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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 158 HRVGIGAFVINHNKEVLVVQEKTGrfqGQGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAFRQTHKAFFGKS 237
Cdd:cd04670     1 HQVGVGGLVINENNEVLVVQEKYG---GPGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFRHQHPGRFGKS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1063736742 238 DLFFVCMLKPLS-LEINAQESEIEAAQWMPWEEYINQPFVQNY 279
Cdd:cd04670    78 DLYFVCRLRPLSdEEIKICPEEIAEAKWMPLEEYLKQPNVSQI 120

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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 158 HRVGIGAFVINHNKEVLVVQEKTGrfqGQGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAFRQTHKAFFGKS 237
Cdd:cd04670     1 HQVGVGGLVINENNEVLVVQEKYG---GPGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFRHQHPGRFGKS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1063736742 238 DLFFVCMLKPLS-LEINAQESEIEAAQWMPWEEYINQPFVQNY 279
Cdd:cd04670    78 DLYFVCRLRPLSdEEIKICPEEIAEAKWMPLEEYLKQPNVSQI 120

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 158 HRVGIGAFVINHNKEVLVVQEKTGRFQGQgiWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAFRQ---THKAFF 234
Cdd:pfam00293   2 RRVAVGVVLLNEKGRVLLVRRSKKPFPGW--WSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHylaPFDGRF 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1063736742 235 GKSDLFFVCMLKPLSLEINAQ-ESEIEAAQWMPWEEYINQPFVQ-NYELLRYM 285
Cdd:pfam00293  80 PDEHEILYVFLAEVEGELEPDpDGEVEEVRWVPLEELLLLKLAPgDRKLLPWL 132

RNA pyrophosphohydrolase; Reviewed

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063736742 150 DTLPanasHRVGIGAFVINHNKEVLVVQektgRFQGQGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILA 225
Cdd:PRK00714    3 DDDG----YRPNVGIILLNRQGQVFWGR----RIGQGHSWQFPQGGIDPGETPEQAMYRELYEEVGLRPEDVEILA 70

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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 158 HRVGIGAFVINHNKEVLVVQEKTGrfqGQGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAFRQTHKAFFGKS 237
Cdd:cd04670     1 HQVGVGGLVINENNEVLVVQEKYG---GPGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFRHQHPGRFGKS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1063736742 238 DLFFVCMLKPLS-LEINAQESEIEAAQWMPWEEYINQPFVQNY 279
Cdd:cd04670    78 DLYFVCRLRPLSdEEIKICPEEIAEAKWMPLEEYLKQPNVSQI 120

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 1063736742 160 VGIGAFVINHNKeVLVVQEKTGRFQGQgiWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAFRqTHKAFFGKSDL 239
Cdd:cd04691     2 LGVGGVVVKEGK-VLLVKRAYGPGKGR--WTLPGGFVEEGETLDEAIVREVLEETGIDAKPVGIIGVR-SGVIRDGKSDN 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1063736742 240 FFVCMLKPLSLEINAQESEIEAAQWMPWEEYINQPFVQNyeLLRYMT 286
Cdd:cd04691    78 YVVFLLEYVGGEPKPDERENSEAGFLTLEEALANEDIAD--MSRELI 122

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 160 VGIGAFVINHNKEVLVVQEKTGRFQGQgiWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAFRQTHKAFFGKSDL 239
Cdd:cd02883     1 VAVGAVVFDDEGRVLLVRRSDGPGPGG--WELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEGRHVV 78

                          90       100
                  ....*....|....*....|....*...
gi 1063736742 240 FFVCMLKPLSLEI-NAQESEIEAAQWMP 266
Cdd:cd02883    79 VLVFLARVVGGEPpPLDDEEISEVRWVP 106

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 159 RVGIGAFVINHNKEVLVVQEKTGRFQGqGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAFRQTHKAFFGKSD 238
Cdd:COG0494    13 RPAVVVVLLDDDGRVLLVRRYRYGVGP-GLWEFPGGKIEPGESPEEAALRELREETGLTAEDLELLGELPSPGYTDEKVH 91

