NCBI Conserved Domain Search

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: 94.61 E-value: 1.37e-25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  42 AIIEHDGRVLALR--QAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAT---DFDPEIRHVDVIFRVVCD 116
Cdd:cd04699    7 GVIFDNGRVLLLRrsRAGAGEWELPGGRLEPGESPEEALKREVKEETGLDVSVGELLDTwtfELDPDKGVFIVTYLCRLV 86

                         90       100
                 ....*....|....*....|...
gi 308435615 117 ERpEVEVASEALESGWFALDELP 139
Cdd:cd04699   87 GG-EVTLSDEHEEYEWVTPEELA 108

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 90.81 E-value: 4.21e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  32 MQPTFSAGAVAIIEH-DGRVLALRQAHRSG---WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAT-DFDPEIRH 106
Cdd:COG1051    1 MTKVPKVAVDAVIFRkDGRVLLVRRADEPGkglWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVfDHPDRGHV 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 308435615 107 VDVIFRVVCDErPEVEVASEALESGWFALDELP 139
Cdd:COG1051   81 VSVAFLAEVLS-GEPRADDEIDEARWFPLDELP 112

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: 82.63 E-value: 1.06e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  33 QPTFSAGAVAIIEHD-GRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDFDPEIRH----- 106
Cdd:cd18879   14 DPLWLPGVTAVVLRDaGRVLLVRRADNGRWTPVTGIVEPGEQPADAAVREVLEETGVDVEVERLASVGASPPVTYpngdq 93

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 308435615 107 ---VDVIFR--------VVCDErpevevasEALESGWFALDELPHPD-KSTRRIQRA 151
Cdd:cd18879   94 cqyLDLTFRcrpvggeaRVNDD--------ESLEVGWFPVDALPPMLpRFRRRIALA 142

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: 80.30 E-value: 5.52e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  42 AIIEhDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATD------FDPEIRHVDVIFrVVC 115
Cdd:cd04672    8 AVFK-DGKILLVREKSDGRWTLPGGWADVGLSPAENAVKEVREESGYEVRARKLLAVFdrnkggHPPSPFHVYKLF-FLC 85

                         90       100       110
                 ....*....|....*....|....*....|....
gi 308435615 116 DER-PEVEVASEALESGWFALDELPHPdkSTRRI 148
Cdd:cd04672   86 ELIgGEAQTSIETSEVGFFALDDLPPL--SLGRV 117

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: 78.60 E-value: 1.80e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  38 AGAVAIIEHDGRVLALRQAHRS---GWSLPGGLIDAGEQPQDAVVREVREETGLDIEP----GSVMATDFDPEIRHVDVI 110
Cdd:cd02883    2 AVGAVVFDDEGRVLLVRRSDGPgpgGWELPGGGVEPGETPEEAAVREVREETGLDVEVlrllGVYEFPDPDEGRHVVVLV 81

                         90       100
                 ....*....|....*....|....
gi 308435615 111 FRVVCDER-PEVEVASEALESGWF 133
Cdd:cd02883   82 FLARVVGGePPPLDDEEISEVRWV 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: 76.78 E-value: 1.32e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  38 AGAVAIIEHDGRVLALRQA---HRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGS------VMATDFDPEIRHVD 108
Cdd:cd04673    2 VAVGAVVFRDGRVLLVRRGnppDAGLWSFPGGKVELGETLEDAALRELREETGLEAEVVGlltvvdVIERDEAGRVRFHY 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 308435615 109 VIFRVVCDE-RPEVEVASEALESGWFALDELPHPD--KSTRRIQRAV 152
Cdd:cd04673   82 VILDFLAEWvSGEPVAGDDALDARWFSLEELDGLPltPGTRDVLERA 128

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: 75.68 E-value: 3.89e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  40 AVAIIEHDGRVLALR--QAHRSG-WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAT---DFDPEIRH-VDVIFR 112
Cdd:cd04678    6 GVIVLNDDGKVLLGRrkGSHGAGtWALPGGHLEFGESFEECAAREVLEETGLEIRNVRFLTVtndVFEEEGKHyVTIFVL 85

                         90       100       110
                 ....*....|....*....|....*....|...
gi 308435615 113 V-VCDERPEVEVASEALES-GWFALDELPHPDK 143
Cdd:cd04678   86 AeVDDGEPEENMEPDKCEGwEWFSWDELPPLRP 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: 467559 [Multi-domain] Cd Length: 144 Bit Score: 75.90 E-value: 4.70e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  40 AVAIIEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDFDPEIR----------HVDV 109
Cdd:cd04676   21 AAVILNEDGRILLQRKGGLGLWSLPAGAIEPGEHPAEAVIREVREETGLLVKPTRLLGVFGGKEFRytypngdqveYTVI 100

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 308435615 110 IFRVVCDERPEVEVASEALESGWFALDE-----LPHPDKS 144
Cdd:cd04676  101 AFKCVVTGGTLNAIDGETSELRYFSRTQmptlaLPYPDEI 140

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: 74.41 E-value: 8.82e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  40 AVAIIEHDGRVL-ALRQAHRS---GWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGS-VMATDFDPEIRHVDVIFRVV 114
Cdd:cd03425    4 VAAIIVDDGRVLiAQRPEGKHlagLWEFPGGKVEPGETPEQALVRELREELGIEVEVGEpLGTVEHDYPDFHVRLHVYLC 83

                         90       100
                 ....*....|....*....|....*
gi 308435615 115 CDERPEVEvASEALESGWFALDELP 139
Cdd:cd03425   84 TLWSGEPQ-LLEHQELRWVTPEELD 107

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: 73.87 E-value: 1.65e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  39 GAVAIIEHDGRVLALRQAHRSG---WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDFDP---EIRHVDVIFR 112
Cdd:cd04691    3 GVGGVVVKEGKVLLVKRAYGPGkgrWTLPGGFVEEGETLDEAIVREVLEETGIDAKPVGIIGVRSGVirdGKSDNYVVFL 82

                         90       100
                 ....*....|....*....|....*..
gi 308435615 113 V-VCDERPEVEvASEALESGWFALDEL 138
Cdd:cd04691   83 LeYVGGEPKPD-ERENSEAGFLTLEEA 108

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 73.67 E-value: 2.23e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615   40 AVAIIEHDGRVLALRQA---HRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMA--------TDFDPEIRHVD 108
Cdd:pfam00293   7 GVVLLNEKGRVLLVRRSkkpFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGslhylapfDGRFPDEHEIL 86

