NAD(+) diphosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614   1 MDRIIEKSDLGWWIVSHEQKLWLPGGEIPYGAADIFDLVGQPALRIGEWQGDPVWLIQQA--RRQDMGSVRQVLDRDVGL 78
Cdd:PRK00241    3 MRRDLEALDAGWWVVSHEQQLWLPDGELPFGAAANLDLPGLRALQIGEWQGEPVWLVRQDplRGHEMGSLRQLLDLDDGL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614  79 FQLAGRGVQLAEFYRSHKYCGYCGHTMHPSKTEWAMLCGHCRERYYPQIAPCIIVAIRRDDSILLAQHTRHRNGIHTVLA 158
Cdd:PRK00241   83 FQLLGRAVQLAEFYRSHRFCGYCGHPMHPSKTEWAMLCPHCRERYYPRIAPCIIVAVRRGDEILLARHPRHRNGVYTVLA 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614 159 GFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPMSLMTAFMAEYDSGEIVIDQKELLEANWYRYDDLPLLPPPG 238
Cdd:PRK00241  163 GFVEVGETLEQCVAREVMEESGIKVKNLRYVGSQPWPFPHSLMLGFHADYDSGEIVFDPKEIADAQWFRYDELPLLPPSG 242

                         250
                  ....*....|....
gi 1043698614 239 TVARRLIEDTVAMC 252
Cdd:PRK00241  243 TIARRLIEDTVALC 256

NAD(+) diphosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614   1 MDRIIEKSDLGWWIVSHEQKLWLPGGEIPYGAADIFDLVGQPALRIGEWQGDPVWLIQQA--RRQDMGSVRQVLDRDVGL 78
Cdd:PRK00241    3 MRRDLEALDAGWWVVSHEQQLWLPDGELPFGAAANLDLPGLRALQIGEWQGEPVWLVRQDplRGHEMGSLRQLLDLDDGL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614  79 FQLAGRGVQLAEFYRSHKYCGYCGHTMHPSKTEWAMLCGHCRERYYPQIAPCIIVAIRRDDSILLAQHTRHRNGIHTVLA 158
Cdd:PRK00241   83 FQLLGRAVQLAEFYRSHRFCGYCGHPMHPSKTEWAMLCPHCRERYYPRIAPCIIVAVRRGDEILLARHPRHRNGVYTVLA 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614 159 GFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPMSLMTAFMAEYDSGEIVIDQKELLEANWYRYDDLPLLPPPG 238
Cdd:PRK00241  163 GFVEVGETLEQCVAREVMEESGIKVKNLRYVGSQPWPFPHSLMLGFHADYDSGEIVFDPKEIADAQWFRYDELPLLPPSG 242

                         250
                  ....*....|....
gi 1043698614 239 TVARRLIEDTVAMC 252
Cdd:PRK00241  243 TIARRLIEDTVALC 256

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 1043698614 128 APCIIVAIRRD-DSILLAQHTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPMSLMTAFMA 206
Cdd:cd03429     1 DPAVIVLVTNGeDKILLARQPRWPPGRYSLLAGFVEPGETLEEAVRREVKEEVGLRVKNVRYVGSQPWPFPSSLMLGFTA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1043698614 207 EYDSGEIVIDQKELLEANWYRYDDLP---LLPPPGTVARRLIED 247
Cdd:cd03429    81 EADSGEITVDDDELEDARWFSRDELPealFLPPPGSIARRLIRA 124

nudix-type nucleoside diphosphatase, YffH/AdpP family; Members of this family include proteins of about 200 amino acids, including the recently characterized nudix hydrolase YffH, shows to be highly active as a GDP-mannose pyrophosphatase. It also includes the C-terminal half of a 361-amino acid protein, TrgB from Rhodobacter sphaeroides, shown experimentally to help confer tellurite resistance. This model also hits a region near the C-terminus of a 1092-amino acid protein of C. elegans. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614 136 RRDDSILLAQ------HTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTsQPWPFP---MSLMTAFMA 206
Cdd:TIGR00052  55 KKDTVVLIEQfriaayVNGEEPWLLELSAGMVEKGESPEDVARREAIEEAGYQVKNLRKLL-SFYMSPggvTELIHLFIA 133

