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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998   6 NGFVSGSDGVRRWGRFGSAGLFLVSRA----GTVLMQHRAAWTNAGGTWALPGGARDSHETAREAALREAQEETGIDVDQ 81
Cdd:cd18877     1 DGWVICACGSRHWGRHGAAGLLLFAPAedggPHVLLQHRAWWTHQGGTWALPGGARDSGETPEAAALRETEEETGLDADT 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2519143998  82 VRVVSEVVTTrVDGWTYTTVIGRCDDELEVTP-NAESEELAWVNVNNLKKLPLLSPFANSLP 142
Cdd:cd18877    81 LRVVGTHVDD-HGGWSYTTVLASAPEPLPVRPaNEESVELRWVPLDEVESLPLHPGFAASWP 141

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998   6 NGFVSGSDGVRRWGRFGSAGLFLVSRA----GTVLMQHRAAWTNAGGTWALPGGARDSHETAREAALREAQEETGIDVDQ 81
Cdd:cd18877     1 DGWVICACGSRHWGRHGAAGLLLFAPAedggPHVLLQHRAWWTHQGGTWALPGGARDSGETPEAAALRETEEETGLDADT 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2519143998  82 VRVVSEVVTTrVDGWTYTTVIGRCDDELEVTP-NAESEELAWVNVNNLKKLPLLSPFANSLP 142
Cdd:cd18877    81 LRVVGTHVDD-HGGWSYTTVLASAPEPLPVRPaNEESVELRWVPLDEVESLPLHPGFAASWP 141

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  23 SAGLFLVSRAGTVLMQHRAAWTNAGgTWALPGGARDSHETAREAALREAQEETGIDVDQVRVVSEVVTTRVDGWTYTT-- 100
Cdd:pfam00293   5 AVGVVLLNEKGRVLLVRRSKKPFPG-WWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRFPDeh 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2519143998 101 -----VIGRCDDELEVTPNAESEELAWVNVNNLKKLPLLSPFANSLP 142
Cdd:pfam00293  84 eilyvFLAEVEGELEPDPDGEVEEVRWVPLEELLLLKLAPGDRKLLP 130

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2519143998  33 GTVLMQHRAAWTNAGGTWALPGGARDSHETAREAALREAQEETGIDV 79
Cdd:TIGR00586  16 GEIIITRRADGHMFAKLLEFPGGKEEGGETPEQAVVRELEEEIGIPQ 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998   6 NGFVSGSDGVRRWGRFGSAGLFLVSRA----GTVLMQHRAAWTNAGGTWALPGGARDSHETAREAALREAQEETGIDVDQ 81
Cdd:cd18877     1 DGWVICACGSRHWGRHGAAGLLLFAPAedggPHVLLQHRAWWTHQGGTWALPGGARDSGETPEAAALRETEEETGLDADT 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2519143998  82 VRVVSEVVTTrVDGWTYTTVIGRCDDELEVTP-NAESEELAWVNVNNLKKLPLLSPFANSLP 142
Cdd:cd18877    81 LRVVGTHVDD-HGGWSYTTVLASAPEPLPVRPaNEESVELRWVPLDEVESLPLHPGFAASWP 141

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  23 SAGLFLVSRAGTVLMQHRAAwTNAGGTWALPGGARDSHETAREAALREAQEETGIDVDQVRVVSEVVTTRVDGWTYTTVI 102
Cdd:COG1051     8 AVDAVIFRKDGRVLLVRRAD-EPGKGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHPDRGHVVSVAFL 86

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2519143998 103 GRCDDElEVTPNAESEELAWVNVNNLKKLPLLSPFANSL 141
Cdd:COG1051    87 AEVLSG-EPRADDEIDEARWFPLDELPELAFTPADHEIL 124

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  23 SAGLFLVSRAGTVLMQHRAAWTNAGgTWALPGGARDSHETAREAALREAQEETGIDVDQVRVVSEVVTTRVDGWTYTT-- 100
Cdd:pfam00293   5 AVGVVLLNEKGRVLLVRRSKKPFPG-WWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRFPDeh 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2519143998 101 -----VIGRCDDELEVTPNAESEELAWVNVNNLKKLPLLSPFANSLP 142
Cdd:pfam00293  84 eilyvFLAEVEGELEPDPDGEVEEVRWVPLEELLLLKLAPGDRKLLP 130

