQRADdpDFWqSVTGS-LEEGETPAQTAIREVKEETGIDVLAEQltLIDCQRSIEyeifpHWRHRYAPGVTrn 95

                         90
                 ....*....|.
gi 499475414 145 --TVFFLCKPA 153
Cdd:PRK09438  96 teHWFCLALPH 106