                  ....
gi 1043698614 207 EYDS 210
Cdd:TIGR00052 134 EVDD 137

NAD(+) diphosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614   1 MDRIIEKSDLGWWIVSHEQKLWLPGGEIPYGAADIFDLVGQPALRIGEWQGDPVWLIQQA--RRQDMGSVRQVLDRDVGL 78
Cdd:PRK00241    3 MRRDLEALDAGWWVVSHEQQLWLPDGELPFGAAANLDLPGLRALQIGEWQGEPVWLVRQDplRGHEMGSLRQLLDLDDGL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614  79 FQLAGRGVQLAEFYRSHKYCGYCGHTMHPSKTEWAMLCGHCRERYYPQIAPCIIVAIRRDDSILLAQHTRHRNGIHTVLA 158
Cdd:PRK00241   83 FQLLGRAVQLAEFYRSHRFCGYCGHPMHPSKTEWAMLCPHCRERYYPRIAPCIIVAVRRGDEILLARHPRHRNGVYTVLA 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614 159 GFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPMSLMTAFMAEYDSGEIVIDQKELLEANWYRYDDLPLLPPPG 238
Cdd:PRK00241  163 GFVEVGETLEQCVAREVMEESGIKVKNLRYVGSQPWPFPHSLMLGFHADYDSGEIVFDPKEIADAQWFRYDELPLLPPSG 242

                         250
                  ....*....|....
gi 1043698614 239 TVARRLIEDTVAMC 252
Cdd:PRK00241  243 TIARRLIEDTVALC 256

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 1043698614 128 APCIIVAIRRD-DSILLAQHTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPMSLMTAFMA 206
Cdd:cd03429     1 DPAVIVLVTNGeDKILLARQPRWPPGRYSLLAGFVEPGETLEEAVRREVKEEVGLRVKNVRYVGSQPWPFPSSLMLGFTA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1043698614 207 EYDSGEIVIDQKELLEANWYRYDDLP---LLPPPGTVARRLIED 247
Cdd:cd03429    81 EADSGEITVDDDELEDARWFSRDELPealFLPPPGSIARRLIRA 124

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 1043698614 137 RDDSILLAQHTRHRN-GIHTVLAGFVEVGETLEQAVAREVMEESGI--KVKNLRYVTSQPWPFPMS-LMTAFMAEYDSGE 212
Cdd:cd04691    10 KEGKVLLVKRAYGPGkGRWTLPGGFVEEGETLDEAIVREVLEETGIdaKPVGIIGVRSGVIRDGKSdNYVVFLLEYVGGE 89

                          90
                  ....*....|....*....
gi 1043698614 213 IVIDQKELLEANWYRYDDL 231
Cdd:cd04691    90 PKPDERENSEAGFLTLEEA 108

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614 123 YYPQIAPCIIVAIRRDDSILLAqhTRHRN---GIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPMS 199
Cdd:cd04681     1 YFHNVAAAVGVIIRNEGEILFV--RRAKEpgkGKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYLCSLPNTYLYK 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1043698614 200 LMTA------FMAEYDS-GEIVIDQKELLEANWYRYDDLPLLP 235
Cdd:cd04681    79 GITYktcdlfFTAELDEkPKLKKAEDEVAELEWLDLEEIEPEK 121

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614 131 IIVAIRRDDSILLAQHTRHRNGIHTVL--AGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWP-FPMSLMTAFMAE 207
Cdd:COG0494    17 VVVLLDDDGRVLLVRRYRYGVGPGLWEfpGGKIEPGESPEEAALRELREETGLTAEDLELLGELPSPgYTDEKVHVFLAR 96