MutT homolog 2; MutT Homolog 2 (MTH2; EC 3.6.1.9), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 15/Nudt15, may catalyze the hydrolysis of nucleoside diphosphates, triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP, and prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP. MTH2 may also play a role in DNA synthesis and cell cycle progression by stabilizing PCNA. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  25 GLFLVSRAGTVLMQHRAAWTNAGgTWALPGGARDSHETAREAALREAQEETGIDVDQVRVVSeVVTT--RVDGWTYTTVI 102
Cdd:cd04678     6 GVIVLNDDGKVLLGRRKGSHGAG-TWALPGGHLEFGESFEECAAREVLEETGLEIRNVRFLT-VTNDvfEEEGKHYVTIF 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2519143998 103 GRC----DDELEVTPNAESEELAWVNVNNLKKL-PLLSPFANSL 141
Cdd:cd04678    84 VLAevddGEPEENMEPDKCEGWEWFSWDELPPLrPLFLPLANLL 127

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  23 SAGLFLVsRAGTVLMQhRAAWTNAggtWALPGGARDSHETAREAALREAQEETGIDVD--QVRVVsEVVTTRVDGWTYTT 100
Cdd:cd04690     3 KAAVIII-KDGRLLLV-RKRGTDA---FYLPGGKREPGETPLQALVRELKEELGLDLDpdSLRFL-GTFEAPAANEPGTT 76

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2519143998 101 VIGRC---DDELEVTPNAESEELAWVNVNNLKKLPL 133
Cdd:cd04690    77 VRMTCftaDYDGEPQPAAEIEELRWLDPADPDDDRL 112

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  26 LFLVSRAGTVLMQHRAAWTNAGgTWALPGGARDSHETAREAALREAQEETGIDVDQVR---VVSEVVTTRVDGW-TYTTV 101
Cdd:cd18886     4 LCFIIRDDEVLLLNRNKKPNMG-KWNGVGGKLEPGESPEECAIREVFEETGLELEDLQlrgIVTFPSFDGGEDWlMYVFL 82

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2519143998 102 IGRCDDELeVTPNAESeELAWVNVNNLKKLPL 133
Cdd:cd18886    83 AEAFSGEL-VESDREG-ILAWVPIDWLLNLPL 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  25 GLFLVSRAGTVLMQHRAAWtnaGGTWALPGGARDSHETAREAALREAQEETGIDVDQVRVVS--EVVTTR---------- 92
Cdd:cd18874     6 GALIFNPDGKVLLVRSHKW---NDLYGIPGGKVEWGETLEEALKREVKEETGLDITDIRFILvqESINSEefhkpahfvf 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2519143998  93 VDgwtyttVIGRCDDElEVTPNAESEELAWVNVNNLKKLPLLSP 136
Cdd:cd18874    83 VD------YLARTDSS-EVVLNEEAVEYLWVEPEEALKYPLNSF 119

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  36 LMQHRAawtnaGGTWALPGGARDSHETAREAALREAQEETGIDVDQVRV-VSEVVTTRVDGWTYTTVI---GRCDDELEV 111
Cdd:cd03428    21 LLQHSY-----GGHWDFPKGHVEPGESELETALRETKEETGLTVDDLPPgFRETLTYSFKEGVEKTVVyflAELTPDVEV 95

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2519143998 112 TPNAESEELAWVNVNNLKKlplLSPFANSLPILIQ 146
Cdd:cd03428    96 KLSEEHQDYKWLPYEEALQ---LLTYENIKELLKE 127

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  48 GTWALPGGARDSHETAREAALREAQEETGIDVDQVR-VVSEVVTTRVDGWTYTTvigrCD-------DELEVTPNAESE- 118
Cdd:cd04681    31 GKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRyLCSLPNTYLYKGITYKT----CDlfftaelDEKPKLKKAEDEv 106

                          90
                  ....*....|....*.
gi 2519143998 119 -ELAWVNVNNLKKLPL 133
Cdd:cd04681   107 aELEWLDLEEIEPEKL 122

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  35 VLMQHRAAWTNAGGtWALPGGARDSHETAREAALREAQEETGID---VDQVRVVSE--------VVTTrvdgwTYTTVIG 103
Cdd:cd18873    19 VLLIKRKNEPFKGG-WALPGGFVREDETLEDAARRELREETGLKdiyLEQLGTFGDpdrdprgrVISV-----AYLALVP 92

                          90       100
                  ....*....|....*....|....*
gi 2519143998 104 rcDDELEVTPNAESEELAWVNVNNL 128
Cdd:cd18873    93 --EEDLAPKAGDDAAEARWFPVDEL 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2519143998  23 SAGLFLVSRAGTVLMQHRAAWTNAGGT-WALPGGARDSHETAREAALREAQEETGIDVDQVRVVSEVVTTRV 93
Cdd:cd04685     2 AARVLLLDPDGRVLLFRFHDPDDPGRSwWFTPGGGVEPGESPEQAAVRELREETGLRLEPDDLGGPVWRRRA 73