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1063736742 239 LFFVCMLKPLSLEINAQESEIEAAQWMPWEE 269
Cdd:COG0494    92 VFLARGLGPGEEVGLDDEDEFIEVRWVPLDE 122

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 149 DDTLPANASHRVgIGAFVINHNKEVLVVQ---EKTGRfqgQGIWKF-PTGVVNEGEDIHDGSVREVKEETGVDTEFDQIL 224
Cdd:cd04693    20 GEPLPEGEYHLV-VHVWIFNSDGEILIQQrspDKKGF---PGMWEAsTGGSVLAGETSLEAAIRELKEELGIDLDADELR 95

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063736742 225 AFRQTHK--AFFgksDLFFVCmlKPLSLE-INAQESEIEAAQWMPWEEYINqpFVQNYELLRY 284
Cdd:cd04693    96 PILTIRFdnGFD---DIYLFR--KDVDIEdLTLQKEEVQDVKWVTLEEILE--MIESGEFIPY 151

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 1063736742 168 NHNKEVLVVQEKTGRFqgqgiWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQIlAFRQTHKAFFGKSDL----FFVC 243
Cdd:cd03428    14 NGEIEFLLLQHSYGGH-----WDFPKGHVEPGESELETALRETKEETGLTVDDLPP-GFRETLTYSFKEGVEktvvYFLA 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1063736742 244 MLKPlSLEINAQEsEIEAAQWMPWEEYINQpfvQNYELLR 283
Cdd:cd03428    88 ELTP-DVEVKLSE-EHQDYKWLPYEEALQL---LTYENIK 122

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 1063736742 159 RVGIGAFVINHNKeVLVVQEKTGRfqgqGI-WKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAFRQT--HKAFFG 235
Cdd:cd18880     1 RIRAKAIIIEDGK-LLLVKHRDEG----GIfYILPGGGQEHGETLPEALKRECLEETGLDVEVGDLLFVREYigPNKPVH 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1063736742 236 KSDLFFVCMLKPLSLEI-NAQESEIEAAQWMPWEEYINQPF 275
Cdd:cd18880    76 QVELFFLCTLEGGELTLgSDPDLNQVGVEWIPLEELDSIRL 116

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 159 RVGIGAFVInHNKEVLVVQEktGRFQGQGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAFRQ-THKAFFGKS 237
Cdd:cd04673     1 IVAVGAVVF-RDGRVLLVRR--GNPPDAGLWSFPGGKVELGETLEDAALRELREETGLEAEVVGLLTVVDvIERDEAGRV 77

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1063736742 238 D-----LFFVCmlKPLSLEINAqESEIEAAQWMPWEE 269
Cdd:cd04673    78 RfhyviLDFLA--EWVSGEPVA-GDDALDARWFSLEE 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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 160 VGIGAFVINHNKEVLVVQE--KTGrfqgqgiWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILA--FRQTHKAFFG 235
Cdd:cd18876     1 AAAGALFTDAAGRVLLVKPtyKDG-------WELPGGVVEAGESPLQAARREVREELGLDVPVGRLLAvdWVPPAGGGDD 73

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1063736742 236 KSD-LFFVCMLKPLSLE-INAQESEIEAAQWMPWEE 269
Cdd:cd18876    74 AVLfVFDGGVLTPEQAAaIRLQDEELSAYRFVTPEE 109

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1063736742 163 GAFVINHN-KEVLVVQEKTGRFQgqgiWKFPTGVVNEGEDIHDGSVREVKEETGVD 217
Cdd:cd03672     5 GAILLNEDlDKVLLVKGWKSNSS----WGFPKGKINKDESDADCAIREVYEETGFD 56

