NCBI Conserved Domain Search

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

Pssm-ID: 467543 [Multi-domain] Cd Length: 138 Bit Score: 244.36 E-value: 1.35e-84

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   7 VTVATIVEDQGRFLLVEEQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPSNGVTYQRVCF 86
Cdd:cd03675   1 VTVAAVVERDGRFLLVEEETDGRLVLNQPAGHLEPGESLLEAAIRETLEETGWEVEPTALLGIYQWTAPDNGVTYLRFAF 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15597821  87 AARPVRHHPERALDDGIIGPRWLTRDELAAQPQRWRSHLVLRCIDDYLAGGRYPLALI 144
Cdd:cd03675  81 AGELLEHLPDQPLDSGIIRAHWLTLEEILALQARLRSPLVLRCIEDYLAGQRYPLSLI 138

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 83.10 E-value: 2.71e-21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   1 MSWHPHVTVATIVED-QGRFLLVEEQAD-GREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTapsNG 78
Cdd:COG1051   1 MTKVPKVAVDAVIFRkDGRVLLVRRADEpGKGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHP---DR 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 15597821  79 VTYQRVCFAARPVRHHPEraLDDGIIGPRWLTRDELAAQPQRWRSHLVLR 128
Cdd:COG1051  78 GHVVSVAFLAEVLSGEPR--ADDEIDEARWFPLDELPELAFTPADHEILE 125

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: 78.22 E-value: 1.50e-19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   6 HVTVATIVEDQGRFLLVEEQA-DGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPSNGVTYQRV 84
Cdd:cd02883   1 VAVGAVVFDDEGRVLLVRRSDgPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEGRHVVVL 80

                        90       100
                ....*....|....*....|....*.
gi 15597821  85 CFAARPVRHHPERALDDGIIGPRWLT 110
Cdd:cd02883  81 VFLARVVGGEPPPLDDEEISEVRWVP 106

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: 72.37 E-value: 6.91e-17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   5 PHVTVATIVEDQGRFLLVEE--QADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVElsavTGIYLYTAPSNGVTYQ 82
Cdd:COG0494  13 RPAVVVVLLDDDGRVLLVRRyrYGVGPGLWEFPGGKIEPGESPEEAALRELREETGLTAE----DLELLGELPSPGYTDE 88

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15597821  83 RV-CFAARPVRHHPERALD--DGIIGPRWLTRDELAAQPQRWRSHLVLRCIDDYL 134
Cdd:COG0494  89 KVhVFLARGLGPGEEVGLDdeDEFIEVRWVPLDEALALVTAGEIAKTLAALARLL 143

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 67.51 E-value: 3.57e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821     4 HPHVTVATIVED-QGRFLLVEE-QADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPSNGVTY 81
Cdd:pfam00293   1 KRRVAVGVVLLNeKGRVLLVRRsKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRFP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 15597821    82 Q---RVCFAARPVRHHPERALDDGIIGPRWLTRDELAAQPQRWRSHLVLR 128
Cdd:pfam00293  81 DeheILYVFLAEVEGELEPDPDGEVEEVRWVPLEELLLLKLAPGDRKLLP 130

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: 67.15 E-value: 5.18e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   4 HPH-VTVATIVEDqGRFLLVEE--QADGREVLNQPAGHLEPAESLLEAALRETLEETGWEV-ELSAVTGIYLYTAPSNGV 79
Cdd:cd03424   1 HPGaVAVLAITDD-GKVVLVRQyrHPVGRVLLELPAGKIDPGEDPEEAARRELEEETGYTAgDLELLGSFYPSPGFSDER 79

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 15597821  80 TYqrvCFAARPVRHHPERALDDG-IIGPRWLTRDELAA 116
Cdd:cd03424  80 IH---LFLAEDLTPVSEQALDEDeFIEVVLVPLEEALE 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: 467559 [Multi-domain] Cd Length: 144 Bit Score: 62.81 E-value: 3.85e-13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   4 HPHVTvATIVEDQGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVELSAVTGI-----YLYTAPsNG 78
Cdd:cd04676  17 TPSVA-AVILNEDGRILLQRKGGLGLWSL--PAGAIEPGEHPAEAVIREVREETGLLVKPTRLLGVfggkeFRYTYP-NG 92

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 15597821  79 --VTYQRVCFAARpVRHHPERALDDGIIGPRWLTRDE 113
Cdd:cd04676  93 dqVEYTVIAFKCV-VTGGTLNAIDGETSELRYFSRTQ 128

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: 58.33 E-value: 1.10e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  14 EDQGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPSNG------VTYqrvcFA 87
Cdd:cd03673  13 GGGGEVLLIHRPRYDDWSL--PKGKLEPGETPEEAAVREVEEETGLRVRLGRPLGTTRYTYTRKGkgilkkVHY----WL 86

