NCBI Conserved Domain Search

NAD(+) diphosphatase;

Pssm-ID: 234699 [Multi-domain] Cd Length: 256 Bit Score: 490.52 E-value: 1.82e-178

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886   1 MDRIIEKSDLGWWIVSHEQKLWLPGGELPYGAAETFDLVGQPALKIGEWQGEPVWLIQQS--RRQDMGSVRQVLDLDVGL 78
Cdd:PRK00241   3 MRRDLEALDAGWWVVSHEQQLWLPDGELPFGAAANLDLPGLRALQIGEWQGEPVWLVRQDplRGHEMGSLRQLLDLDDGL 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886  79 FQLAGRGVQLAEFYRSHKYCGYCGHTMHPSKTEWAMLCSHCRERYYPQIAPCIIVAIRRDDSILLAQHTRHRNGIHTVLA 158
Cdd:PRK00241  83 FQLLGRAVQLAEFYRSHRFCGYCGHPMHPSKTEWAMLCPHCRERYYPRIAPCIIVAVRRGDEILLARHPRHRNGVYTVLA 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 159 GFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPQSLMTAFMADYDSGEIVIDQKELLDANWYRYDDLPLLPPPG 238
Cdd:PRK00241 163 GFVEVGETLEQCVAREVMEESGIKVKNLRYVGSQPWPFPHSLMLGFHADYDSGEIVFDPKEIADAQWFRYDELPLLPPSG 242

                        250
                 ....*....|....
gi 495778886 239 TVARRLIEDTVAMC 252
Cdd:PRK00241 243 TIARRLIEDTVALC 256

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

Pssm-ID: 442065 [Multi-domain] Cd Length: 288 Bit Score: 326.49 E-value: 3.44e-113

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886  11 GWWIVSHEQKLWLPGGE----LPYGAAETFDlVGQPALKIGEWQGEPVWLIQQSR------RQDMGSVRQVLD-LDVGLF 79
Cdd:COG2816   31 PRVLVVDGGRLLLLEDGgellLPAGEAADLG-PPAEAVFLGLDDGRPVFAVDLPAelelpeGAEFVDLRELGGlLDPRDA 109

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886  80 QLAGRGVQLAEFYRSHKYCGYCGHTMHPSKTEWAMLCSHCRERYYPQIAPCIIVAIRRDDSILLAQHTRHRNGIHTVLAG 159
Cdd:COG2816  110 GLAARAVALLNWHRTHRFCGRCGAPTVVAAAGWARRCPACGAEHYPRTDPAVIVLVTDGDRILLARQARWPPGRYSLLAG 189

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 160 FVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPQSLMTAFMADYDSGEIVIDQKELLDANWYRYDDLP------L 233
Cdd:COG2816  190 FVEPGETLEQAVRREVFEEVGVRVKNVRYVGSQPWPFPSSLMLGFTAEADSGEITVDGDEIEDARWFSRDELPaalaglL 269

                        250
                 ....*....|....*....
gi 495778886 234 LPPPGTVARRLIEDTVAMC 252
Cdd:COG2816  270 LPPPGSIARRLIEAWLAGP 288

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

Pssm-ID: 467535 [Multi-domain] Cd Length: 126 Bit Score: 195.79 E-value: 6.19e-64

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 128 APCIIVAIRRD-DSILLAQHTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPQSLMTAFMA 206
Cdd:cd03429    1 DPAVIVLVTNGeDKILLARQPRWPPGRYSLLAGFVEPGETLEEAVRREVKEEVGLRVKNVRYVGSQPWPFPSSLMLGFTA 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 495778886 207 DYDSGEIVIDQKELLDANWYRYDDLP---LLPPPGTVARRLIED 247
Cdd:cd03429   81 EADSGEITVDDDELEDARWFSRDELPealFLPPPGSIARRLIRA 124

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 81.95 E-value: 1.04e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 130 CIIVaiRRDDSILLAQHTR-HRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFP-QSLMTAFMAD 207
Cdd:COG1051   11 AVIF--RKDGRVLLVRRADePGKGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHPDRgHVVSVAFLAE 88

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 495778886 208 YDSGEIVIDQkELLDANWYRYDDLPLLPPPGTVARRL 244
Cdd:COG1051   89 VLSGEPRADD-EIDEARWFPLDELPELAFTPADHEIL 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.

Pssm-ID: 467573 [Multi-domain] Cd Length: 122 Bit Score: 71.56 E-value: 8.53e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 137 RDDSILLAQHTRHRN-GIHTVLAGFVEVGETLEQAVAREVMEESGI--KVKNLRYVTSQPWPFPQS-LMTAFMADYDSGE 212
Cdd:cd04691   10 KEGKVLLVKRAYGPGkGRWTLPGGFVEEGETLDEAIVREVLEETGIdaKPVGIIGVRSGVIRDGKSdNYVVFLLEYVGGE 89

                         90
                 ....*....|....*....
gi 495778886 213 IVIDQKELLDANWYRYDDL 231
Cdd:cd04691   90 PKPDERENSEAGFLTLEEA 108

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 71.36 E-value: 1.40e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886  131 IIVAIRRDDSILLAQHT-RHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFP-------QSLMT 202
Cdd:pfam00293   7 GVVLLNEKGRVLLVRRSkKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPfdgrfpdEHEIL 86