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063736742 160 VGIGAFVINHNKEVLVVQEK-TGRfqgqgiWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILA 225
Cdd:cd18879    19 PGVTAVVLRDAGRVLLVRRAdNGR------WTPVTGIVEPGEQPADAAVREVLEETGVDVEVERLAS 79

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 1063736742 166 VINHNKEVLVVQEKTgrfQGQGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQIL---AFR--QTHKAFFgksdLF 240
Cdd:cd04699     8 VIFDNGRVLLLRRSR---AGAGEWELPGGRLEPGESPEEALKREVKEETGLDVSVGELLdtwTFEldPDKGVFI----VT 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1063736742 241 FVCMLKPLSLEINaqeSEIEAAQWMPWEEYINQPFVQNYE 280
Cdd:cd04699    81 YLCRLVGGEVTLS---DEHEEYEWVTPEELAELELPEGYR 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 1063736742 174 LVVQEKTGRFQGQ----------GIWK-FPTGVVNEGEDIHDGSVREVKEETGVD----TEFDQILaFRQTHKAFFGKsd 238
Cdd:cd04697    31 IVVRNAAGRLLVQkrtmdkdycpGYLDpATGGVVGAGESYEENARRELEEELGIDgvplRPLFTFY-YEDDRSRVWGA-- 107

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1063736742 239 LFFVCMLKPLSLeinaQESEIEAAQWMPWEE 269
Cdd:cd04697   108 LFECVYDGPLKL----QPEEVAEVDWMSEDE 134

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 1063736742 166 VINHNKEVLVVQEKTGRFQGqgiWKFPTGVVNEGEDIHDGSVREVKEETGVD 217
Cdd:cd18875     9 IYDGEDRVLVLDRVKKDWGG---YTFPGGHVEPGESFVDSVIREVKEETGLT 57

RNA pyrophosphohydrolase; Reviewed

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063736742 150 DTLPanasHRVGIGAFVINHNKEVLVVQektgRFQGQGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILA 225
Cdd:PRK00714    3 DDDG----YRPNVGIILLNRQGQVFWGR----RIGQGHSWQFPQGGIDPGETPEQAMYRELYEEVGLRPEDVEILA 70

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 166 VINHNKEVLVVQEKTGRfqgqgiWKFPTGVVNEGEDIHDGSVREVKEETGVDT-EFDQILAFRQTHKAFF 234
Cdd:cd04667     6 ICRRGDRILLVARRGGR------WLLPGGKIEPGESPLEAAIRELKEETGLAAlSLLYLFEHEGPHKLHH 69

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 160 VGIGAFVINHNKeVLVVQEKTGrfqgqGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAFRQTHK-----AFF 234
Cdd:cd04672     3 VDVRAAVFKDGK-ILLVREKSD-----GRWTLPGGWADVGLSPAENAVKEVREESGYEVRARKLLAVFDRNKgghppSPF 76

                          90       100       110
                  ....*....|....*....|....*....|
gi 1063736742 235 GKSDLFFVCMLKPlslEINAQESEIEAAQW 264
Cdd:cd04672    77 HVYKLFFLCELIG---GEAQTSIETSEVGF 103

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1063736742 164 AFVINHNKEVLVVQEKTGrFqGQGIWKFPTGVVNEGEDIHDGSVREVKEETGV 216
Cdd:cd03427     6 VFVLRGDDRVLLGLKKRG-F-GAGKWNGFGGKVEPGETIEEAAVRELEEEAGL 56

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 165 FVINHNKEVLVVQektgRFQGQGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTefDQILAFRQTHKAFFGKSD------ 238
Cdd:cd04664     8 YRKDEEGEVLLLK----RTDDGGFWQSVTGGIEDGETPWQAALRELKEETGLDP--LELQLIDLNVSNFYEIFDdwrpgv 81