                        90       100
                ....*....|....*....|....*..
gi 15597821  88 ARPVRHHPERALDDGIIGPRWLTRDEL 114
Cdd:cd03673  87 MRALGGEFLPQPEEEIDEVRWLPPDEA 113

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

Pssm-ID: 467542 [Multi-domain] Cd Length: 130 Bit Score: 57.65 E-value: 2.24e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   6 HVTVATIV--EDQGRFLLVEEQADGRevLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLY------TAPSN 77
Cdd:cd03674   1 HFTASAFVvnPDRGKVLLVHHRKLGR--WLQPGGHVEPDEDPLEAALREAREETGLDVELLSPLSPDPLdidvhpIPANP 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 15597821  78 GVTYQR---VCFAARPVRHHPERALDDgIIGPRWLTRDELAAQ 117
Cdd:cd03674  79 GEPAHLhldVRYLAVADGDEALRKSDE-SSDVRWFPLDELEEL 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: 467579 [Multi-domain] Cd Length: 118 Bit Score: 55.71 E-value: 1.06e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   6 HVTVATIVEDQGRFLLVEEQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLY-TAPSNGVTYqrV 84
Cdd:cd04699   2 PVSVKGVIFDNGRVLLLRRSRAGAGEWELPGGRLEPGESPEEALKREVKEETGLDVSVGELLDTWTFeLDPDKGVFI--V 79

                        90       100       110
                ....*....|....*....|....*....|...
gi 15597821  85 CFAARPVRHHPEraLDDGIIGPRWLTRDELAAQ 117
Cdd:cd04699  80 TYLCRLVGGEVT--LSDEHEEYEWVTPEELAEL 110

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: 55.39 E-value: 1.47e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   6 HVTVATIVEDQGRFLLVEE-QADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAvtgiyLYTAPSNGVTYQRV 84
Cdd:cd04671   1 YVVAAVIINEQGEVLMIQEaKRSCRGKWYLPAGRVEPGESIVEAAKREVKEETGLKCEPST-----LLSVEEAGGSWYRF 75

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 15597821  85 CFAARPV---RHHPERALDDGIigpRWLTRDELaaqpqrwRSHLVLRCID 131
Cdd:cd04671  76 VFTGNITggkLKTPADADSESL---QAFWIDDI-------STKLPLRAHD 115

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

Pssm-ID: 467564 [Multi-domain] Cd Length: 135 Bit Score: 54.11 E-value: 4.73e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   9 VATIVEDQGRFLLVE---EQADGRevLNQPAGHLEPAESLLEAALRETLEETGWEVE----LSAVTGIYLYtapsNGVTY 81
Cdd:cd04681   9 VGVIIRNEGEILFVRrakEPGKGK--LDLPGGFVDPGESAEEALRRELREELGLKIPklryLCSLPNTYLY----KGITY 82

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 15597821  82 qRVC---FAARpVRHHPE--RALDDgIIGPRWLTRDEL 114
Cdd:cd04681  83 -KTCdlfFTAE-LDEKPKlkKAEDE-VAELEWLDLEEI 117

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: 54.06 E-value: 5.45e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   7 VTVATIVEDQGRFLLVE---EQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIY--LYTAPSNGVTY 81
Cdd:cd04673   2 VAVGAVVFRDGRVLLVRrgnPPDAGLWSF--PGGKVELGETLEDAALRELREETGLEAEVVGLLTVVdvIERDEAGRVRF 79

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 15597821  82 QRVC--FAARPVRHHPeRALDDGiIGPRWLTRDELAAQP 118
Cdd:cd04673  80 HYVIldFLAEWVSGEP-VAGDDA-LDARWFSLEELDGLP 116

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

Pssm-ID: 467590 [Multi-domain] Cd Length: 142 Bit Score: 54.13 E-value: 6.94e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   3 WHPHVTvATIVEDQGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVE---LSAVTGIYLYTAPsNG- 78
Cdd:cd18879  17 WLPGVT-AVVLRDAGRVLLVRRADNGRWTP--VTGIVEPGEQPADAAVREVLEETGVDVEverLASVGASPPVTYP-NGd 92

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 15597821  79 -VTYQRVCFAARPVRHHPeRALDDGIIGPRWLTRDELAAQPQRWR 122
Cdd:cd18879  93 qCQYLDLTFRCRPVGGEA-RVNDDESLEVGWFPVDALPPMLPRFR 136

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: 51.02 E-value: 7.81e-09

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15597821   9 VATIVEDQGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVEL 63
Cdd:cd03428   9 IYRRDNGEIEFLLLQHSYGGHWDF--PKGHVEPGESELETALRETKEETGLTVDD 61