                          90       100       110
                  ....*....|....*....|....*....|....
gi 495778886  203 AFMADYDSGEIVIDQ-KELLDANWYRYDDLPLLP 235
Cdd:pfam00293  87 YVFLAEVEGELEPDPdGEVEEVRWVPLEELLLLK 120

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

Pssm-ID: 467528 [Multi-domain] Cd Length: 106 Bit Score: 67.82 E-value: 1.31e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 130 CIIVAIRRDDSILLAQHTRHRNGIH-TVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFP----QSLMTAF 204
Cdd:cd02883    3 VGAVVFDDEGRVLLVRRSDGPGPGGwELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPdegrHVVVLVF 82

                         90       100
                 ....*....|....*....|..
gi 495778886 205 MADYDSGEIVIDQK-ELLDANW 225
Cdd:cd02883   83 LARVVGGEPPPLDDeEISEVRW 104

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

Pssm-ID: 467564 [Multi-domain] Cd Length: 135 Bit Score: 66.05 E-value: 1.21e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 123 YYPQIAPCIIVAIRRDDSILLAqhTRHRN---GIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPQS 199
Cdd:cd04681    1 YFHNVAAAVGVIIRNEGEILFV--RRAKEpgkGKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYLCSLPNTYLYK 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 495778886 200 LMTA------FMADYDS-GEIVIDQKELLDANWYRYDDLPLLP 235
Cdd:cd04681   79 GITYktcdlfFTAELDEkPKLKKAEDEVAELEWLDLEEIEPEK 121

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

Pssm-ID: 467590 [Multi-domain] Cd Length: 142 Bit Score: 66.07 E-value: 1.22e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 130 CIIVAIRRDDSILLAQhtRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYV---TSQPWPFP-----QSLM 201
Cdd:cd18879   21 VTAVVLRDAGRVLLVR--RADNGRWTPVTGIVEPGEQPADAAVREVLEETGVDVEVERLAsvgASPPVTYPngdqcQYLD 98

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 495778886 202 TAFMADYDSGEIVIDQKELLDANWYRYDDlplLPPPGTVARRLIED 247
Cdd:cd18879   99 LTFRCRPVGGEARVNDDESLEVGWFPVDA---LPPMLPRFRRRIAL 141

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

Pssm-ID: 467560 [Multi-domain] Cd Length: 137 Bit Score: 62.92 E-value: 1.64e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 125 PQIAPCIIVAIRRDDSILLAQHtRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLR----------YVTsqpw 194
Cdd:cd04677    9 PLILVGAAVIILNEQGRILLQK-RTDTGDWGLPGGAMELGESLEETARREVFEETGLTVEELEllgvysgkdlYYT---- 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 495778886 195 pFP-----QSLMTAFMADYDSGEIVIDQKELLDANWYRYDDLP-LLPPPgtvARRLIE 246
Cdd:cd04677   84 -YPngdevYNVTAVYLVRDVSGELKVDDEESLELRFFSLDELPeNINPQ---HRDVIE 137

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

Pssm-ID: 440260 [Multi-domain] Cd Length: 143 Bit Score: 62.36 E-value: 3.48e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 131 IIVAIRRDDSILLAQHTRHRNGIHTVL--AGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWP-FPQSLMTAFMAD 207
Cdd:COG0494   17 VVVLLDDDGRVLLVRRYRYGVGPGLWEfpGGKIEPGESPEEAALRELREETGLTAEDLELLGELPSPgYTDEKVHVFLAR 96

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 495778886 208 Y---DSGEIVIDQKELLDANWYRYDDLPLLPPPGTVARRLIE 246
Cdd:COG0494   97 GlgpGEEVGLDDEDEFIEVRWVPLDEALALVTAGEIAKTLAA 138

MutT pyrophosphohydrolase; The MutT pyrophosphohydrolase is a prototypical NUDIX hydrolase that catalyzes the hydrolysis of nucleoside and deoxynucleoside triphosphates (NTPs and dNTPs) by substitution at a beta-phosphorus to yield a nucleotide monophosphate (NMP) and inorganic pyrophosphate (PPi). This enzyme requires two divalent cations for activity; one coordinates the phosphoryl groups of the NTP/dNTP substrate, and the other coordinates to the enzyme. It also contains the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as metal binding and catalytic site. MutT pyrophosphohydrolase is important in preventing errors in DNA replication by hydrolyzing mutagenic nucleotides such as 8-oxo-dGTP (a product of oxidative damage), which can mispair with template adenine during DNA replication, to guanine nucleotides.

Pssm-ID: 467531 [Multi-domain] Cd Length: 123 Bit Score: 60.54 E-value: 8.61e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 131 IIVA---IRRDDSILLAQhtRHRNGihtVLAGF-------VEVGETLEQAVAREVMEESGIKVKNLRYVT--SQPWPFPQ 198
Cdd:cd03425    1 IEVVaaiIVDDGRVLIAQ--RPEGK---HLAGLwefpggkVEPGETPEQALVRELREELGIEVEVGEPLGtvEHDYPDFH 75

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 495778886 199 SLMTAFMADYDSGEIVidQKELLDANWYRYDDLPLLP 235
Cdd:cd03425   76 VRLHVYLCTLWSGEPQ--LLEHQELRWVTPEELDDLD 110