                          90       100       110
                  ....*....|....*....|....*....|....
gi 308435615  109 VIFRVVCDERPEVEVASEALESGWFALDELPHPD 142
Cdd:pfam00293  87 YVFLAEVEGELEPDPDGEVEEVRWVPLEELLLLK 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: 467542 [Multi-domain] Cd Length: 130 Bit Score: 73.45 E-value: 2.48e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  36 FSAGAVAIIEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEP-GSVMATDFD------------P 102
Cdd:cd03674    2 FTASAFVVNPDRGKVLLVHHRKLGRWLQPGGHVEPDEDPLEAALREAREETGLDVELlSPLSPDPLDidvhpipanpgeP 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 308435615 103 EIRHVDVIFRVVCDERPEVEVASEALESGWFALDELPHPDkSTRRIQRAV 152
Cdd:cd03674   82 AHLHLDVRYLAVADGDEALRKSDESSDVRWFPLDELEELS-MDPNLRKLL 130

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: 2.63e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  33 QPTFSAGAVAIIEHD-GRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDFDPEIRH----- 106
Cdd:cd04677    8 RPLILVGAAVIILNEqGRILLQKRTDTGDWGLPGGAMELGESLEETARREVFEETGLTVEELELLGVYSGKDLYYtypng 87

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 308435615 107 -----VDVIFrVVCDERPEVEVA-SEALESGWFALDELP 139
Cdd:cd04677   88 devynVTAVY-LVRDVSGELKVDdEESLELRFFSLDELP 125

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: 73.34 E-value: 3.54e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  38 AGAVaIIEHDGRVLAL--RQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAtdfdpeIRHV-DVIFR-- 112
Cdd:cd04670    5 VGGL-VINENNEVLVVqeKYGGPGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILG------FRHQhPGRFGks 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 308435615 113 ---VVCDERPEVEVA-----SEALESGWFALDEL---PHPDKSTRRIQRAVR 153
Cdd:cd04670   78 dlyFVCRLRPLSDEEikicpEEIAEAKWMPLEEYlkqPNVSQINKLVAKLLL 129

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

Pssm-ID: 440260 [Multi-domain] Cd Length: 143 Bit Score: 73.14 E-value: 5.57e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  38 AGAVAIIEHDGRVLALRQA----HRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEP----GSVMATDFDPEIRHVDV 109
Cdd:COG0494   15 AVVVVLLDDDGRVLLVRRYrygvGPGLWEFPGGKIEPGESPEEAALRELREETGLTAEDlellGELPSPGYTDEKVHVFL 94

                         90       100       110
                 ....*....|....*....|....*....|
gi 308435615 110 IFRVVCDERPEVEVASEALESGWFALDELP 139
Cdd:COG0494   95 ARGLGPGEEVGLDDEDEFIEVRWVPLDEAL 124

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: 69.95 E-value: 6.31e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  42 AIIeHDGRVLALRQahRSG-WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAT------DFDPEIRHVDVIFrVV 114
Cdd:cd18889    8 AIF-KDDKILLVQE--KDGrWSLPGGWVDVNQSIKENTIKEAKEEAGLDVEPKRIIAVldrnkhNKPPYAYGIYKIF-VL 83

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 308435615 115 CD-ERPEVEVASEALESGWFALDELP--HPDKSTR 146
Cdd:cd18889   84 CElLGGEFQPNIETIESGYFSLDELPplSEEKNTK 118

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

Pssm-ID: 467591 [Multi-domain] Cd Length: 126 Bit Score: 69.48 E-value: 8.25e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  42 AIIEHDGRVLALRQAHRSG--WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMA-TDF---DPEIRHVDVIFRVvc 115
Cdd:cd18880    6 AIIIEDGKLLLVKHRDEGGifYILPGGGQEHGETLPEALKRECLEETGLDVEVGDLLFvREYigpNKPVHQVELFFLC-- 83

                         90       100       110
                 ....*....|....*....|....*....|...
gi 308435615 116 derpEVEVASEALES---------GWFALDELP 139
Cdd:cd18880   84 ----TLEGGELTLGSdpdlnqvgvEWIPLEELD 112

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: 69.50 E-value: 8.48e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  40 AVAIIEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAT-----DFDPEIRH-VDVIFRV 113
Cdd:cd04688    5 VAAIIIRDGKVLLARGEDDDYYRLPGGRVEFGETSEDALVREFKEELGVEVEVVRLLFVvenffTYDGKPFHeIGFYYLV 84

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 308435615 114 -------VCDERPEVEVASEALESGWFALDELPHPD 142
Cdd:cd04688   85 elsdealYEQDIFFLEEDGEKLEFRWIPLEELDEID 120

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: 68.87 E-value: 1.59e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  38 AGAVAIIEHDGRVL---ALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAT--DFDPEIRH--VDVI 110
Cdd:cd04679    3 VGCGAAILDDGRLLlvlRLRAPEAGHWGLPGGKVDWLETVEDAVRREILEELGLEIELTRLLCVvdQIDAADGEhwVAPV 82

                         90       100       110
                 ....*....|....*....|....*....|..
gi 308435615 111 FRVVCDERPEVEVASEALES-GWFALDELPHP 141
Cdd:cd04679   83 YLAEIFSGEPRLMEPEKHGGiGWFALDALPQP 114

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

Pssm-ID: 467572 [Multi-domain] Cd Length: 123 Bit Score: 67.95 E-value: 2.89e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  40 AVAIIEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVM-------ATDFDPEIRHVDVIFR 112
Cdd:cd04690    4 AAVIIIKDGRLLLVRKRGTDAFYLPGGKREPGETPLQALVRELKEELGLDLDPDSLRflgtfeaPAANEPGTTVRMTCFT 83

                         90       100       110
                 ....*....|....*....|....*....|
gi 308435615 113 VVCDErpEVEVASEALESGWFALDELPHPD 142
Cdd:cd04690   84 ADYDG--EPQPAAEIEELRWLDPADPDDDR 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: 467564 [Multi-domain] Cd Length: 135 Bit Score: 67.98 E-value: 4.58e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  37 SAGAVAIIEHDGRVLALRQAHRSG---WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAT--------DFDpeIR 105
Cdd:cd04681    6 AAAVGVIIRNEGEILFVRRAKEPGkgkLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYLCSlpntylykGIT--YK 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 308435615 106 HVDVIFRVVCDERPEVEVA-SEALESGWFALDELPhPDK----STRR 147
Cdd:cd04681   84 TCDLFFTAELDEKPKLKKAeDEVAELEWLDLEEIE-PEKlafpSIRK 129

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: 66.84 E-value: 8.05e-15

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 308435615  47 DGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDFDP 102
Cdd:cd18876   11 AGRVLLVKPTYKDGWELPGGVVEAGESPLQAARREVREELGLDVPVGRLLAVDWVP 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: 467563 [Multi-domain] Cd Length: 121 Bit Score: 62.65 E-value: 2.97e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  41 VAIIEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDFDPEIRHVD--VIFRVVCDER 118
Cdd:cd04680    5 AIVLDDAGRVLLVRHTYVPGWYLPGGGVDKGETAEEAARRELREEAGVVLTGPPRLFGVYFNRRVSPRdhVALYRVREFE 84