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

Pssm-ID: 467572 [Multi-domain] Cd Length: 123 Bit Score: 50.61 E-value: 9.21e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   7 VTVATIVEDQGRFLLVEEQadGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPS---NGVTYQR 83
Cdd:cd04690   2 VKAAVIIIKDGRLLLVRKR--GTDAFYLPGGKREPGETPLQALVRELKEELGLDLDPDSLRFLGTFEAPAanePGTTVRM 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 15597821  84 VCFAARPvrhhperaldDGIIGP-------RWLTRDELAA 116
Cdd:cd04690  80 TCFTADY----------DGEPQPaaeieelRWLDPADPDD 109

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: 50.61 E-value: 1.01e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   6 HVTVATIV-EDQGRFLLVEEQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIylytapsngvtyqrv 84
Cdd:cd04670   2 QVGVGGLViNENNEVLVVQEKYGGPGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGF--------------- 66

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15597821  85 cfaarpvRHHPE--------------RALDDGIIGP--------RWLTRDELAAQPQ 119
Cdd:cd04670  67 -------RHQHPgrfgksdlyfvcrlRPLSDEEIKIcpeeiaeaKWMPLEEYLKQPN 116

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: 50.25 E-value: 1.16e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   5 PHVTVATIV-EDQGRFLLVE-EQADGREVLNQPAGHLEPAESLLEAALRETLEETG---WEVELSAVTGIYLYTAPSNGV 79
Cdd:cd04678   1 PRVGVGVIVlNDDGKVLLGRrKGSHGAGTWALPGGHLEFGESFEECAAREVLEETGleiRNVRFLTVTNDVFEEEGKHYV 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 15597821  80 TyqrVCFAARPVRHHPERAL-DDGIIGPRWLTRDELAAQPQ 119
Cdd:cd04678  81 T---IFVLAEVDDGEPEENMePDKCEGWEWFSWDELPPLRP 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: 467573 [Multi-domain] Cd Length: 122 Bit Score: 49.99 E-value: 1.46e-08

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15597821   7 VTVATIVEDQGRFLLVEEQ---ADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVELSAVTGI 69
Cdd:cd04691   2 LGVGGVVVKEGKVLLVKRAygpGKGRWTL--PGGFVEEGETLDEAIVREVLEETGIDAKPVGIIGV 65

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: 50.20 E-value: 2.24e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   9 VATIVEDQGRFLLVEEQ--ADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPSNGVTYQRVCF 86
Cdd:cd24160  24 VAVLALREGRMLFVRQMrpAVGAATLEIPAGLIDPGETPEEAARRELAEETGLSGDLTYLTRFYVSPGFCDEKLHVFLAE 103

                        90       100
                ....*....|....*....|..
gi 15597821  87 AARPVRHHPEralDDGIIGPRW 108
Cdd:cd24160 104 NLREVEAHPD---EDEAIEVVW 122

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: 48.79 E-value: 3.60e-08

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 15597821   9 VATIVEDQGRFLLVEEQAdgREVLNQPAGHLEPAESLLEAALRETLEETG 58
Cdd:cd04665   3 VVVIARYKGKWLFTRHKE--RRGWEFPGGKREPGETIEEAARRELYEETG 50

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: 49.05 E-value: 4.30e-08

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15597821  12 IVEDQGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVE----LSAVTGIYLYTAPSNG 78
Cdd:cd04677  19 ILNEQGRILLQKRTDTGDWGL--PGGAMELGESLEETARREVFEETGLTVEelelLGVYSGKDLYYTYPNG 87

NUDIX family Ndx2; NUDIX family protein Ndx2 found in Thermus thermophilus has ADP-ribose pyrophosphatase (ADPRase) as well as flavin adenine dinucleotide (FAD) activity. ADPRase (EC 3.6.1.13) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the NUDIX hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also contains a 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity.Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467609 [Multi-domain] Cd Length: 137 Bit Score: 49.09 E-value: 4.44e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  13 VEDQGRFLLVEEQadgREVLNQ-----PAGHLEPAESLLEAALRETLEETGWEVE-LSAVTGIYlytaPSNGVTYQR-VC 85
Cdd:cd24161  11 ITDDGEVVLVEQY---RYPLGGwsweiPAGGWPEGEDPEEAARRELREETGLRAErWTPLGRFY----PSNGVSDERaHV 83

                        90       100       110
                ....*....|....*....|....*....|.
gi 15597821  86 FAARPVRHHpERALDD--GIIGPRWLTRDEL 114
Cdd:cd24161  84 FLATGLTPG-EPAPEEteEDLEVRRVPLAEA 113