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  48 GTWALPGGARDSHETAREAALREAQEETGIDVDQVRVVSevVTTRVDGWTYTTVIGRC-DDELEVTPNAESEELAWVNVN 126
Cdd:cd04671    26 GKWYLPAGRVEPGESIVEAAKREVKEETGLKCEPSTLLS--VEEAGGSWYRFVFTGNItGGKLKTPADADSESLQAFWID 103

                  ....*...
gi 2519143998 127 NLK-KLPL 133
Cdd:cd04671   104 DIStKLPL 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2519143998  27 FLVSRAGTVLMQHRAAWT-NAGGTW-ALPGGARDSHETAREAALREAQEETGIDVD 80
Cdd:cd04693    35 WIFNSDGEILIQQRSPDKkGFPGMWeASTGGSVLAGETSLEAAIRELKEELGIDLD 90

putative NUDIX hydrolase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  25 GLFLVSRAGTvLMQHraawtnaGGTWALPGGARDSHETAR-EAALREAQEETGIDVDQVRVVSEVV-TTRVDGWTYTTVI 102
Cdd:PRK10707   45 TLLLTQRSIH-LRKH-------AGQVAFPGGAVDPTDASLiATALREAQEEVAIPPSAVEVIGVLPpVDSSTGYQVTPVV 116

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2519143998 103 GRCDDELEVTPNAESeelawvnVNNLKKLPLLSPFANS--LPILIQRAMH 150
Cdd:PRK10707  117 GIIPPDLPYRANEDE-------VAAVFEMPLAEALHLGryHPLDIYRRGQ 159

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  33 GTVLMQHRAawTNAGGTWALPGGARDSHETAREAALREAQEETGIDVdQVRVVSEVVTTRVD---GWTYTTVIGRCDDEl 109
Cdd:cd04699    13 GRVLLLRRS--RAGAGEWELPGGRLEPGESPEEALKREVKEETGLDV-SVGELLDTWTFELDpdkGVFIVTYLCRLVGG- 88

                          90       100
                  ....*....|....*....|....*....
gi 2519143998 110 EVTPNAESEELAWVNVNNLKKLPLLSPFA 138
Cdd:cd04699    89 EVTLSDEHEEYEWVTPEELAELELPEGYR 117

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  35 VLMQHRAAwTNAGGtWALPGGARDSHETAREAALREAQEETGIDVDQVRVVSevvttrVDGWT------YTTVIGRCDD- 107
Cdd:cd18875    16 VLVLDRVK-KDWGG-YTFPGGHVEPGESFVDSVIREVKEETGLTIKNPELCG------IKQWInpdgerYIVFLYKTDHf 87

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 2519143998 108 ELEVTPNAESeELAWVNVNNLKKLPLLSPFANSLPIL 144
Cdd:cd18875    88 SGELLSSEEG-ELFWIPIEELKKLPLATDFDEMLRVF 123

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  35 VLMQHRAAwtnagGTWALPGGARDSHETAREAALREAQEETGIDVDQVRVVSEVVTTRVDGWTYTTV----IGRCDDELe 110
Cdd:cd04665    14 LFTRHKER-----RGWEFPGGKREPGETIEEAARRELYEETGAVIFELKPLGQYSVHGKGQEFFGAVyyaeVKSFEPIL- 87

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2519143998 111 vtPNAESEELAWVnvnnlKKLPLLS-PFANSLPILIQRA 148
Cdd:cd04665    88 --PYFETAEVRLF-----DELPEFSlTYPDIQPHLLEKL 119

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2519143998  49 TWALPGGARDSHETAREAALREAQEETGIDVDQVRVVSEVVTT 91
Cdd:cd03424    30 LLELPAGKIDPGEDPEEAARRELEEETGYTAGDLELLGSFYPS 72

nudix hydrolase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  25 GLFLVsRAGTVLMQHRAAwTNAGGTWALPGGARDSHETAREAALREAQEETGIDVDQVR---VVSEVVTTRVDGWTYTTV 101
Cdd:PLN02325   13 VVFLL-KGNSVLLGRRRS-SIGDSTFALPGGHLEFGESFEECAAREVKEETGLEIEKIElltVTNNVFLEEPKPSHYVTV 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2519143998 102 IGRCD--DELEVTPNAESEELA---WVNVNNLKKlPLLSP 136
Cdd:PLN02325   91 FMRAVlaDPSQVPQNLEPEKCYgwdWYEWDNLPE-PLFWP 129

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  28 LVSRAGTVLMQHRAaWTNAGGTWALPGGARDSHETAREAALREAQEETGIDVDQVRVVSevVTTRV--DGWTYTTVIGRC 105
Cdd:cd04691     7 VVVKEGKVLLVKRA-YGPGKGRWTLPGGFVEEGETLDEAIVREVLEETGIDAKPVGIIG--VRSGVirDGKSDNYVVFLL 83