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 308435615 119 PEVEVAS--EALESGWFALDELPhPDKST---RRIQ 149
Cdd:cd04680   85 QTEPPEPngEIAEAGFFALDALP-EDTTPatrRRLA 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: 467545 [Multi-domain] Cd Length: 123 Bit Score: 62.21 E-value: 4.48e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  42 AIIEHDGRVLALRQA--HRSG-WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDFDPEIRHVDVIFRVVCdER 118
Cdd:cd04511    7 CLPEWEGKVLLCRRAiePRKGyWTLPAGFMELGETTEQGAARETREEAGARVEIGSLYAVYSLPHISQVYIIFRARL-LS 85

                         90       100
                 ....*....|....*....|.
gi 308435615 119 PEVEVASEALESGWFALDELP 139
Cdd:cd04511   86 PDFSPGPESLEVRLFDEEEIP 106

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: 62.03 E-value: 6.59e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  42 AIIEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATdFDPEiRHVDVI-------FRVV 114
Cdd:cd18891    7 AFIQNENKVLLVQDKHTKEWALPGGFAEVGLSPKENILKEVKEETGLHVEVERLLAV-FDTD-LRQDIPqsfqyykFIFA 84

                         90       100
                 ....*....|....*....|....*.
gi 308435615 115 CD-ERPEVEVASEALESGWFALDELP 139
Cdd:cd18891   85 CKiLDGEFQENSETSDLQYFSLDQLP 110

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: 61.67 E-value: 8.88e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  42 AIIEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAT------DFDPEIRHVDVIFrVVC 115
Cdd:cd18890    8 VVFNDKEEILLVKEKEDGKWTLPGGWADVGYTPTEVAAKEVEEETGLEVSPKKLLAIldkrkhPHPPQPTYVYKLF-ILC 86

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 308435615 116 D-ERPEVEVASEALESGWFALDELphPDKSTRRIQR 150
Cdd:cd18890   87 EiEGGELKPSFETGEVRFFSENEL--PELSTDRVTE 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: 467568 [Multi-domain] Cd Length: 138 Bit Score: 61.43 E-value: 1.17e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  41 VAIIEHDGRVLALRQAHRSG-----WSLPGGLIDAGEQPQDAVVREVREETGLDIEP----GSVMATD----FDPEIRHV 107
Cdd:cd04685    5 VLLLDPDGRVLLFRFHDPDDpgrswWFTPGGGVEPGESPEQAAVRELREETGLRLEPddlgGPVWRRRavfdFSGETVRQ 84

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 308435615 108 DVIFRVVCDERPEVEVASEA-------LESGWFALDEL 138
Cdd:cd04685   85 DERFFLVRVPAFEVDTAGWTdleraviDGHRWWSLAEL 122

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: 61.82 E-value: 1.24e-12

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 308435615  43 IIEHDGRVLAL-RQ-AHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIE 91
Cdd:cd18875    9 IYDGEDRVLVLdRVkKDWGGYTFPGGHVEPGESFVDSVIREVKEETGLTIK 59

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: 61.03 E-value: 1.74e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  36 FSAGAVAIIEHDG--RVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEpgsvmatDFDPEIRHV------ 107
Cdd:cd03428    3 KSAGAIIYRRDNGeiEFLLLQHSYGGHWDFPKGHVEPGESELETALRETKEETGLTVD-------DLPPGFRETltysfk 75

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 308435615 108 -----DVIF---RVVCDErpEVEVASEALESGWFALDE 137
Cdd:cd03428   76 egvekTVVYflaELTPDV--EVKLSEEHQDYKWLPYEE 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: 467569 [Multi-domain] Cd Length: 130 Bit Score: 60.77 E-value: 2.03e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  39 GAVAIIEHDGRVLALRQ-----AHRsgWSLPGGLIDAGEQPQDAVVREVREETGLDIEP-GSVMATDFDPE--------I 104
Cdd:cd04686    3 GVYGIIIRNDKLLLIRKtrgpyQGR--YDLPGGSQEFGESLEDALKREFAEETGMTVTSyDNLGVYDFFVPwsdkelgdV 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 308435615 105 RHVDVIFRV-VCDERPEVEV---ASEALESGWFALDELP 139
Cdd:cd04686   81 HHIGVFYDVeLLDNNISELLqfeGQDSLGAVWIPLQDLT 119

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: 59.81 E-value: 4.67e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  41 VAIIEHDGRVLALRQAHRSG--WSLPGGLIDAGEQPQDAVVREVREETGLDIE------------PGSVMatdfdpeirh 106
Cdd:cd03429    6 VLVTNGEDKILLARQPRWPPgrYSLLAGFVEPGETLEEAVRREVKEEVGLRVKnvryvgsqpwpfPSSLM---------- 75

                         90       100       110
                 ....*....|....*....|....*....|...
gi 308435615 107 vdVIFRVVCDERPEVEVASEALESGWFALDELP 139
Cdd:cd03429   76 --LGFTAEADSGEITVDDDELEDARWFSRDELP 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: 59.61 E-value: 4.93e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  34 PTFSAGAVaIIEHDGRVLALRQAHRSG-WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATD---FDPEI---RH 106
Cdd:cd18874    1 PEPTVGAL-IFNPDGKVLLVRSHKWNDlYGIPGGKVEWGETLEEALKREVKEETGLDITDIRFILVQesiNSEEFhkpAH 79

                         90       100       110
                 ....*....|....*....|....*....|..
gi 308435615 107 VdVIFRVVCDERP-EVEVASEALESGWFALDE 137
Cdd:cd18874   80 F-VFVDYLARTDSsEVVLNEEAVEYLWVEPEE 110

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

Pssm-ID: 467593 [Multi-domain] Cd Length: 130 Bit Score: 59.19 E-value: 8.71e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  37 SAGAVAII-EHDGRVL-ALRQAHRS----G-WSLPGGLIDAGEQPQDAVVREVREETGLDI-EPGSVMATDFDPEIRHVD 108
Cdd:cd18882    1 HEVAIAILyDDRGKVLlQLRDDKPGipypGyWGLFGGHLEPGETPEEAIRRELEEEIGYEPgEFRFFLLYTEDDGEDRIR 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 308435615 109 VIFRVVCDERPEVEVASEALESGWFALDELPH 140
Cdd:cd18882   81 HVFHAPLDVDLSDLVLNEGQALRLFSPEEILQ 112