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: 48.29 E-value: 7.53e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  10 ATIVEDqGRFLLVEEQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYtAPSNGVTYQ-RVCFAA 88
Cdd:cd18880   6 AIIIED-GKLLLVKHRDEGGIFYILPGGGQEHGETLPEALKRECLEETGLDVEVGDLLFVREY-IGPNKPVHQvELFFLC 83

                        90       100       110
                ....*....|....*....|....*....|..
gi 15597821  89 RPVRHHPERALDDG--IIGPRWLTRDELAAQP 118
Cdd:cd18880  84 TLEGGELTLGSDPDlnQVGVEWIPLEELDSIR 115

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

Pssm-ID: 467587 [Multi-domain] Cd Length: 144 Bit Score: 48.33 E-value: 1.05e-07

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15597821  12 IVEDQGRFLLVEEQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPSNG 78
Cdd:cd18875   9 IYDGEDRVLVLDRVKKDWGGYTFPGGHVEPGESFVDSVIREVKEETGLTIKNPELCGIKQWINPDGE 75

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: 47.67 E-value: 1.42e-07

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   7 VTVATIVED-QGRFLLVEEQADGREVLNQ---PAGHLEPAESLLEAALRETLEETGWEVE 62
Cdd:cd04694   3 VGVVVLIEDsDDRVLLTRRAKHMRTFPGVwvpPGGHVELGESLLEAGLRELQEETGLEVS 62

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

Pssm-ID: 467545 [Multi-domain] Cd Length: 123 Bit Score: 46.80 E-value: 2.09e-07

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15597821   5 PHVTVATIVEDQGRFLLVEEQADGREVL-NQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIY 70
Cdd:cd04511   1 PKIVVGCLPEWEGKVLLCRRAIEPRKGYwTLPAGFMELGETTEQGAARETREEAGARVEIGSLYAVY 67

MutT homolog-1 and similar proteins; MutT homolog-1 (MTH1), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 1/Nudt1, is a member of the NUDIX hydrolase superfamily. MTH1, the mammalian counterpart of MutT, hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-ATP, to monophosphates, thereby preventing the incorporation of such oxygen radicals during replication. This is an important step in the repair mechanism in genomic and mitochondrial DNA. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity, and contain the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. MTH1 is predominantly localized in the cytoplasm and mitochondria. Structurally, this enzyme adopts a similar fold to MutT despite low sequence similarity outside the conserved NUDIX motif. The most distinctive structural difference between MutT and MTH1 is the presence of a beta-hairpin, which is absent in MutT. This results in a much deeper and narrower substrate binding pocket. Mechanistically, MTH1 contains dual specificity for nucleotides that contain 2-OH-adenine bases and those that contain 8-oxo-guanine bases.

Pssm-ID: 467596 [Multi-domain] Cd Length: 147 Bit Score: 47.23 E-value: 2.72e-07

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15597821   8 TVATIVEDqGRFLLVEEQADGREVL-NQPAGHLEPAESLLEAALRETLEETGWEVE 62
Cdd:cd18886   3 TLCFIIRD-DEVLLLNRNKKPNMGKwNGVGGKLEPGESPEECAIREVFEETGLELE 57

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: 46.40 E-value: 4.24e-07

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15597821   5 PHVTV-ATIVEDqGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIY 70
Cdd:cd04672   1 PKVDVrAAVFKD-GKILLVREKSDGRWTL--PGGWADVGLSPAENAVKEVREESGYEVRARKLLAVF 64

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 46.93 E-value: 9.01e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821    7 VTVATIVEDQGRFLLVEEQAD-GREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTG------IYLYTAPS-NG 78
Cdd:PRK05379 204 VTVDAVVVQSGHVLLVRRRAEpGKGLWALPGGFLEQDETLLDACLRELREETGLKLPEPVLRGsirdqqVFDHPGRSlRG 283

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 15597821   79 VTYQRVCFAARPVRHHPERALDDGIIGPRWLTRDELAAQPQRW 121
Cdd:PRK05379 284 RTITHAFLFEFPAGELPRVKGGDDADKARWVPLAELLAMRDRM 326

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: 45.26 E-value: 1.08e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  12 IVEDQGRFLLVE---EQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLY---TAPSNGVTY-QR- 83
Cdd:cd04685   7 LLDPDGRVLLFRfhdPDDPGRSWWFTPGGGVEPGESPEQAAVRELREETGLRLEPDDLGGPVWRrraVFDFSGETVrQDe 86

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 15597821  84 VCFAARPVRHHPERAL-----DDGIIGPRWLTRDELAAQPQR 120
Cdd:cd04685  87 RFFLVRVPAFEVDTAGwtdleRAVIDGHRWWSLAELAATGET 128