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

Pssm-ID: 467586 [Multi-domain] Cd Length: 125 Bit Score: 59.61 E-value: 2.13e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 129 PCIIVAIRRDDSILLAQHTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPQS-------LM 201
Cdd:cd18874    3 PTVGALIFNPDGKVLLVRSHKWNDLYGIPGGKVEWGETLEEALKREVKEETGLDITDIRFILVQESINSEEfhkpahfVF 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 495778886 202 TAFMADYDSGEIVIDQ-------KELLDAnwyryDDLPLlpppGTVARRLIE 246
Cdd:cd18874   83 VDYLARTDSSEVVLNEeaveylwVEPEEA-----LKYPL----NSFTRLLLE 125

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

Pssm-ID: 467596 [Multi-domain] Cd Length: 147 Bit Score: 58.01 E-value: 1.45e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 135 IRRDDSILLAQHTRHRN-GIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRY--VTSQPWPFPQS--LMTAFMADYD 209
Cdd:cd18886    7 IIRDDEVLLLNRNKKPNmGKWNGVGGKLEPGESPEECAIREVFEETGLELEDLQLrgIVTFPSFDGGEdwLMYVFLAEAF 86

                         90       100
                 ....*....|....*....|....*..
gi 495778886 210 SGEIVIDQKE-LLDanWYRYDDLPLLP 235
Cdd:cd18886   87 SGELVESDREgILA--WVPIDWLLNLP 111

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

Pssm-ID: 467557 [Multi-domain] Cd Length: 128 Bit Score: 57.52 E-value: 1.48e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 131 IIVAIRRDDSILLAQhtRHRN---GIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPQS-------- 199
Cdd:cd04673    4 VGAVVFRDGRVLLVR--RGNPpdaGLWSFPGGKVELGETLEDAALRELREETGLEAEVVGLLTVVDVIERDEagrvrfhy 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 495778886 200 LMTAFMADYDSGEIVIDQkELLDANWYRYDDLPLLP-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.

Pssm-ID: 467530 [Multi-domain] Cd Length: 134 Bit Score: 55.98 E-value: 4.81e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 495778886 130 CIIVAIRRDDSILLAQHTRHrnGIHTVL----AGFVEVGETLEQAVAREVMEESGIKVKNLRYVTS 191
Cdd:cd03424    5 VAVLAITDDGKVVLVRQYRH--PVGRVLlelpAGKIDPGEDPEEAARRELEEETGYTAGDLELLGS 68

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

Pssm-ID: 467599 [Multi-domain] Cd Length: 127 Bit Score: 56.08 E-value: 5.12e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 134 AIRRDDSILLAQHtrhRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPW------PFPQSLMTAF-MA 206
Cdd:cd18889    8 AIFKDDKILLVQE---KDGRWSLPGGWVDVNQSIKENTIKEAKEEAGLDVEPKRIIAVLDRnkhnkpPYAYGIYKIFvLC 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 495778886 207 DYDSGEIViDQKELLDANWYRYDDLPLLPPPGTVARRliedtVAMC 252
Cdd:cd18889   85 ELLGGEFQ-PNIETIESGYFSLDELPPLSEEKNTKEQ-----IEMC 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.

Pssm-ID: 467591 [Multi-domain] Cd Length: 126 Bit Score: 54.84 E-value: 1.09e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 495778886 135 IRRDDSILLAQHtRHRNGIHTVL-AGFVEVGETLEQAVAREVMEESGIKVK 184
Cdd:cd18880    8 IIEDGKLLLVKH-RDEGGIFYILpGGGQEHGETLPEALKRECLEETGLDVE 57

NADH pyrophosphatase zinc ribbon domain; This domain is found in between two duplicated NUDIX domains. It has a zinc ribbon structure.

Pssm-ID: 430510 [Multi-domain] Cd Length: 32 Bit Score: 52.21 E-value: 1.44e-09

                          10        20        30
                  ....*....|....*....|....*....|..
gi 495778886   93 RSHKYCGYCGHTMHPSKTEWAMLCSHCRERYY 124
Cdd:pfam09297   1 RTHRFCGRCGAPTVPAEGGWARVCPSCGHEHY 32

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

Pssm-ID: 467552 [Multi-domain] Cd Length: 117 Bit Score: 53.44 E-value: 3.35e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 133 VAIRRDDSILLaqhTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQpwPFPQSLMTAFMADYDSGE 212
Cdd:cd04667    5 VICRRGDRILL---VARRGGRWLLPGGKIEPGESPLEAAIRELKEETGLAALSLLYLFEH--EGPHKLHHVFLAEAPDGG 79

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 495778886 213 IVIDQKELLDANWYRYDDLPLLPPPGTvARRLIED 247
Cdd:cd04667   80 RPRPGNEIARCRWVSADQLRDLNLSRA-TRLIVRR 113

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

Pssm-ID: 467561 [Multi-domain] Cd Length: 128 Bit Score: 53.34 E-value: 4.07e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 130 CIIVaiRRDDSILLAQHT-RHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVT---SQPWPFPQSLMTAFM 205
Cdd:cd04678    7 VIVL--NDDGKVLLGRRKgSHGAGTWALPGGHLEFGESFEECAAREVLEETGLEIRNVRFLTvtnDVFEEEGKHYVTIFV 84

                         90       100       110
                 ....*....|....*....|....*....|....
gi 495778886 206 -ADYDSGE--IVIDQKELLDANWYRYDDLPLLPP 236
Cdd:cd04678   85 lAEVDDGEpeENMEPDKCEGWEWFSWDELPPLRP 118