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: 58.29 E-value: 1.78e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  39 GAVAI--IEHDGRVLALRQ----AHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIE-----PGSVMATDFDPEIRHV 107
Cdd:cd03424    3 GAVAVlaITDDGKVVLVRQyrhpVGRVLLELPAGKIDPGEDPEEAARRELEEETGYTAGdlellGSFYPSPGFSDERIHL 82

                         90       100       110
                 ....*....|....*....|....*....|...
gi 308435615 108 dVIFRVVCDERPEVEVASEALESGWFALDELPH 140
Cdd:cd03424   83 -FLAEDLTPVSEQALDEDEFIEVVLVPLEEALE 114

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: 57.25 E-value: 4.80e-11

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 308435615  39 GAVAIIEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGS 94
Cdd:cd04684   17 GAYAVIFNDEGKVLLVQTPNGGYFLPGGGIEPGETPEEALHREVLEETGWEIEIGE 72

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: 56.94 E-value: 5.78e-11

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 308435615  38 AGAVaIIEHDGRVLALRQAHRS---GWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATD 99
Cdd:cd04671    3 VAAV-IINEQGEVLMIQEAKRScrgKWYLPAGRVEPGESIVEAAKREVKEETGLKCEPSTLLSVE 66

bifunctional NMN adenylyltransferase/ADP-ribose pyrophosphatase and similar proteins; Bacterial NadM-Nudix is a bifunctional enzyme containing a nicotinamide mononucleotide (NMN) adenylyltransferase (NMNAT) and an ADP-ribose pyrophosphatase (ADPRase) domain. NMNAT was initially identified as an NAD+ synthase that catalyzes the reversible conversion of NMN to NAD+ in the final step of both the de novo biosynthesis and salvage pathways in most organisms across all three kingdoms of life ADPRase is a member of the NUDIX family proteins, catalyzes the metal-induced and concerted general acid-base hydrolysis of ADP ribose (ADPR) into AMP and ribose-5'-phosphate (R5P). Additional members in this cd include bacterial transcriptional regulator, NrtR, which represses the transcription of NAD biosynthetic genes in vitro and adenosine diphosphate ribose (ADPR), as well as NadQ, a NUDIX-like ATP-responsive regulator of NAD biosynthesis. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belong to this superfamily requires a divalent cation, such as Mg2+ or Mn2+ for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, U=I, L or V) which functions as metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467585 [Multi-domain] Cd Length: 132 Bit Score: 56.78 E-value: 6.70e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  34 PTFSAGAVAIIEHDG--RVLALRQA---HRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAT----DFDPEI 104
Cdd:cd18873    1 PSVTVDCVIFGFDDGelKVLLIKRKnepFKGGWALPGGFVREDETLEDAARRELREETGLKDIYLEQLGTfgdpDRDPRG 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 308435615 105 RHVDVIFRVVCDERPEVEVA-SEALESGWFALDELPHP 141
Cdd:cd18873   81 RVISVAYLALVPEEDLAPKAgDDAAEARWFPVDELLPP 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: 467575 [Multi-domain] Cd Length: 157 Bit Score: 57.15 E-value: 7.20e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  20 LPAGLSHRIVHAmqptfsagavaIIEH-DGRVL-ALRQAHRSGWSL-----PGGLIDAGEQPQDAVVREVREETGLDIEP 92
Cdd:cd04693   23 LPEGEYHLVVHV-----------WIFNsDGEILiQQRSPDKKGFPGmweasTGGSVLAGETSLEAAIRELKEELGIDLDA 91

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: 56.92 E-value: 7.26e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  39 GAVAIIE-HDGRVLALRQAHR-----SGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPG----------SVMATDFD- 101
Cdd:cd04694    4 GVVVLIEdSDDRVLLTRRAKHmrtfpGVWVPPGGHVELGESLLEAGLRELQEETGLEVSDIqslsllglweSVYPTLLSi 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 308435615 102 -PEIRHVDVIF-RVVCDERPEVEVA-----SEALESGWFALDELPH 140
Cdd:cd04694   84 gLPKRHHIVVYyLVKLSESHENQEQlklqeDEVDAAVWLPKSLLAK 129

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: 56.14 E-value: 8.74e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  40 AVAIIEHDGRVLALRQAhRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDFDPEIRHvdVIFRVVCDERP 119
Cdd:cd04667    3 ATVICRRGDRILLVARR-GGRWLLPGGKIEPGESPLEAAIRELKEETGLAALSLLYLFEHEGPHKLH--HVFLAEAPDGG 79

                         90       100       110
                 ....*....|....*....|....*....|.
gi 308435615 120 EVEVASEALESGWFALDELPHPDKS--TRRI 148
Cdd:cd04667   80 RPRPGNEIARCRWVSADQLRDLNLSraTRLI 110

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: 56.81 E-value: 1.00e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 308435615  40 AVAIIEHDGRVLALRQAHRSG-WSLPGGLIDAGEQPQDAVVREVREETGLDIE 91
Cdd:cd03671    7 GIVLFNRDGQVLVGRRIDVPGaWQFPQGGIDEGEDPEEAALRELYEETGLSPE 59

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: 56.02 E-value: 1.41e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  36 FSAGAVAI--IEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPG 93
Cdd:cd03673    2 EAAGGVVWrgRGGGGEVLLIHRPRYDDWSLPKGKLEPGETPEEAAVREVEEETGLRVRLG 61

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: 55.33 E-value: 1.97e-10

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 308435615  40 AVAIIEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETG 87
Cdd:cd04665    3 VVVIARYKGKWLFTRHKERRGWEFPGGKREPGETIEEAARRELYEETG 50

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: 55.33 E-value: 2.39e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  36 FSAGAVAIIEHD-GRVLALRQAHRSG-WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSV----------MATDFDPE 103
Cdd:cd04664    1 FSVLVVIYRKDEeGEVLLLKRTDDGGfWQSVTGGIEDGETPWQAALRELKEETGLDPLELQLidlnvsnfyeIFDDWRPG 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 308435615 104 IRHVDV-IFRVVCDERPEVEVASEALESGWFALDE 137
Cdd:cd04664   81 VTVNTEhVFAVEVPEEQPIRLSPEHTDYRWLPYEE 115

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: 54.10 E-value: 7.79e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  34 PTFsaGAVaIIEHDG-RVLALRQAH-RSGWSLPGGLIDAGEQPQDAVVREVREETGLDIEPGsvMATDFDPE-------- 103
Cdd:cd03672    2 PVR--GAI-LLNEDLdKVLLVKGWKsNSSWGFPKGKINKDESDADCAIREVYEETGFDISDL--INDKDYIEltingqrv 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 308435615 104 ----IRHVDVIFRVVCDERPEV-EVAsealesgWFALDELP 139
Cdd:cd03672   77 rlyiIPGVPEDTPFEPQTRKEIsKIE-------WFDIDDLP 110