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

Pssm-ID: 467593 [Multi-domain] Cd Length: 130 Bit Score: 44.17 E-value: 2.33e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   5 PHVTVATIVEDQGRFLLVeeQADGREVLNQPA------GHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPSNG 78
Cdd:cd18882   1 HEVAIAILYDDRGKVLLQ--LRDDKPGIPYPGywglfgGHLEPGETPEEAIRRELEEEIGYEPGEFRFFLLYTEDDGEDR 78


                ...
gi 15597821  79 VTY 81
Cdd:cd18882  79 IRH 81

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: 44.21 E-value: 2.47e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   9 VATIVEDQGRFLLVEEQADGREVLNQ-PAGHLEPAESLLEAALRETLEETGWEVELSAVT-GIYLYTAPSNgvtYQRVCF 86
Cdd:cd04663   4 CAYVTRGRNRELLVFEHPDFPEAGLQvPKGTVEPGESPEEAALRELAEETGLTGARVVVDlGSHDEGFEEL---HQRWFF 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 15597821  87 AARPVRHHPER----ALDDGIIGP-----RWLtrdELAAQPQRW 121
Cdd:cd04663  81 HLCLAGEPPERwehhETDDGEGGGlrfefFWV---PLAAAPPRL 121

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: 43.95 E-value: 3.11e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15597821   5 PHVTV-ATIVEDQGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVE 62
Cdd:cd18890   1 PKVDIrAVVFNDKEEILLVKEKEDGKWTL--PGGWADVGYTPTEVAAKEVEEETGLEVS 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: 467553 [Multi-domain] Cd Length: 120 Bit Score: 43.50 E-value: 3.44e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  12 IVEDQGRFLLVEEQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVelsAVTGIYLYTAPSNGVT----YQRVCFA 87
Cdd:cd04669   6 VIYDDDKLLLIRRTKPGEEYYVFPGGGIEPGETPEEAALREAVEELGLDV---AVTLITLILRVLNDGTqhyfLARVITG 82

                        90       100       110
                ....*....|....*....|....*....|....
gi 15597821  88 ARPVRHHPER-ALDDGIIGPRWLTRDELAAQPQR 120
Cdd:cd04669  83 SFGLGTGPEFeRPERGTYEPVWVPLTALPALNLR 116

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: 43.76 E-value: 3.63e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  10 ATIVEDQGRFLLVEeQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIY-LYTAPSNGVTYQR-VC-- 85
Cdd:cd04684  20 AVIFNDEGKVLLVQ-TPNGGYFL--PGGGIEPGETPEEALHREVLEETGWEIEIGEFLGNAsRYFYSPDYDRYYLnIGyf 96


                ....*..
gi 15597821  86 FAARPVR 92
Cdd:cd04684  97 YLAELVR 103

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: 43.01 E-value: 7.82e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 15597821  12 IVEDQGRFLLVEeQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVE 62
Cdd:cd04664   9 RKDEEGEVLLLK-RTDDGGFWQSVTGGIEDGETPWQAALRELKEETGLDPL 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: 467566 [Multi-domain] Cd Length: 137 Bit Score: 42.59 E-value: 1.24e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   7 VTVATIVEDQGRFLLVEEQ----ADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVE 62
Cdd:cd04683   1 VDVHLLLVRGDEVLLLRRAntgyDDGWWHL--PAGHVEAGETVRAAAVREAKEELGVEID 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: 467552 [Multi-domain] Cd Length: 117 Bit Score: 41.89 E-value: 1.29e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  10 ATIVEDQGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETGweveLSAVTGIYL--YTAPSN 77
Cdd:cd04667   3 ATVICRRGDRILLVARRGGRWLL--PGGKIEPGESPLEAAIRELKEETG----LAALSLLYLfeHEGPHK 66

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: 42.13 E-value: 1.41e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   6 HVTVATIVEDQGRFLLveeqadGRE-------VLNQPAGHLEPAESLLEAALRETLEETG 58
Cdd:cd03427   2 LTTLVFVLRGDDRVLL------GLKkrgfgagKWNGFGGKVEPGETIEEAAVRELEEEAG 55

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: 42.08 E-value: 2.08e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  35 PAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPsnGVTYQRVCFA------ARPVRHHPERALDDG-IIGPR 107
Cdd:cd18888  38 PAGLVDPGESPEQAALRELKEETGYTGEKVLSVSPPLALDP--GLSNANMKLVtvevdgDDPENQNPKQELEDGeFIEVI 115