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

Pssm-ID: 467554 [Multi-domain] Cd Length: 131 Bit Score: 53.31 E-value: 5.42e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 159 GFVEVGETLEQAVAREVMEESGIKVK-----NLRyvTSQPWPFPQS------LMTAfmadYDSGEIVIDQKELLDANWYR 227
Cdd:cd04670   34 GLVDPGEDIGEAAVREVFEETGIDTEfvsilGFR--HQHPGRFGKSdlyfvcRLRP----LSDEEIKICPEEIAEAKWMP 107


                 ....
gi 495778886 228 YDDL 231
Cdd:cd04670  108 LEEY 111

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

Pssm-ID: 467563 [Multi-domain] Cd Length: 121 Bit Score: 52.64 E-value: 6.86e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 133 VAIRRDDSILLAQHTrHRNGIHtVLAGFVEVGETLEQAVAREVMEESGIKVKN---LRYVTSQPWPFPQSLMTAFMAD-Y 208
Cdd:cd04680    6 IVLDDAGRVLLVRHT-YVPGWY-LPGGGVDKGETAEEAARRELREEAGVVLTGpprLFGVYFNRRVSPRDHVALYRVReF 83

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 495778886 209 DSGEIVIDQKELLDANWYRYDDLPLLPPPGTvARRLIE 246
Cdd:cd04680   84 EQTEPPEPNGEIAEAGFFALDALPEDTTPAT-RRRLAE 120

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

Pssm-ID: 467570 [Multi-domain] Cd Length: 130 Bit Score: 52.55 E-value: 7.62e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 495778886 135 IRRDDSILLAQHtrHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYV 189
Cdd:cd04688    9 IIRDGKVLLARG--EDDDYYRLPGGRVEFGETSEDALVREFKEELGVEVEVVRLL 61

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

Pssm-ID: 182536 [Multi-domain] Cd Length: 135 Bit Score: 52.05 E-value: 1.45e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 132 IVA--IRRDDSILLAQHTRHRN--GIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPQSL--MTAFM 205
Cdd:PRK10546   6 VVAaiIERDGKILLAQRPAHSDqaGLWEFAGGKVEPGESQPQALIRELREELGIEATVGEYVASHQREVSGRRihLHAWH 85

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 495778886 206 ADYDSGEIVIDQKELLdaNW------YRYD----DLPLL 234
Cdd:PRK10546  86 VPDFHGELQAHEHQAL--VWctpeeaLRYPlapaDIPLL 122

nudix hydrolase

Pssm-ID: 215184 [Multi-domain] Cd Length: 144 Bit Score: 52.17 E-value: 1.63e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 125 PQIApcIIVAIRRDDSILLAQHtRHRNGIHT--VLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVT-------SQPWP 195
Cdd:PLN02325   8 PRVA--VVVFLLKGNSVLLGRR-RSSIGDSTfaLPGGHLEFGESFEECAAREVKEETGLEIEKIELLTvtnnvflEEPKP 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 495778886 196 --FPQSLMTAFMADYDSGEIVIDQKELLDANWYRYDDLPL 233
Cdd:PLN02325  85 shYVTVFMRAVLADPSQVPQNLEPEKCYGWDWYEWDNLPE 124

RNA pyrophosphohydrolase; The initiation of mRNA degradation often requires deprotection of its 5' end. In eukaryotes, the 5'-methylguanosine (cap) structure is principally removed by the NUDIX family decapping enzyme Dcp2, yielding a 5'-monophosphorylated RNA that is a substrate for 5' exoribonucleases. In bacteria, the 5'-triphosphate group of primary transcripts is also converted to a 5' monophosphate by a NUDIX protein called RNA pyrophosphohydrolase (RppH), allowing access to both endo- and 5' exoribonucleases. NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

Pssm-ID: 467550 [Multi-domain] Cd Length: 121 Bit Score: 50.33 E-value: 4.36e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 131 IIVAIRRDDSILLAQHtRHRNGIHTVlAGFVEVGETLEQAVAREVMEESGIKVKNLRY-----VTSQPWPFPQSLMTA-- 203
Cdd:cd04665    3 VVVIARYKGKWLFTRH-KERRGWEFP-GGKREPGETIEEAARRELYEETGAVIFELKPlgqysVHGKGQEFFGAVYYAev 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 495778886 204 --FMADYDSGEI--VIDQKELLDANWYRYDDLPLL 234
Cdd:cd04665   81 ksFEPILPYFETaeVRLFDELPEFSLTYPDIQPHL 115

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

Pssm-ID: 467545 [Multi-domain] Cd Length: 123 Bit Score: 47.96 E-value: 3.09e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 127 IAPCIIVAirrDDSILLAQhtRH---RNGIHTVLAGFVEVGETLEQAVAREVMEESGIKV 183
Cdd:cd04511    4 VVGCLPEW---EGKVLLCR--RAiepRKGYWTLPAGFMELGETTEQGAARETREEAGARV 58

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

Pssm-ID: 467562 [Multi-domain] Cd Length: 126 Bit Score: 47.69 E-value: 3.90e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 133 VAIRRDDSILLAQHTRHRNGIHTVL-AGFVEVGETLEQAVAREVMEESGIKVKNLRY--VTSQ-------PWPFPQSLMT 202
Cdd:cd04679    7 AAILDDGRLLLVLRLRAPEAGHWGLpGGKVDWLETVEDAVRREILEELGLEIELTRLlcVVDQidaadgeHWVAPVYLAE 86