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1063736742 239 ------LFFVCMLKPLSLEINAqesEIEAAQWMPWEE 269
Cdd:cd04664    82 tvntehVFAVEVPEEQPIRLSP---EHTDYRWLPYEE 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 161 GIGAFVINHNKEVLVVQEKTGRFqgqgiWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQIL--AFRQTHkafFGKSD 238
Cdd:cd04680     2 GVRAIVLDDAGRVLLVRHTYVPG-----WYLPGGGVDKGETAEEAARRELREEAGVVLTGPPRLfgVYFNRR---VSPRD 73

                          90       100       110
                  ....*....|....*....|....*....|
gi 1063736742 239 --LFFVCMLKPLSLEINAQeSEIEAAQWMP 266
Cdd:cd04680    74 hvALYRVREFEQTEPPEPN-GEIAEAGFFA 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1063736742 162 IGAFVINHNKEVLVVQEKTGRfqgqGIWKFPTGVVNEGEDIHDGSVREVKEETGVD 217
Cdd:cd18874     5 VGALIFNPDGKVLLVRSHKWN----DLYGIPGGKVEWGETLEEALKREVKEETGLD 56

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 159 RVGIGAFVINHNKEVLVVQEKTgrfqgQGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAF--RQTH---KAF 233
Cdd:cd18890     2 KVDIRAVVFNDKEEILLVKEKE-----DGKWTLPGGWADVGYTPTEVAAKEVEEETGLEVSPKKLLAIldKRKHphpPQP 76

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1063736742 234 FGKSDLFFVCMLKPLSLeinAQESEIEAAQW 264
Cdd:cd18890    77 TYVYKLFILCEIEGGEL---KPSFETGEVRF 104

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063736742 164 AFVINHNKeVLVVQEKtgrfqGQGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAFRQTHK 231
Cdd:cd18891     7 AFIQNENK-VLLVQDK-----HTKEWALPGGFAEVGLSPKENILKEVKEETGLHVEVERLLAVFDTDL 68

Nudix family hydrolase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 159 RVGIGAFVI-NHNKEVLVVQEKTGRFQGqGIWKFPTGVVNEGEDIHDGSVREVKEETGVD 217
Cdd:PRK08999    4 RIHVAAGVIrDADGRILLARRPEGKHQG-GLWEFPGGKVEPGETVEQALARELQEELGIE 62

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 158 HRVGIGAFVINHNKEVLVVQEK---TGRFqgqgIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQILAfrqthkAFF 234
Cdd:cd03424     1 HPGAVAVLAITDDGKVVLVRQYrhpVGRV----LLELPAGKIDPGEDPEEAARRELEEETGYTAGDLELLG------SFY 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1063736742 235 ---GKSD---LFFVCMLKPLSLEINAQESEIEAAQWMPWEE 269
Cdd:cd03424    71 pspGFSDeriHLFLAEDLTPVSEQALDEDEFIEVVLVPLEE 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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 166 VINHNKEVLVVQEKTGRFQGQGIWKFPTGVVNEGEDIHDGSVREVKEETGVDTEFDQIL---AFRQTHKAFFGKSDL--- 239
Cdd:cd04685     7 LLDPDGRVLLFRFHDPDDPGRSWWFTPGGGVEPGESPEQAAVRELREETGLRLEPDDLGgpvWRRRAVFDFSGETVRqde 86

                          90       100       110
                  ....*....|....*....|....*....|
gi 1063736742 240 -FFVcmlkplsleINAQESEIEAAQWMPWE 268
Cdd:cd04685    87 rFFL---------VRVPAFEVDTAGWTDLE 107

NUDIX hydrolase YfcD; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063736742 194 GVVNEGEDIHDGSVREVKEETGV-DTEFdqilafrQTHKAFFGKSD-------LFFVCMLKPLSLeinaQESEIEAAQWM 265
Cdd:PRK15393   73 GVVQAGEQLLESARREAEEELGIaGVPF-------AEHGQFYFEDEncrvwgaLFSCVSHGPFAL----QEEEVSEVCWM 141

                  ....
gi 1063736742 266 PWEE 269
Cdd:PRK15393  142 TPEE 145