                ....*..
gi 15597821 108 WLTRDEL 114
Cdd:cd18888 116 LVPLNEL 122

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: 41.21 E-value: 5.10e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   4 HPHVTVATIVEDQGRFLLVEE--QADGREVLNQPAGHLEPAESLLEAALRETLEETGWEvelsAVTGIYLYTApSNGVTY 81
Cdd:cd24159  40 HPGAVAVVPLLDDGRVVMERQyrYPLKRVFLEFPAGKIDPGEDTLETAKRELLEETGYE----AQEWAFLTTI-HPAIGY 114

                        90       100
                ....*....|....*....|....
gi 15597821  82 QRVC---FAARPVRhHPERALDDG 102
Cdd:cd24159 115 SNEHieiYLARGLT-HVEQKLDDG 137

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: 40.13 E-value: 7.25e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   6 HVTVAtIVEDQGRFLLV-----EEQADGREVlnqPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPSNGVT 80
Cdd:cd03425   2 EVVAA-IIVDDGRVLIAqrpegKHLAGLWEF---PGGKVEPGETPEQALVRELREELGIEVEVGEPLGTVEHDYPDFHVR 77

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 15597821  81 YqrVCFAARPVRHHPeRALDDGIIgpRWLTRDELAA 116
Cdd:cd03425  78 L--HVYLCTLWSGEP-QLLEHQEL--RWVTPEELDD 108

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

Pssm-ID: 467586 [Multi-domain] Cd Length: 125 Bit Score: 39.96 E-value: 7.40e-05

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15597821   5 PHVTV-ATIVEDQGRFLLVEeQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEV 61
Cdd:cd18874   1 PEPTVgALIFNPDGKVLLVR-SHKWNDLYGIPGGKVEWGETLEEALKREVKEETGLDI 57

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: 40.57 E-value: 8.95e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  36 AGHLEPAESLLEAALRETLEETGWEVELS-AVTGIYLYTAP-SNGVTYQRVC--FAAR---PVRHHPERAlDDGiigpRW 108
Cdd:COG1443  64 CGHPRAGETYEEAAVRELEEELGITVDDDlRPLGTFRYRAVdANGLVENEFChvFVARldgPLTPQPEEV-AEV----RW 138

                        90
                ....*....|....*...
gi 15597821 109 LTRDELAAQPQRWRSHLV 126
Cdd:COG1443 139 VTLEELLALLEAGPEAFT 156

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: 39.58 E-value: 1.16e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   6 HVTVATIVEDQGRFLLVEEQA---DGRevLNQPAGHLEPAESLLEAALRETLEETGWEVE 62
Cdd:cd04686   1 HFGVYGIIIRNDKLLLIRKTRgpyQGR--YDLPGGSQEFGESLEDALKREFAEETGMTVT 58

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

Pssm-ID: 467604 [Multi-domain] Cd Length: 134 Bit Score: 39.15 E-value: 1.82e-04

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 15597821  13 VEDQGRFLLVEEQADGRE--VLNQPAGHLEPAESLLEAALRETLEETG 58
Cdd:cd24156  10 ILDDDHLLLIREYAAGTEryELGFPKGLIDPGETPEEAANRELKEEIG 57

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: 38.91 E-value: 1.87e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15597821   5 PHVTVATIVEDQGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIY 70
Cdd:cd18891   1 PKVDVRAFIQNENKVLLVQDKHTKEWAL--PGGFAEVGLSPKENILKEVKEETGLHVEVERLLAVF 64

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

Pssm-ID: 467588 [Multi-domain] Cd Length: 121 Bit Score: 39.11 E-value: 1.89e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  16 QGRFLLVeeQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVE---LSAVTgiylyTAPSNGVTYQRVCFAARPVR 92
Cdd:cd18876  11 AGRVLLV--KPTYKDGWELPGGVVEAGESPLQAARREVREELGLDVPvgrLLAVD-----WVPPAGGGDDAVLFVFDGGV 83

                        90       100
                ....*....|....*....|....*...
gi 15597821  93 HHPERA----LDDG-IIGPRWLTRDELA 115
Cdd:cd18876  84 LTPEQAaairLQDEeLSAYRFVTPEEAA 111

NADH pyrophosphatase; NADH pyrophosphatase, also known as NUDIX (nucleoside diphosphate linked moiety X)) motif 13/Nudt13, is thought to have NADH pyrophosphatase activity, be involved in NADH metabolic process and NADP catabolic process, catalyzing the cleavage of NADH into reduced nicotinamide mononucleotide (NMNH) and AMP, and located in mitochondrion. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity. Members of this family are also recognized by the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. A block of 8 conserved amino acids downstream of the NUDIX motif is thought to give NADH pyrophosphatase its specificity for NADH. NADH pyrophosphatase forms a dimer.