                         90       100       110
                 ....*....|....*....|....*....|.
gi 495778886 203 AFmadydSGEIVIDQKE-LLDANWYRYDDLP 232
Cdd:cd04679   87 IF-----SGEPRLMEPEkHGGIGWFALDALP 112

MutT homolog-1 (MTH1); MutT homolog-1 (MTH1; EC 3.6.1.- ), also called nucleoside diphosphate-linked moiety X)) motif 1 (Nudt1), is a member of the NUDIX hydrolase superfamily. MTH1, the mammalian counterpart of MutT, hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-ATP, to monophosphates, thereby preventing the incorporation of such oxygen radicals during replication. This is an important step in the repair mechanism in genomic and mitochondrial DNA. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity, and contain the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. MTH1 is predominantly localized in the cytoplasm and mitochondria. Structurally, this enzyme adopts a similar fold to MutT despite low sequence similarity outside the conserved NUDIX motif. The most distinctive structural difference between MutT and MTH1 is the presence of a beta-hairpin, which is absent in MutT. This results in a much deeper and narrower substrate binding pocket. Mechanistically, MTH1 contains dual specificity for nucleotides that contain 2-OH-adenine bases and those that contain 8-oxo-guanine bases.

Pssm-ID: 467533 [Multi-domain] Cd Length: 136 Bit Score: 47.91 E-value: 3.91e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 135 IRRDDSILLAQHTR-----HRNGIhtvlAGFVEVGETLEQAVAREVMEESGIKVKNLRYV-------TSQPWPFPqslMT 202
Cdd:cd03427    9 LRGDDRVLLGLKKRgfgagKWNGF----GGKVEPGETIEEAAVRELEEEAGLTATELEKVgrlkfefPDDPEAMD---VH 81

                         90       100       110
                 ....*....|....*....|....*....|.
gi 495778886 203 AFMADYDSGEIVidQKELLDANWYRYDDLPL 233
Cdd:cd03427   82 VFRADSWTGEPQ--ETEEMRPQWFDLDDIPY 110

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

Pssm-ID: 467588 [Multi-domain] Cd Length: 121 Bit Score: 46.81 E-value: 8.63e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 159 GFVEVGETLEQAVAREVMEESGIKVKNLR-----YVTSQPWPFPQSLMTafmadYDSGE--------IVIDQKELLDANW 225
Cdd:cd18876   30 GVVEAGESPLQAARREVREELGLDVPVGRllavdWVPPAGGGDDAVLFV-----FDGGVltpeqaaaIRLQDEELSAYRF 104

                         90
                 ....*....|....*....
gi 495778886 226 YRYDDLP-LLPPPgtVARR 243
Cdd:cd18876  105 VTPEEAAeLLPPR--LARR 121

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

Pssm-ID: 467566 [Multi-domain] Cd Length: 137 Bit Score: 46.44 E-value: 1.29e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 133 VAIRRDDSILLAQ--HTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVK--NLRYVT---SQPWPFPQSLMTAFM 205
Cdd:cd04683    5 LLLVRGDEVLLLRraNTGYDDGWWHLPAGHVEAGETVRAAAVREAKEELGVEIDpeDLRLVHtmhRRSDGGRERIDFFFR 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 495778886 206 ADYDSGEIVIDQKE-LLDANWYRYDDLPllpppgtvarrliEDTVAMCRA 254
Cdd:cd04683   85 ATRWSGEPRNREPDkCAELRWFPLDALP-------------ENTVPYVRA 121

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

Pssm-ID: 467587 [Multi-domain] Cd Length: 144 Bit Score: 46.79 E-value: 1.45e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 130 CIIvaIRRDDSILLAQHTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPQS---LMTAFMA 206
Cdd:cd18875    7 CMI--YDGEDRVLVLDRVKKDWGGYTFPGGHVEPGESFVDSVIREVKEETGLTIKNPELCGIKQWINPDGeryIVFLYKT 84

                         90       100
                 ....*....|....*....|....*..
gi 495778886 207 DYDSGEIV---------IDQKELLDAN 224
Cdd:cd18875   85 DHFSGELLsseegelfwIPIEELKKLP 111

CDP-Choline Pyrophosphatase and similar proteins; Members include: CDP-Choline Pyrophosphatase, ADP-ribose pyrophosphatase, and UDP-X diphosphatase. CDP-choline pyrophosphatase catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. ADP-ribose pyrophosphatase catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. UDP-X diphosphatase hydrolyzes UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-alanine. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467556 [Multi-domain] Cd Length: 128 Bit Score: 45.63 E-value: 2.83e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 134 AIRRDDSILLaqhTRHR-NGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVT------SQPWPFPQSLMTAFM- 205
Cdd:cd04672    8 AVFKDGKILL---VREKsDGRWTLPGGWADVGLSPAENAVKEVREESGYEVRARKLLAvfdrnkGGHPPSPFHVYKLFFl 84

                         90       100
                 ....*....|....*....|....*....
gi 495778886 206 ADYDSGEiVIDQKELLDANWYRYDDLPLL 234
Cdd:cd04672   85 CELIGGE-AQTSIETSEVGFFALDDLPPL 112