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1043698614 208 Y---DSGEIVIDQKELLEANWYRYDDLPLLPPPGTVARRLIE 246
Cdd:COG0494    97 GlgpGEEVGLDDEDEFIEVRWVPLDEALALVTAGEIAKTLAA 138

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 1043698614 125 PQIAPCIIVAIRRDDSILLAQHtRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLR----------YVTsqpw 194
Cdd:cd04677     9 PLILVGAAVIILNEQGRILLQK-RTDTGDWGLPGGAMELGESLEETARREVFEETGLTVEELEllgvysgkdlYYT---- 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1043698614 195 pFP-----MSLMTAFMAEYDSGEIVIDQKELLEANWYRYDDLP-LLPPPgtvARRLIE 246
Cdd:cd04677    84 -YPngdevYNVTAVYLVRDVSGELKVDDEESLELRFFSLDELPeNINPQ---HRDVIE 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 1043698614 129 PCIIVAIRRDDSILLAQHTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPMS-------LM 201
Cdd:cd18874     3 PTVGALIFNPDGKVLLVRSHKWNDLYGIPGGKVEWGETLEEALKREVKEETGLDITDIRFILVQESINSEEfhkpahfVF 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1043698614 202 TAFMAEYDSGEiVIDQKELLEANWYR---YDDLPLlpppGTVARRLIE 246
Cdd:cd18874    83 VDYLARTDSSE-VVLNEEAVEYLWVEpeeALKYPL----NSFTRLLLE 125

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 1043698614 131 IIVAIRRDDSILLAQhtRHRN---GIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVT---------SQPWPFPM 198
Cdd:cd04673     4 VGAVVFRDGRVLLVR--RGNPpdaGLWSFPGGKVELGETLEDAALRELREETGLEAEVVGLLTvvdvierdeAGRVRFHY 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1043698614 199 sLMTAFMAEYDSGEIVIDQkELLEANWYRYDDLPLLP-PPGTvaRRLIE 246
Cdd:cd04673    82 -VILDFLAEWVSGEPVAGD-DALDARWFSLEELDGLPlTPGT--RDVLE 126

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1043698614 130 CIIVAIRRDDSILLAQHTRHrnGIHTVL----AGFVEVGETLEQAVAREVMEESGIKVKNLRYVTS 191
Cdd:cd03424     5 VAVLAITDDGKVVLVRQYRH--PVGRVLlelpAGKIDPGEDPEEAARRELEEETGYTAGDLELLGS 68

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1043698614 135 IRRDDSILLAQHtRHRNGIHTVL-AGFVEVGETLEQAVAREVMEESGIKVK 184
Cdd:cd18880     8 IIEDGKLLLVKH-RDEGGIFYILpGGGQEHGETLPEALKRECLEETGLDVE 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 1043698614 133 VAIRRDDSILLAQHTrHRNGIHtVLAGFVEVGETLEQAVAREVMEESGIKvknlryVTSQPWPFPMSLMTAFMA------ 206
Cdd:cd04680     6 IVLDDAGRVLLVRHT-YVPGWY-LPGGGVDKGETAEEAARRELREEAGVV------LTGPPRLFGVYFNRRVSPrdhval 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1043698614 207 ----EYDSGEIVIDQKELLEANWYRYDDLPLLPPPGTvARRLIE 246
Cdd:cd04680    78 yrvrEFEQTEPPEPNGEIAEAGFFALDALPEDTTPAT-RRRLAE 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 1043698614 159 GFVEVGETLEQAVAREVMEESGIKVK-----NLRyvTSQPWPFPMS------LMTAfmaeYDSGEIVIDQKELLEANWYR 227
Cdd:cd04670    34 GLVDPGEDIGEAAVREVFEETGIDTEfvsilGFR--HQHPGRFGKSdlyfvcRLRP----LSDEEIKICPEEIAEAKWMP 107