Pssm-ID: 467535 [Multi-domain] Cd Length: 126 Bit Score: 39.01 E-value: 1.91e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  36 AGHLEPAESLLEAALRETLEETGweVELSAVTgiYLYTAPsngVTYQR---VCFAARpVRHHPERALDDGIIGPRWLTRD 112
Cdd:cd03429  32 AGFVEPGETLEEAVRREVKEEVG--LRVKNVR--YVGSQP---WPFPSslmLGFTAE-ADSGEITVDDDELEDARWFSRD 103


                ....
gi 15597821 113 ELAA 116
Cdd:cd03429 104 ELPE 107

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

Pssm-ID: 467571 Cd Length: 145 Bit Score: 39.00 E-value: 2.78e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15597821   6 HVTVATIVEDQGRFLLV---EEQADGREVLNQPAGH-LEPAESLLEAALRETLEETGWEVELSAVTGI 69
Cdd:cd04689   2 HIARAIVVDDQNRFYFVvvvRDDDFGKGTLIETAGGgVEENENLEEAIRRELKEELGVEVDILCKIGI 69

adenosine nucleotide hydrolase NudE; Provisional

Pssm-ID: 183303 Cd Length: 185 Bit Score: 38.63 E-value: 4.92e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 15597821   13 VEDQGRFLLVEEQADGRE--VLNQPAGHLEPAESLLEAALRETLEETG 58
Cdd:PRK11762  55 ILDDDTLLLIREYAAGTEryELGFPKGLIDPGETPLEAANRELKEEVG 102

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: 37.92 E-value: 4.99e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   3 WHPHVTVAtIVEDQGRFLLVEEQADGREVlnQP-------AGHLEPAESLLEAALRETLEETGWEVELSAVtgIYLYTAP 75
Cdd:cd04692  25 WHRTVHVW-LVNPEEGRLLLQKRSANKDD--FPglwdisaAGHIDAGETYEEAAVRELEEELGLTVSPEDL--IFLGVIR 99


                .
gi 15597821  76 S 76
Cdd:cd04692 100 E 100

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: 37.78 E-value: 5.25e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15597821   5 PHVTVATIVEDQGRFLLVEEQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIY 70
Cdd:cd18884   8 PIPVVAAIVEHDGHIVLARNKAWPEGWYGLVTGFLEAGESPEEAVLREVKEELGLDGHEAKFIGHY 73

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: 37.97 E-value: 5.66e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  10 ATIVEDQGRFLLVEE-----QADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPsNGVTYQRV 84
Cdd:cd04700  18 VVLLNERGDILLVQEkgisgHPEKAGLWHIPSGAVEDGENPQDAAVREACEETGLRVRLVKFLGAYLGRFP-DGVLVLRH 96


                ....*.
gi 15597821  85 CFAARP 90
Cdd:cd04700  97 VWLAEP 102

nudix hydrolase

Pssm-ID: 215184 [Multi-domain] Cd Length: 144 Bit Score: 37.92 E-value: 6.91e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 15597821   35 PAGHLEPAESLLEAALRETLEETGWEVE----LSAVTGIYLYTA-PSNGVT 80
Cdd:PLN02325  39 PGGHLEFGESFEECAAREVKEETGLEIEkielLTVTNNVFLEEPkPSHYVT 89

MutT homolog-1 and similar proteins; MutT homolog-1 (MTH1), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 1/Nudt1, is a member of the NUDIX hydrolase superfamily. MTH1, the mammalian counterpart of MutT, hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-ATP, to monophosphates, thereby preventing the incorporation of such oxygen radicals during replication. This is an important step in the repair mechanism in genomic and mitochondrial DNA. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity, and contain the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. MTH1 is predominantly localized in the cytoplasm and mitochondria. Structurally, this enzyme adopts a similar fold to MutT despite low sequence similarity outside the conserved NUDIX motif. The most distinctive structural difference between MutT and MTH1 is the presence of a beta-hairpin, which is absent in MutT. This results in a much deeper and narrower substrate binding pocket. Mechanistically, MTH1 contains dual specificity for nucleotides that contain 2-OH-adenine bases and those that contain 8-oxo-guanine bases.