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

Pssm-ID: 467558 [Multi-domain] Cd Length: 118 Bit Score: 52.46 E-value: 2.51e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 308435615  40 AVAIIEHDGRVLALRQAHRSG---WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSV 95
Cdd:cd04674    7 VVALLPVRDGLLVIRRGIEPGhgeLALPGGYIEYGETWQEAAVRELREETGVEADAAEV 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: 467595 [Multi-domain] Cd Length: 125 Bit Score: 52.41 E-value: 2.62e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 308435615  42 AIIEHDGRVLAlrqAHRSGW-----SLPGGLIDAGEQPQDAVVREVREETGLD-IEPGSVMATDF 100
Cdd:cd18884   14 AIVEHDGHIVL---ARNKAWpegwyGLVTGFLEAGESPEEAVLREVKEELGLDgHEAKFIGHYAF 75

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 54.63 E-value: 3.32e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  34 PTF-SAGAVAIieHDGRVLALRQAHRSG---WSLPGGLIDAGEQPQDAVVREVREETGLDIEP----GSVMATD-FD--- 101
Cdd:PRK05379 201 PTFvTVDAVVV--QSGHVLLVRRRAEPGkglWALPGGFLEQDETLLDACLRELREETGLKLPEpvlrGSIRDQQvFDhpg 278

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 308435615 102 -----PEIRHVDViFRVVCDERPEVEVASEALESGWFALDEL-PHPDK 143
Cdd:PRK05379 279 rslrgRTITHAFL-FEFPAGELPRVKGGDDADKARWVPLAELlAMRDR 325

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: 52.14 E-value: 4.01e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 308435615  42 AIIEHDGRVLaLRQAHRSG---WSLPGGLIDAGEQPQDAVVREVREETGLDIEP 92
Cdd:cd03675    5 AVVERDGRFL-LVEEETDGrlvLNQPAGHLEPGESLLEAAIRETLEETGWEVEP 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: 467548 [Multi-domain] Cd Length: 132 Bit Score: 51.91 E-value: 4.05e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  40 AVAIIEHDGRVLALRQA--HRSGWSLPGGLIDAGEQPQDAVVREVREETGLD--IEPGSVMATDFDPEIRHVDVIFRV-V 114
Cdd:cd04663    5 AYVTRGRNRELLVFEHPdfPEAGLQVPKGTVEPGESPEEAALRELAEETGLTgaRVVVDLGSHDEGFEELHQRWFFHLcL 84


                 ....*.
gi 308435615 115 CDERPE 120
Cdd:cd04663   85 AGEPPE 90

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

Pssm-ID: 182536 [Multi-domain] Cd Length: 135 Bit Score: 52.05 E-value: 4.49e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 308435615  42 AIIEHDGRVL-ALRQAHRSG---WSLPGGLIDAGE-QPQdAVVREVREETGLDIEPGSVMAT 98
Cdd:PRK10546   9 AIIERDGKILlAQRPAHSDQaglWEFAGGKVEPGEsQPQ-ALIRELREELGIEATVGEYVAS 69

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: 51.59 E-value: 7.06e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  47 DGRVLALRQaHRSGWS-------LPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDFDpeiRHVDVIFRVV---CD 116
Cdd:cd18877   29 DGGPHVLLQ-HRAWWThqggtwaLPGGARDSGETPEAAALRETEEETGLDADTLRVVGTHVD---DHGGWSYTTVlasAP 104

                         90       100
                 ....*....|....*....|....
gi 308435615 117 ERPEVEVAS-EALESGWFALDELP 139
Cdd:cd18877  105 EPLPVRPANeESVELRWVPLDEVE 128

RNA pyrophosphohydrolase; Reviewed

Pssm-ID: 234820 [Multi-domain] Cd Length: 156 Bit Score: 50.54 E-value: 1.97e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 308435615  40 AVAIIEHDGRVLAlrqAHRSG----WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMA 97
Cdd:PRK00714  12 GIILLNRQGQVFW---GRRIGqghsWQFPQGGIDPGETPEQAMYRELYEEVGLRPEDVEILA 70

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: 49.93 E-value: 3.34e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 308435615  41 VAIIEHDGRVLALRQAHRSG---WSLPGGLIDAGEQPQDAVVREVREETGLDIE 91
Cdd:cd18886    4 LCFIIRDDEVLLLNRNKKPNmgkWNGVGGKLEPGESPEECAIREVFEETGLELE 57

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: 49.45 E-value: 3.73e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  64 PGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAT-----DFDPEIRHVDViFRvvCDERPEVEVASEALESGWFALDEL 138
Cdd:cd03427   32 FGGKVEPGETIEEAAVRELEEEAGLTATELEKVGRlkfefPDDPEAMDVHV-FR--ADSWTGEPQETEEMRPQWFDLDDI 108


                 .
gi 308435615 139 P 139
Cdd:cd03427  109 P 109

NAD(+) diphosphatase;

Pssm-ID: 234699 [Multi-domain] Cd Length: 256 Bit Score: 51.01 E-value: 3.89e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  41 VAIieHDGR--VLALRQAHRSG-WSLPGGLIDAGEQPQDAVVREVREETGLDIE------------PGSVM---ATDFDP 102
Cdd:PRK00241 137 VAV--RRGDeiLLARHPRHRNGvYTVLAGFVEVGETLEQCVAREVMEESGIKVKnlryvgsqpwpfPHSLMlgfHADYDS 214

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 308435615 103 -EIRHVDvifrvvcderpevevaSEALESGWFALDELP 139
Cdd:PRK00241 215 gEIVFDP----------------KEIADAQWFRYDELP 236

8-oxo-dGTP diphosphatase MutT;

Pssm-ID: 182721 [Multi-domain] Cd Length: 129 Bit Score: 49.21 E-value: 4.30e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  56 AHRSG-WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMAT-DFDPEIRHVDVIFRVVcdERPEVE-VASEALESGW 132
Cdd:PRK10776  27 AHMAGkWEFPGGKIEAGETPEQALIRELQEEVGITVQHATLFEKlEYEFPDRHITLWFWLV--ESWEGEpWGKEGQPGRW 104


                 ....*.
gi 308435615 133 FALDEL 138
Cdd:PRK10776 105 VSQVAL 110

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

Pssm-ID: 467565 [Multi-domain] Cd Length: 123 Bit Score: 48.83 E-value: 5.65e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 308435615  39 GAVAIIEHDGRVLALRQAHRSG------WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSV 95
Cdd:cd04682    2 GAKLALFLGDKLLTILRDDKPGipfpnlWDLPGGGREGDETPFACVLRELREELGLALPEDRL 64