                  ....
gi 1043698614 228 YDDL 231
Cdd:cd04670   108 LEEY 111

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 1043698614 131 IIVAIRRDDSILLAQHtRHRNGIHTVlAGFVEVGETLEQAVAREVMEESGIKVKNLRY-----VTSQPWPFPMSLMTA-- 203
Cdd:cd04665     3 VVVIARYKGKWLFTRH-KERRGWEFP-GGKREPGETIEEAARRELYEETGAVIFELKPlgqysVHGKGQEFFGAVYYAev 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1043698614 204 --FMAEYDSGEI--VIDQKELLEANWYRYDDLPLL 234
Cdd:cd04665    81 ksFEPILPYFETaeVRLFDELPEFSLTYPDIQPHL 115

nudix hydrolase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614 125 PQIApcIIVAIRRDDSILLAQHtRHRNGIHT--VLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTS-----QPWPFP 197
Cdd:PLN02325    8 PRVA--VVVFLLKGNSVLLGRR-RSSIGDSTfaLPGGHLEFGESFEECAAREVKEETGLEIEKIELLTVtnnvfLEEPKP 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1043698614 198 MSLMTAFMAeydsgEIVIDQKEL---LEA------NWYRYDDLPL 233
Cdd:PLN02325   85 SHYVTVFMR-----AVLADPSQVpqnLEPekcygwDWYEWDNLPE 124

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 1043698614 133 VAIRRDDSILLAQHTRHRNGIHTVL-AGFVEVGETLEQAVAREVMEESGIKVKNLRY--VTSQ-------PWPFPMSLMT 202
Cdd:cd04679     7 AAILDDGRLLLVLRLRAPEAGHWGLpGGKVDWLETVEDAVRREILEELGLEIELTRLlcVVDQidaadgeHWVAPVYLAE 86

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1043698614 203 AFmaeydSGEIVIDQKE-LLEANWYRYDDLP 232
Cdd:cd04679    87 IF-----SGEPRLMEPEkHGGIGWFALDALP 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614 127 IAPCIIVAirrDDSILLAQhtRH---RNGIHTVLAGFVEVGETLEQAVAREVMEESGIKV 183
Cdd:cd04511     4 VVGCLPEW---EGKVLLCR--RAiepRKGYWTLPAGFMELGETTEQGAARETREEAGARV 58

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 1043698614 134 AIRRDDSILLaqhTRHR-NGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVT------SQPWPFPMSLMTAFM- 205
Cdd:cd04672     8 AVFKDGKILL---VREKsDGRWTLPGGWADVGLSPAENAVKEVREESGYEVRARKLLAvfdrnkGGHPPSPFHVYKLFFl 84

                          90       100
                  ....*....|....*....|....*....
gi 1043698614 206 AEYDSGEiVIDQKELLEANWYRYDDLPLL 234
Cdd:cd04672    85 CELIGGE-AQTSIETSEVGFFALDDLPPL 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 1043698614 133 VAIRRDDSILLAqhtRHRNGIHTVLA-GFVEVGETLEQAVAREVMEESGIKVKN--LRYVTS-------QPwPFPMsLMT 202
Cdd:cd04690     6 VIIIKDGRLLLV---RKRGTDAFYLPgGKREPGETPLQALVRELKEELGLDLDPdsLRFLGTfeapaanEP-GTTV-RMT 80

                          90       100
                  ....*....|....*....|....*...
gi 1043698614 203 AFMAEYDsGEIVIDQkELLEANWYRYDD 230
Cdd:cd04690    81 CFTADYD-GEPQPAA-EIEELRWLDPAD 106

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 1043698614 159 GFVEVGETLEQAVAREVMEESGIKVKNLRYvtsqpwPFPMSLM-----------TAFMAEYDSGEIVIDQKELLEANWYR 227
Cdd:cd03428    35 GHVEPGESELETALRETKEETGLTVDDLPP------GFRETLTysfkegvektvVYFLAELTPDVEVKLSEEHQDYKWLP 108