Pssm-ID: 467594 Cd Length: 136 Bit Score: 37.45 E-value: 8.25e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15597821   7 VTVATIVEDQGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEV 61
Cdd:cd18883   1 YTARGVIISDEHLLLARVKGDDKTFL--PGGHIEIGESAEIALVRELREELGLSC 53

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: 36.77 E-value: 1.34e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15597821  15 DQGRFLlVEEQADGREVLNQPAGHLEPAESLLEAALRETLEETG---WEVELSAVTGIYL-YTAPSN 77
Cdd:cd03671  13 RDGQVL-VGRRIDVPGAWQFPQGGIDEGEDPEEAALRELYEETGlspEDVEIIAETPDWLtYDLPED 78

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

Pssm-ID: 443295 [Multi-domain] Cd Length: 153 Bit Score: 36.73 E-value: 1.49e-03

                        10        20
                ....*....|....*....|....*..
gi 15597821  35 PAGHLEPAESLLEAALRETLEETGWEV 61
Cdd:COG4119  41 PKGEYEPGEDPLAAARREFAEETGVPA 67

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: 36.35 E-value: 1.63e-03

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 15597821  11 TIVEDQGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETG 58
Cdd:cd04666   9 RITKGELEVLLITSRKTGRWIL--PKGGPEKGETPAEAAAREAWEEAG 54

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: 36.13 E-value: 2.02e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   5 PHVTVATIVEDQGRFLLVEE-QADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPSNGVTYQR 83
Cdd:cd04679   1 PRVGCGAAILDDGRLLLVLRlRAPEAGHWGLPGGKVDWLETVEDAVRREILEELGLEIELTRLLCVVDQIDAADGEHWVA 80

                        90       100       110
                ....*....|....*....|....*....|.
gi 15597821  84 VCFAARPVRHHPERALDDGIIGPRWLTRDEL 114
Cdd:cd04679  81 PVYLAEIFSGEPRLMEPEKHGGIGWFALDAL 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: 467570 [Multi-domain] Cd Length: 130 Bit Score: 35.99 E-value: 2.32e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   9 VATIVEDQGRFLLVEEQADGREVLnqPAGHLEPAESLLEAALRETLEETGWEVE----LSAVTGIYLYtapsNGVTYQRV 84
Cdd:cd04688   5 VAAIIIRDGKVLLARGEDDDYYRL--PGGRVEFGETSEDALVREFKEELGVEVEvvrlLFVVENFFTY----DGKPFHEI 78

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 15597821  85 CFAARPVRHHPERALDDGIIGP--------RWLTRDELA 115
Cdd:cd04688  79 GFYYLVELSDEALYEQDIFFLEedgeklefRWIPLEELD 117

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: 35.96 E-value: 3.91e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821  18 RFLLVEE------QADGR-EVLNQPAGHLEPAESLLEAALRETLEETGweVELSAVTGIYLYTaPSNGVTYQRV-CFAAR 89
Cdd:cd24155  57 EVVLIEQfrigalARDESpWLLEIVAGMIDAGETPEDVARREAEEEAG--LTLDALEPIASYY-PSPGGSTERVhLYLGL 133

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: 35.55 E-value: 4.13e-03

                        10        20
                ....*....|....*....|....*
gi 15597821  35 PAGHLEPA-ESLLEAALRETLEETG 58
Cdd:cd03426  37 PGGKREPGdESPVETALRETEEEIG 61

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

Pssm-ID: 467565 [Multi-domain] Cd Length: 123 Bit Score: 34.96 E-value: 5.01e-03

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15597821  35 PAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPSNGVTyQRVCFAAR 89
Cdd:cd04682  33 PGGGREGDETPFACVLRELREELGLALPEDRLVWERVYPSNHNPGR-QSWFFVAR 86

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: 35.21 E-value: 5.33e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15597821   5 PHVTVATIV----EDQGRFLLVEEQAD---GREVLnqPAGHLEPAESLLEAALRETLEETGwevelsaVTGIYL 71
Cdd:cd18873   1 PSVTVDCVIfgfdDGELKVLLIKRKNEpfkGGWAL--PGGFVREDETLEDAARRELREETG-------LKDIYL 65

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: 34.91 E-value: 7.12e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15597821   9 VATIVEDQGRFLLVEEQADGREVLNQPA---GHLEPAESLLEAALRETLEETGWEVELSAVT 67
Cdd:cd04696   5 VCPLIENEGCYLLCKMADDRGVFPGQWAlsgGGVEPGERIEEALRREIREELGEQLILSDIT 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: 467558 [Multi-domain] Cd Length: 118 Bit Score: 34.36 E-value: 7.35e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597821   7 VTVATIVEDQGRFLLVEEQADGREVLNQPAGHLEPAESLLEAALRETLEETGWEVELSAVTGIYLYTAPsNGVTYQRVCF 86
Cdd:cd04674   6 VVVALLPVRDGLLVIRRGIEPGHGELALPGGYIEYGETWQEAAVRELREETGVEADAAEVRLFAVRSAP-DGTLLIFGLL 84

                        90
                ....*....|....*
gi 15597821  87 AARPVRHHPERALDD 101
Cdd:cd04674  85 PERPVADLPPFAPTD 99