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: 49.14 E-value: 5.92e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  24 LSHRIVHAMQPTFSAGAVAIIEHDGRVLALRQAHRSG-------WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVM 96
Cdd:cd04700    1 MQHGERTHVPVTLRAAGVVLLNERGDILLVQEKGISGhpekaglWHIPSGAVEDGENPQDAAVREACEETGLRVRLVKFL 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 308435615  97 AT------DFDPEIRHV--------DVIFRVVCDERPEVEVASEALESGWFALDEL 138
Cdd:cd04700   81 GAylgrfpDGVLVLRHVwlaepepgQVLAPAFTDEIAEASFVSREEFAQLYAAGQI 136

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: 49.30 E-value: 8.09e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 308435615  39 GAVAIIE--HDGRVLALRQ----AHRSGWSLPGGLIDAGEQPQDAVVREVREETG 87
Cdd:cd24159   42 GAVAVVPllDDGRVVMERQyrypLKRVFLEFPAGKIDPGEDTLETAKRELLEETG 96

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

Pssm-ID: 467606 [Multi-domain] Cd Length: 174 Bit Score: 49.14 E-value: 1.01e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  36 FSAGAVAIIEHDGRVLALRQ----AHRSGWSLPGGLID-AGEQPQDAVVREVREETGLDIEPGSVMAT-----DFDPEIR 105
Cdd:cd24158   37 PGAVAVVALDDDGRVLLIRQyrhpVRRRLWELPAGLLDvAGEPPLEAAARELAEEADLEAARWEVLVDlftspGFSSEAV 116

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 308435615 106 HVDV---IFRVVCDERPEVEvASEA-LESGWFALDE 137
Cdd:cd24158  117 RVYLargLSEVPEADRHERE-DEEAdMTLRWVPLDE 151

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: 48.89 E-value: 1.13e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 308435615  46 HDGRVlalrqahrsgwSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDF 100
Cdd:cd18869   34 FDGLL-----------GFPGGFVDTGESLEEGLNRELREELGLAHAVFPVTEDDY 77

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: 48.68 E-value: 1.55e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 308435615  40 AVAIIEHD---GRVLALRQ-------AHRSGWSL--PGGLIDAGEQPQDAVVREVREETGLDIE 91
Cdd:cd24155   45 AVAVLPYDpvrDEVVLIEQfrigalaRDESPWLLeiVAGMIDAGETPEDVARREAEEEAGLTLD 108

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: 48.27 E-value: 1.88e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  23 GLSHRIVHamqptfsagaVAIIEHDGRVL-ALRQAHRSGWslPG-------GLIDAGEQPQDAVVREVREETGLDIEPGS 94
Cdd:COG1443   26 GLLHRAFS----------VFVFNSDGRLLlQRRALTKDHW--PGlwdntvcGHPRAGETYEEAAVRELEEELGITVDDDL 93

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 308435615  95 VMATDFDPEIRH--------VDVIFRVVCDERPEV---EVAsealESGWFALDEL 138
Cdd:COG1443   94 RPLGTFRYRAVDanglveneFCHVFVARLDGPLTPqpeEVA----EVRWVTLEEL 144

dihydroneopterin triphosphate pyrophosphatase; Provisional

Pssm-ID: 236516 [Multi-domain] Cd Length: 148 Bit Score: 47.58 E-value: 2.76e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 308435615  41 VAIIEHDGRVLALRQAHRSG-W-SLPGGLiDAGEQPQDAVVREVREETGLDIEPGSVMATD 99
Cdd:PRK09438  12 VVIYTPDLGVLMLQRADDPDfWqSVTGSL-EEGETPAQTAIREVKEETGIDVLAEQLTLID 71

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: 46.83 E-value: 3.66e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  43 IIEHDGRVLaLRQAHRSG-----WSLPGGLIDAGEQPQDAVVREVREETGLDIEPG-----SVMATDFDPEIRHVDVIFR 112
Cdd:cd04683    6 LLVRGDEVL-LLRRANTGyddgwWHLPAGHVEAGETVRAAAVREAKEELGVEIDPEdlrlvHTMHRRSDGGRERIDFFFR 84

                         90       100       110
                 ....*....|....*....|....*....|...
gi 308435615 113 VvcdER----PEVEVASEALESGWFALDELPHP 141
Cdd:cd04683   85 A---TRwsgePRNREPDKCAELRWFPLDALPEN 114

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: 46.69 E-value: 3.83e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  40 AVAIIEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETGLD--IEP--GSVMATDFDPEIRHVDV--IFRV 113
Cdd:cd18883    3 ARGVIISDEHLLLARVKGDDKTFLPGGHIEIGESAEIALVRELREELGLSckVGRylGAVENQWQDKEVIHVELnhLFEV 82

                         90       100       110
                 ....*....|....*....|....*....|
gi 308435615 114 VC--DERPEVEVASEA-LESGWFALDELPH 140
Cdd:cd18883   83 ELqdLHTSDTPESQEPhLEFYWIPYNDLEL 112

mutator mutT protein; All proteins in this family for which functions are known are involved in repairing oxidative damage to dGTP (they are 8-oxo-dGTPases). This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). Lowering the threshold picks up members of MutT superfamily well. [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 200031 [Multi-domain] Cd Length: 128 Bit Score: 46.41 E-value: 4.42e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615   40 AVAIIEHDGRVLALRQAHRSG-----WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDFDPEIRHVDVIFRVV 114
Cdd:TIGR00586   7 AVGIIRNENGEIIITRRADGHmfaklLEFPGGKEEGGETPEQAVVRELEEEIGIPQHFSEFEKLEYEFYPRHITLWFWLL 86

                          90       100
                  ....*....|....*....|.
gi 308435615  115 CDERPEvEVASEALESGWFAL 135
Cdd:TIGR00586  87 ERWEGG-PPGKEGQPEEWWVL 106

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: 45.96 E-value: 9.74e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 308435615  38 AGAVAII-EHDGRVLALRQAHRS----GWSLPGGLIDAGEQPQDAVVREVREETGLD 89
Cdd:cd24160   21 ADAVAVLaLREGRMLFVRQMRPAvgaaTLEIPAGLIDPGETPEEAARRELAEETGLS 77

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: 45.94 E-value: 1.06e-06

                         10        20
                 ....*....|....*....|....*
gi 308435615  63 LPGGLIDAGEQPQDAVVREVREETG 87
Cdd:cd18888   37 FPAGLVDPGESPEQAALRELKEETG 61

nucleoside triphosphatase NudI; Provisional

Pssm-ID: 185369 [Multi-domain] Cd Length: 141 Bit Score: 45.12 E-value: 1.92e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  43 IIEHDGRVLALRQAHRSG-----WSLPGGLIDAGEQPQDAVVREVREETG-----LDIEPGSV-----MATDFD---PEI 104
Cdd:PRK15472  10 LIQNDGAYLLCKMADDRGvfpgqWALSGGGVEPGERIEEALRREIREELGeqlllTEITPWTFrddirTKTYADgrkEEI 89