                          90
                  ....*....|....*.
gi 2519143998 106 DDeLEVTPNAESEELA 121
Cdd:cd04691    84 EY-VGGEPKPDERENS 98

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.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 2519143998  50 WALPGGARDSHETAREAALREAQEETGIDVD 80
Cdd:cd18880    27 YILPGGGQEHGETLPEALKRECLEETGLDVE 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  23 SAGLFLVSRAGTVLMQHRAAwtnaGGTWALPGGARDSHETAREAALREAQEETGIDVDQVRVVS-----EVVTTRVDG-- 95
Cdd:cd04676    19 SVAAVILNEDGRILLQRKGG----LGLWSLPAGAIEPGEHPAEAVIREVREETGLLVKPTRLLGvfggkEFRYTYPNGdq 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2519143998  96 WTYTTVIGRCdDELEVTPNA---ESEELAWVNVNNLKKLPLLSP 136
Cdd:cd04676    95 VEYTVIAFKC-VVTGGTLNAidgETSELRYFSRTQMPTLALPYP 137

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  33 GTVLMQHRaaWTNAGGTWALPGGARDSHETAREAALREAQEETGIDVD--QVRVVSEVVTTRVDGWTYTTVIG-----RC 105
Cdd:cd04669    11 DKLLLIRR--TKPGEEYYVFPGGGIEPGETPEEAALREAVEELGLDVAvtLITLILRVLNDGTQHYFLARVITgsfglGT 88

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2519143998 106 DDELEvTPNAESEELAWVNVNNLKKLPLLSP 136
Cdd:cd04669    89 GPEFE-RPERGTYEPVWVPLTALPALNLRPP 118

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  50 WALPGGARDSHETAREAALREAQEETGIDVDQ-VRVVS-----------EVVTTRVDGWTYTTVIgrcddelevTPNAES 117
Cdd:cd04680    25 WYLPGGGVDKGETAEEAARRELREEAGVVLTGpPRLFGvyfnrrvsprdHVALYRVREFEQTEPP---------EPNGEI 95

                          90
                  ....*....|.
gi 2519143998 118 EELAWVNVNNL 128
Cdd:cd04680    96 AEAGFFALDAL 106

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  27 FLVSRAGTVLMQHRAA---WtnaGGTWALPGGARDSHETAREAALREAQEETGIDVDQVRVVSEVVTTRVdgWTYTTVIG 103
Cdd:cd03431     9 LVLRDGGRVLLEKRPEkglL---AGLWEFPLVETEEEEEEAEALLGLLAEELLLILEPLGEVKHVFSHFR--LHITVYLV 83

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2519143998 104 RCDDElevtPNAESEELAWVNVNNLKKLPLLSPFAN 139
Cdd:cd03431    84 ELPEA----PPAAPDEGRWVDLEELDEYALPAPMRK 115

Antisense Basic Fibroblast Growth Factor; Antisense Basic Fibroblast Growth Factor (ASFGF2; EC 3.6.1.-), also known as nucleoside diphosphate-linked moiety X)) motif 6/Nudt6, and similar proteins including peroxisomal coenzyme A diphosphatase/Nudt7 and mitochondrial coenzyme A diphosphatase/Nudt8. The Nudt6 gene overlaps and lies on the opposite strand from FGF2 gene, and is thought to be the FGF2 antisense gene. The two genes are independently transcribed, and their expression shows an inverse relationship, suggesting that this antisense transcript may regulate FGF2 expression. This gene has also been shown to have hormone-regulatory and antiproliferative actions in the pituitary that are independent of FGF2 expression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 2519143998  48 GTWALPGGARDSHETAREAALREAQEETGIDVDQVRVVS 86
Cdd:cd04670    27 GGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILG 65

RNA pyrophosphohydrolase; Reviewed

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2519143998  25 GLFLVSRAGTVLMQHRAAWTNAggtWALPGGARDSHETAREAALREAQEETGIDVDQVRVVSE 87
Cdd:PRK00714   12 GIILLNRQGQVFWGRRIGQGHS---WQFPQGGIDPGETPEQAMYRELYEEVGLRPEDVEILAE 71

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2519143998  61 ETAREAALREAQEETGIDVDQVRVVSevvttrVDGWTYTTV-----IGRCDDELEVTPNAESEELAWVNVNNLKKLPLLS 135
Cdd:cd03429    39 ETLEEAVRREVKEEVGLRVKNVRYVG------SQPWPFPSSlmlgfTAEADSGEITVDDDELEDARWFSRDELPEALFLP 112

                          90
                  ....*....|....
gi 2519143998 136 PfanslPILIQRAM 149
Cdd:cd03429   113 P-----PGSIARRL 121

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