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 46.41 E-value: 5.56e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 495778886 133 VAIRRDDSILLAQHTRHRngihtVLAGF-------VEVGETLEQAVAREVMEESGIKVKNLRyvtsqPW 194
Cdd:PRK08999  11 VIRDADGRILLARRPEGK-----HQGGLwefpggkVEPGETVEQALARELQEELGIEVTAAR-----PL 69

UDP-X diphosphatase; UDP-X diphosphatase hydrolyzes UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-alanine, the last step of the Mur pathway of peptidoglycan biosynthesis. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467601 [Multi-domain] Cd Length: 128 Bit Score: 44.31 E-value: 7.94e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 135 IRRDDSILLAQHTRHrnGIHTVLAGFVEVGETLEQAVAREVMEESGIKV--KNLR--YVTSQPWPFPQSLM---TAFMAD 207
Cdd:cd18891    9 IQNENKVLLVQDKHT--KEWALPGGFAEVGLSPKENILKEVKEETGLHVevERLLavFDTDLRQDIPQSFQyykFIFACK 86

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 495778886 208 YDSGEIViDQKELLDANWYRYDDLPLLPPPGTVARRL 244
Cdd:cd18891   87 ILDGEFQ-ENSETSDLQYFSLDQLPNLSLKRTTKEQL 122

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

Pssm-ID: 467603 [Multi-domain] Cd Length: 187 Bit Score: 44.82 E-value: 9.65e-06

                         10        20        30
                 ....*....|....*....|....*....|....
gi 495778886 158 AGFVEVGETLEQAVAREVMEESGIKVKNLRYVTS 191
Cdd:cd24155   82 AGMIDAGETPEDVARREAEEEAGLTLDALEPIAS 115

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

Pssm-ID: 467542 [Multi-domain] Cd Length: 130 Bit Score: 43.79 E-value: 1.06e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 159 GFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPW-----PFPQSLMTA--------FMADYDSGEIVIDQKELLDANW 225
Cdd:cd03674   32 GHVEPDEDPLEAALREAREETGLDVELLSPLSPDPLdidvhPIPANPGEPahlhldvrYLAVADGDEALRKSDESSDVRW 111

                         90
                 ....*....|....*....
gi 495778886 226 YRYDDLPLLPPPGTVARRL 244
Cdd:cd03674  112 FPLDELEELSMDPNLRKLL 130

8-oxo-DGDP phosphatase; 8-oxo-DGDP phosphatase (8DGDPP; EC 3.6.1.55), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 18/Nudt18; 2-hydroxy-DADP phosphatase; 7,8-dihydro-8-oxoguanine phosphatase, hydrolyzes 8-oxo-7,8-dihydroguanine (8-oxo-Gua)-containing deoxyribo- and ribonucleoside diphosphates to the monophosphates. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467555 [Multi-domain] Cd Length: 130 Bit Score: 43.84 E-value: 1.11e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 133 VAIRRDDSILLAQHTRHR-NGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKnLRYVTSQPWPFPQSLMTAFMADYDSG 211
Cdd:cd04671    6 VIINEQGEVLMIQEAKRScRGKWYLPAGRVEPGESIVEAAKREVKEETGLKCE-PSTLLSVEEAGGSWYRFVFTGNITGG 84

                         90       100
                 ....*....|....*....|.
gi 495778886 212 EI-VIDQKELLDANWYRYDDL 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.

Pssm-ID: 467605 Cd Length: 146 Bit Score: 43.32 E-value: 2.46e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 495778886 156 VLAGFVEvGETLEQAVAREVMEESGIKVKNLRYVtSQPWPFPQSL---MTAFMADYDS 210
Cdd:cd24157   41 ACAGLLD-GDDPEDCIRREAEEETGYRLGDLEKV-FTAYSSPGIVterIHLFIAEYSS 96

diadenosine tetraphosphate; Diadenosine tetraphosphate (Ap4A; EC 3.6.1.17), also called NUDIX (nucleoside diphosphate-linked moiety X)) motif 2/Nudt2, is a member of the NUDIX hydrolase superfamily. Ap4A hydrolases are well represented in a variety of prokaryotic and eukaryotic organisms. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one subfamily and fungi/animals/archaea enzymes, represented by this subfamily, fall into another. Bacterial enzymes are found in both subfamilies. Ap4A is a potential by-product of aminoacyl tRNA synthesis, and accumulation of Ap4A has been implicated in a range of biological events, such as DNA replication, cellular differentiation, heat shock, metabolic stress, and apoptosis. Ap4A hydrolase cleaves Ap4A asymmetrically into ATP and AMP. It is important in the invasive properties of bacteria and thus presents a potential target for inhibition of such invasive bacteria. Besides the signature NUDIX motif (G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val) that functions as a metal binding and catalytic site, and a required divalent cation, Ap4A hydrolase is structurally similar to the other members of the NUDIX hydrolase superfamily with some degree of variation. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies.