                  ...
gi 1043698614 228 YDD 230
Cdd:cd03428   109 YEE 111

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 1043698614 133 VAIRRDDSILLAQHTRHR-NGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKnLRYVTSQPWPFPMSLMTAFMAEYDSG 211
Cdd:cd04671     6 VIINEQGEVLMIQEAKRScRGKWYLPAGRVEPGESIVEAAKREVKEETGLKCE-PSTLLSVEEAGGSWYRFVFTGNITGG 84

                          90       100
                  ....*....|....*....|.
gi 1043698614 212 EI-VIDQKELLEANWYRYDDL 231
Cdd:cd04671    85 KLkTPADADSESLQAFWIDDI 105

GDP-mannose hydrolase (GDPMK), and similar proteins; GDP-mannose hydrolase (GDPMK) is a NUDIX enzyme that uses GDP-mannose as the preferred substrate. It is distinct from Nudix ADP-ribose hydrolases. GDPMK and ADP-ribose pyrophosphatase seem to use similar catalytic mechanism. However, GDPMK hydrolysis does not rely on a single glutamate as the catalytic base; rather, it is dependent on residues that coordinate the magnesium ions and residues that position the substrate properly for catalysis. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1043698614 156 VLAGFVEvGETLEQAVAREVMEESGIKVKNLRYVtSQPWPFP---MSLMTAFMAEYDS 210
Cdd:cd24157    41 ACAGLLD-GDDPEDCIRREAEEETGYRLGDLEKV-FTAYSSPgivTERIHLFIAEYSS 96

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1043698614 158 AGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPMS----LMTAFMAEYDS--GEIVIDQkELLEANWYRYDDL 231
Cdd:cd03675    30 AGHLEPGESLLEAAIRETLEETGWEVEPTALLGIYQWTAPDNgvtyLRFAFAGELLEhlPDQPLDS-GIIRAHWLTLEEI 108

NUDIX domain family found in Deinococcus radiodurans, and similar proteins; Deinococcus radiodurans protein DR_0079 is one of 21 NUDIX hydrolases that it encodes, and it has been observed to have a marked preference for cytosine ribonucleoside 5'-diphosphate (CDP) and cytosine ribonucleoside 5'-triphosphate (CTP), and for their corresponding deoxyribose nucleotides, dCDP and dCTP, to a lesser degree. 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 1043698614 158 AGFVEVGETLEQAVAREVMEESGIKVKNLRY-VTSQPWPFPMSLmTAFMAEYdsgEIVIDQ 217
Cdd:cd24154    37 GGHVSSGETYEQAFVRELQEELNLDLDQLSYrVLGKLTPYEHGV-SAFMKVY---EIRSDE 93

diadenosine hexaphosphate (Ap6A) hydrolase; Diadenosine hexaphosphate (Ap6A) hydrolase is a member of the NUDIX hydrolase superfamily. Ap6A hydrolase specifically hydrolyzes diadenosine polyphosphates, but not ATP or diadenosine triphosphate, and it generates ATP as the product. Ap6A, the most preferred substrate, hydrolyzes to produce two ATP molecules, which is a novel hydrolysis mode for Ap6A. These results indicate that Ap6A hydrolase is a diadenosine polyphosphate hydrolase. It requires the presence of a divalent cation, such as Mn2+, Mg2+, Zn2+, and Co2+, for activity. Members of the NUDIX hydrolase superfamily are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1043698614 161 VEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPMSLMTA------FMAEYDSGEIVIDQK-ELLEANWYRYDDL 231
Cdd:cd03673    36 LEPGETPEEAAVREVEEETGLRVRLGRPLGTTRYTYTRKGKGIlkkvhyWLMRALGGEFLPQPEeEIDEVRWLPPDEA 113

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1043698614 150 RNGI---HTVLA---GFVEVGETLEQAVAREVMEESGIKV 183
Cdd:cd04674    21 RRGIepgHGELAlpgGYIEYGETWQEAAVRELREETGVEA 60