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 308435615 105 RHVDVIFRVVCDERpEVEVASEALESGWFALDELPHPD 142
Cdd:PRK15472  90 YMIYLIFDCVSANR-DVKINEEFQDYAWVKPEDLVHYD 126

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

Pssm-ID: 131752 Cd Length: 156 Bit Score: 45.44 E-value: 1.94e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 308435615   37 SAGAVAIIEHDGRVLALRQAHRSGWSLPGGLIDAGEQPQDAVVREVREETG 87
Cdd:TIGR02705  23 NPNHVLVIPRYKDQWLLTEHKRRGLEFPGGKVEPGETSKEAAIREVMEETG 73

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

Pssm-ID: 442065 [Multi-domain] Cd Length: 288 Bit Score: 46.06 E-value: 2.29e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  44 IEHDGRVLALRQAHRSG--WSLPGGLIDAGEQPQDAVVREVREETGLDIE------------PGSVM----ATDFDPEIr 105
Cdd:COG2816  165 VTDGDRILLARQARWPPgrYSLLAGFVEPGETLEQAVRREVFEEVGVRVKnvryvgsqpwpfPSSLMlgftAEADSGEI- 243

                         90       100       110
                 ....*....|....*....|....*....|....
gi 308435615 106 HVDvifrvvcderpEVEVAsealESGWFALDELP 139
Cdd:COG2816  244 TVD-----------GDEIE----DARWFSRDELP 262

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: 44.27 E-value: 2.38e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 308435615  40 AVAIIEHDGRVLALRQaHRSG---WSLPGGLIDAGEQPQDAVVREVREETGLDIE 91
Cdd:cd04669    3 AVLVIYDDDKLLLIRR-TKPGeeyYVFPGGGIEPGETPEEAALREAVEELGLDVA 56

nudix hydrolase

Pssm-ID: 215184 [Multi-domain] Cd Length: 144 Bit Score: 44.47 E-value: 2.92e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  33 QPTFSAGAVAIIEHDGRVLALRQAHRSGWS---LPGGLIDAGEQPQDAVVREVREETGLDIEP---GSVMATDFDPEIR- 105
Cdd:PLN02325   5 EPIPRVAVVVFLLKGNSVLLGRRRSSIGDStfaLPGGHLEFGESFEECAAREVKEETGLEIEKielLTVTNNVFLEEPKp 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 308435615 106 --HVDVIFRVVCDERPEVEVASEALES---GWFALDELPHP 141
Cdd:PLN02325  85 shYVTVFMRAVLADPSQVPQNLEPEKCygwDWYEWDNLPEP 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: 467547 Cd Length: 147 Bit Score: 43.72 E-value: 6.47e-06

                         10        20        30
                 ....*....|....*....|....*....|....
gi 308435615  57 HRSGWSLPGGLIDAGEQPQDAVVREVREETGLDI 90
Cdd:cd04662   31 DEGAWSIPKGEVEPGEDPLAAARREFEEETGFPA 64

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: 43.40 E-value: 6.77e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  42 AIIEHDGRVLALRQAHRSG-----WSLPGGLIDAGEQPQDAVVREVREETGLD------IEPGSVMATDfDPEIRHVDVI 110
Cdd:cd18872    5 SFLFHDGKVLLFRRSDKVGtyqgrWAGISGSIESDDPPLAAAWREIREETGLTpedvelLRQGKPFEFT-DESLGREWTV 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 308435615 111 --FRVVCDERPEVEVASEALESGWFALDEL------PHPDKSTRRI 148
Cdd:cd18872   84 hpFLFRLKDDRAIKLDWEHTEWEWVDPTDIldyetvPRLWESLRRV 129

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 44.09 E-value: 1.31e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 308435615  27 RIVHAMqptfsagAVAIIEHDGRVL-ALRQAHR--SG-WSLPGGLIDAGEQPQDAVVREVREETGLDI 90
Cdd:PRK08999   3 KRIHVA-------AGVIRDADGRILlARRPEGKhqGGlWEFPGGKVEPGETVEQALARELQEELGIEV 63

NUDIX domain family NudE found in Escherichia coli, and similar proteins; The adenosine nucleotide hydrolase NudE protein in Escherichia coli is a NUDIX hydrolase family member active against ADP ribose, NADH, AP2A and AP3A33, and is classified as a hydrolase (E.C. 3.6.1.-) based on gene annotations. It is an ADPRase (EC 3.6.1.13) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the NUDIX hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also contains a 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467604 [Multi-domain] Cd Length: 134 Bit Score: 42.23 E-value: 1.51e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 308435615  39 GAVAI--IEHDGRVLALRQ----AHRSGWSLPGGLIDAGEQPQDAVVREVREETGL 88
Cdd:cd24156    3 GAVMIvpILDDDHLLLIREyaagTERYELGFPKGLIDPGETPEEAANRELKEEIGF 58

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: 42.55 E-value: 1.54e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 308435615  23 GLSHRIVHamqptfsagaVAIIEHDGRVLALRQahRSGW--SLPG-------GLIDAGEQPQDAVVREVREETGLDIEP 92
Cdd:cd04692   23 GLWHRTVH----------VWLVNPEEGRLLLQK--RSANkdDFPGlwdisaaGHIDAGETYEEAAVRELEEELGLTVSP 89

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: 42.16 E-value: 1.69e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 308435615  37 SAGAVAIIEhDGRVLALRQ----AHRSGWSLPGGLIDAGEQPQDAVVREVREETGL 88
Cdd:cd24161    5 AVGVLPITD-DGEVVLVEQyrypLGGWSWEIPAGGWPEGEDPEEAARRELREETGL 59

NUDIX domain;

Pssm-ID: 464330 [Multi-domain] Cd Length: 114 Bit Score: 40.37 E-value: 5.48e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615   40 AVAIIEHDGRVLaLRQAHRSG-----WSLPGGLIDAGEQPQDAVVRevREETGLDIEPGSVMatdfdpEIRHV--DVIFR 112
Cdd:pfam14815   2 VLVIRNGDGRVL-LRKRPEKGllgglWEFPGGKVEPGETLEEALAR--LEELGIEVEVLEPG------TVKHVftHFRLT 72

                          90       100
                  ....*....|....*....|....*..
gi 308435615  113 VVCDERPEVEVASEALESG-WFALDEL 138
Cdd:pfam14815  73 LHVYLVREVEGEEEPQQELrWVTPEEL 99