Pssm-ID: 467534 [Multi-domain] Cd Length: 132 Bit Score: 42.54 E-value: 3.04e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 159 GFVEVGETLEQAVAREVMEESGIKVKNLRYvtsqpwPFPQSLM-----------TAFMADYDSGEIVIDQKELLDANWYR 227
Cdd:cd03428   35 GHVEPGESELETALRETKEETGLTVDDLPP------GFRETLTysfkegvektvVYFLAELTPDVEVKLSEEHQDYKWLP 108


                 ...
gi 495778886 228 YDD 230
Cdd:cd03428  109 YEE 111

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

Pssm-ID: 467548 [Multi-domain] Cd Length: 132 Bit Score: 42.28 E-value: 3.69e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 495778886 130 CIIVAIRRDDSILLAQHTRHRN-GIHtVLAGFVEVGETLEQAVAREVMEESGIK-VKNLRYVTSQPWPFPQ 198
Cdd:cd04663    4 CAYVTRGRNRELLVFEHPDFPEaGLQ-VPKGTVEPGESPEEAALRELAEETGLTgARVVVDLGSHDEGFEE 73

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

Pssm-ID: 467579 [Multi-domain] Cd Length: 118 Bit Score: 41.84 E-value: 3.84e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 495778886 135 IRRDDSILLAQHTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVK 184
Cdd:cd04699    9 IFDNGRVLLLRRSRAGAGEWELPGGRLEPGESPEEALKREVKEETGLDVS 58

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.

Pssm-ID: 467602 [Multi-domain] Cd Length: 121 Bit Score: 42.20 E-value: 3.88e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 495778886 158 AGFVEVGETLEQAVAREVMEESGIKVKNLRY-VTSQPWPFPQSLmTAFMADYdsgEIVIDQ 217
Cdd:cd24154   37 GGHVSSGETYEQAFVRELQEELNLDLDQLSYrVLGKLTPYEHGV-SAFMKVY---EIRSDE 93

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

Pssm-ID: 467572 [Multi-domain] Cd Length: 123 Bit Score: 41.75 E-value: 4.55e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 133 VAIRRDDSILLAqhtRHRNGIHTVLA-GFVEVGETLEQAVAREVMEESGIKVKN--LRYVTS-------QPwPFpQSLMT 202
Cdd:cd04690    6 VIIIKDGRLLLV---RKRGTDAFYLPgGKREPGETPLQALVRELKEELGLDLDPdsLRFLGTfeapaanEP-GT-TVRMT 80

                         90       100
                 ....*....|....*....|....*...
gi 495778886 203 AFMADYDsGEIVIDQkELLDANWYRYDD 230
Cdd:cd04690   81 CFTADYD-GEPQPAA-EIEELRWLDPAD 106

ADP-ribose pyrophosphatase NudF; Provisional

Pssm-ID: 182682 [Multi-domain] Cd Length: 202 Bit Score: 43.19 E-value: 4.79e-05

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 495778886 156 VLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTS 191
Cdd:PRK10729  86 MVAGMIEEGESVEDVARREAIEEAGLIVGRTKPVLS 121

8-oxo-dGTP diphosphatase MutT;

Pssm-ID: 182721 [Multi-domain] Cd Length: 129 Bit Score: 41.89 E-value: 5.59e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 495778886 159 GFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPQSLMT 202
Cdd:PRK10776  38 GKIEAGETPEQALIRELQEEVGITVQHATLFEKLEYEFPDRHIT 81

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

Pssm-ID: 467558 [Multi-domain] Cd Length: 118 Bit Score: 40.91 E-value: 9.22e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 495778886 150 RNGI---HTVLA---GFVEVGETLEQAVAREVMEESGIKV 183
Cdd:cd04674   21 RRGIepgHGELAlpgGYIEYGETWQEAAVRELREETGVEA 60

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

Pssm-ID: 467543 [Multi-domain] Cd Length: 138 Bit Score: 40.97 E-value: 1.20e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 158 AGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPQS----LMTAFMADYDS--GEIVIDQkELLDANWYRYDDL 231
Cdd:cd03675   30 AGHLEPGESLLEAAIRETLEETGWEVEPTALLGIYQWTAPDNgvtyLRFAFAGELLEhlPDQPLDS-GIIRAHWLTLEEI 108

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

Pssm-ID: 467595 [Multi-domain] Cd Length: 125 Bit Score: 40.86 E-value: 1.27e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 495778886 129 PCIIVAIRRDDSILLAQHTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGI 181
Cdd:cd18884   10 PVVAAIVEHDGHIVLARNKAWPEGWYGLVTGFLEAGESPEEAVLREVKEELGL 62

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

Pssm-ID: 467585 [Multi-domain] Cd Length: 132 Bit Score: 40.22 E-value: 2.29e-04

                         10        20
                 ....*....|....*....|....*....
gi 495778886 159 GFVEVGETLEQAVAREVMEESGIKVKNLR 187
Cdd:cd18873   38 GFVREDETLEDAARRELREETGLKDIYLE 66

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

Pssm-ID: 467578 [Multi-domain] Cd Length: 157 Bit Score: 40.30 E-value: 2.46e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 155 TVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQP--------WpfpqslMTAFMADYDsGEIVIDQKELLDANWY 226
Cdd:cd04697   58 PATGGVVGAGESYEENARRELEEELGIDGVPLRPLFTFYyeddrsrvW------GALFECVYD-GPLKLQPEEVAEVDWM 130


                 ....*
gi 495778886 227 RYDDL 231
Cdd:cd04697  131 SEDEI 135

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

Pssm-ID: 467569 [Multi-domain] Cd Length: 130 Bit Score: 39.58 E-value: 2.95e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 495778886 135 IRRDDSILLAQHTRhrnGIHTVL----AGFVEVGETLEQAVAREVMEESGIKV---KNLRYVTSQP 193
Cdd:cd04686    8 IIRNDKLLLIRKTR---GPYQGRydlpGGSQEFGESLEDALKREFAEETGMTVtsyDNLGVYDFFV 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.