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: 39.92 E-value: 1.29e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 308435615  43 IIEHDGRVLALRQAHRSG-----WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGSVMATDFDPEIR 105
Cdd:cd04696    8 LIENEGCYLLCKMADDRGvfpgqWALSGGGVEPGERIEEALRREIREELGEQLILSDITPWTFRDDIR 75

adenosine nucleotide hydrolase NudE; Provisional

Pssm-ID: 183303 Cd Length: 185 Bit Score: 40.17 E-value: 1.54e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  15 RVY-RMLPAGlshrivhamqptfsAGAVAI--IEHDGRVLALRQ----AHRSGWSLPGGLIDAGEQPQDAVVREVREETG 87
Cdd:PRK11762  37 RVYeRMRPSG--------------RGAVMIvpILDDDTLLLIREyaagTERYELGFPKGLIDPGETPLEAANRELKEEVG 102


                 .
gi 308435615  88 L 88
Cdd:PRK11762 103 F 103

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: 1.93e-04

                         10        20        30
                 ....*....|....*....|....*....|...
gi 308435615  61 WSLPGGLIDAGEQPQDAVVREVREETGLDIEPG 93
Cdd:COG4119   38 WSIPKGEYEPGEDPLAAARREFAEETGVPAPDG 70

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

Pssm-ID: 467532 [Multi-domain] Cd Length: 158 Bit Score: 39.40 E-value: 2.15e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  40 AVAIIEHDGR---VLALRQAHR---SG-WSLPGGLIDAG-EQPQDAVVREVREETGLDIE 91
Cdd:cd03426    6 LIPLVEGDGElhvLLTKRASHLrshPGqIAFPGGKREPGdESPVETALRETEEEIGLPPE 65

GDP-mannose hydrolase (GDPMK), and similar proteins; GDP-mannose hydrolase (GDPMK) is a NUDIX enzyme that uses GDP-mannose as the preferred substrate. It is distinct from Nudix ADP-ribose hydrolases. GDPMK and ADP-ribose pyrophosphatase seem to use similar catalytic mechanism. However, GDPMK hydrolysis does not rely on a single glutamate as the catalytic base; rather, it is dependent on residues that coordinate the magnesium ions and residues that position the substrate properly for catalysis. 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: 467605 Cd Length: 146 Bit Score: 38.70 E-value: 3.29e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 308435615  40 AVAIIEHD---GRVLALRQ-------AHRSGWSL--PGGLIDaGEQPQDAVVREVREETGLDIE 91
Cdd:cd24157    6 AAAVLLYDpkrKTVVLVRQfrapaylGGGDGWLIeaCAGLLD-GDDPEDCIRREAEEETGYRLG 68

Uncharacterized conserved protein [Function unknown];

Pssm-ID: 443287 [Multi-domain] Cd Length: 170 Bit Score: 37.84 E-value: 8.65e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  62 SLPGGLIDAGEQPQDAVVREVREETGLdiEPGSV--MAT----DFDPEIRHVDVI-FRVVcdeRPEVEVASEALESGWFA 134
Cdd:COG4111    1 ALPGGFVREHESLEDAARRWLAEQTGL--ELGYLeqLYTfgdpDRDPRGRVISVAyLALV---REEELRADDADDAAWFP 75


                 ....*.
gi 308435615 135 LDELPH 140
Cdd:COG4111   76 VDELPP 81

thiamine diphosphokinase Tnr3 from Schizosaccharomyces pombe and similar proteins; Tnr3 is a bifunctional enzyme composed of a C-terminal thiamine pyrophosphokinase domain, which transfers pyrophosphate from ATP to thiamine and an N-terminal NUDIX hydrolase domain that converts oxidized derivatives of thiamine diphosphate (oxothiamine and oxythiamine) to their respective monophosphates. 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, 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: 467544 Cd Length: 153 Bit Score: 35.55 E-value: 5.06e-03

                         10        20
                 ....*....|....*....|....*..
gi 308435615  65 GGLIDAGEQPQDAVVREVREETGLDIE 91
Cdd:cd03676   44 AGGVPAGESPLETLVREAEEEAGLPED 70

diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 and similar proteins; Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 (DIPP2), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 4; Nudt4, and other proteins including DIPP1/Nudt3, DIPP3a;APS2/Nudt10 and DIPP3beta;APS1/Nudt11. DIPP regulates the turnover of diphosphoinositol polyphosphates. The turnover of these high-energy diphosphoinositol polyphosphates represents a molecular switching activity with important regulatory consequences. Molecular switching by diphosphoinositol polyphosphates may contribute to regulating intracellular trafficking. Several alternatively spliced transcript variants have been described, but the full-length nature of some variants has not been determined. Isoforms DIPP2alpha and DIPP2beta are distinguishable from each other solely by DIPP2beta possessing one additional amino acid due to intron boundary skidding in alternate splicing. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467551 [Multi-domain] Cd Length: 128 Bit Score: 35.20 E-value: 5.55e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 308435615  38 AGAVAIIEHDGRVLAL----RQAHRsgWSLPGGLIDAGEQPQDAVVREVREETGL 88
Cdd:cd04666    3 AGALPYRITKGELEVLlitsRKTGR--WILPKGGPEKGETPAEAAAREAWEEAGV 55

C-terminal domain of DNA glycosylase; DNA glycosylase (MutY in bacteria and hMYH in humans) is responsible for repairing misread A*oxoG residues to C*G by removing the inappropriately paired adenine base from the DNA backbone. It belongs to the NUDIX hydrolase superfamily and is important for the repair of various genotoxic lesions. Enzymes belonging to this superfamily requires a divalent cation, such as Mg2+ or Mn2+ for their activity. They are also recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V). However, DNA glycosylase does not seem to contain this signature motif. DNA glycosylase consists of 2 domains: the N-terminal domain contains the catalytic properties of the enzyme and the C-terminal domain affects substrate (oxoG) binding and enzymatic turnover. The C-terminal domain is highly similar to MutT, based on secondary structure and topology, despite low sequence identity. MutT sanitizes the nucleotide precursor pool by hydrolyzing oxo-dGTP to oxo-dGMO and inorganic pyrophosphate. The similarity strongly suggests that the two proteins share a common evolutionary origin.

Pssm-ID: 467537 [Multi-domain] Cd Length: 118 Bit Score: 34.97 E-value: 5.98e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308435615  39 GAVAIIEHDGRVLaLRQAHRSG-----WSLPGGLIDAGEQPQDAVVREVREETGLDIEPGsvmatdfdPEIRHV------ 107
Cdd:cd03431    6 FTVLVLRDGGRVL-LEKRPEKGllaglWEFPLVETEEEEEEAEALLGLLAEELLLILEPL--------GEVKHVfshfrl 76

                         90       100       110
                 ....*....|....*....|....*....|..
gi 308435615 108 DV-IFRVVCDERPEVevasEALESGWFALDEL 138
Cdd:cd03431   77 HItVYLVELPEAPPA----APDEGRWVDLEEL 104