Pssm-ID: 467559 [Multi-domain] Cd Length: 144 Bit Score: 39.69 E-value: 3.29e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 495778886 129 PCIIVAIRRDDSILLAQhtRHRNGIHTVL-AGFVEVGETLEQAVAREVMEESGIKVK 184
Cdd:cd04676   18 PSVAAVILNEDGRILLQ--RKGGLGLWSLpAGAIEPGEHPAEAVIREVREETGLLVK 72

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

Pssm-ID: 467541 [Multi-domain] Cd Length: 131 Bit Score: 39.07 E-value: 4.71e-04

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 495778886 161 VEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFP 197
Cdd:cd03673   36 LEPGETPEEAAVREVEEETGLRVRLGRPLGTTRYTYT 72

dihydroneopterin hydrolase; DHNTP pyrophosphatase (DHNTPase) catalyzes the hydrolysis of dihydroneopterin triphosphate (DHNTP) to dihydroneopterin monophosphate (DHNMP) and pyrophosphate,the second step in the pterin branch of the folate synthesis pathway in bacteria. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467549 [Multi-domain] Cd Length: 132 Bit Score: 38.77 E-value: 5.69e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 132 IVAIRRDDS--ILLAQHTrHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYV 189
Cdd:cd04664    5 VVIYRKDEEgeVLLLKRT-DDGGFWQSVTGGIEDGETPWQAALRELKEETGLDPLELQLI 63

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]

Pssm-ID: 129162 [Multi-domain] Cd Length: 185 Bit Score: 39.80 E-value: 6.41e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886  136 RRDDSILLAQ------HTRHRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTsQPWPFP---QSLMTAFMA 206
Cdd:TIGR00052  55 KKDTVVLIEQfriaayVNGEEPWLLELSAGMVEKGESPEDVARREAIEEAGYQVKNLRKLL-SFYMSPggvTELIHLFIA 133


                  ....
gi 495778886  207 DYDS 210
Cdd:TIGR00052 134 EVDD 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.

Pssm-ID: 467568 [Multi-domain] Cd Length: 138 Bit Score: 39.09 E-value: 6.43e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 495778886 132 IVAIRRDDSILLaQHTRHR-NGIHTVLA---GFVEVGETLEQAVAREVMEESGIKV 183
Cdd:cd04685    5 VLLLDPDGRVLL-FRFHDPdDPGRSWWFtpgGGVEPGESPEQAAVRELREETGLRL 59

plant diadenosine tetraphosphate (Ap4A) hydrolase and similar proteins; Diadenosine tetraphosphate (Ap4A) hydrolase is a member of the NUDIX hydrolase superfamily. Members of this family are well represented in a variety of prokaryotic and eukaryotic organisms. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one group (represented by this subfamily) and fungi/animals/archaea enzymes fall into another. Bacterial enzymes are found in both subfamilies. Ap4A is a potential by-product of aminoacyl tRNA synthesis, and accumulation of Ap4A has been implicated in a range of biological events, such as DNA replication, cellular differentiation, heat shock, metabolic stress, and apoptosis. Ap4A hydrolase cleaves Ap4A asymmetrically into ATP and AMP. It is important in the invasive properties of bacteria and thus presents a potential target for the inhibition of such invasive bacteria. Besides the signature NUDIX motif (G[X5]E[X7]REUXEEXGU where U is Ile, Leu, or Val), Ap4A hydrolase is structurally similar to the other members of the NUDIX hydrolase superfamily with some degree of variations. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies.

Pssm-ID: 467539 [Multi-domain] Cd Length: 147 Bit Score: 38.70 E-value: 7.66e-04

                         10        20        30
                 ....*....|....*....|....*....|.
gi 495778886 159 GFVEVGETLEQAVAREVMEESGIKVKNLRYV 189
Cdd:cd03671   34 GGIDEGEDPEEAALRELYEETGLSPEDVEII 64

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

Pssm-ID: 467567 [Multi-domain] Cd Length: 140 Bit Score: 38.37 E-value: 1.04e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 495778886 129 PCIIVAIRRDDS-ILLAQHTRHRngiHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYV 189
Cdd:cd04684   16 PGAYAVIFNDEGkVLLVQTPNGG---YFLPGGGIEPGETPEEALHREVLEETGWEIEIGEFL 74

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

Pssm-ID: 467593 [Multi-domain] Cd Length: 130 Bit Score: 38.01 E-value: 1.18e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 495778886 130 CIIVAIRRDDSILLaQHtRHRN-GIH-----TVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQPWPFPQ 198
Cdd:cd18882    4 AIAILYDDRGKVLL-QL-RDDKpGIPypgywGLFGGHLEPGETPEEAIRRELEEEIGYEPGEFRFFLLYTEDDGE 76

adenosine nucleotide hydrolase NudE; Provisional

Pssm-ID: 183303 Cd Length: 185 Bit Score: 37.86 E-value: 2.35e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 121 ERYYPQIAP-----CIIVAIRRDDSILLAQHtrHRNGIHTVLAGF----VEVGETLEQAVAREVMEESGI---KVKNLRY 188
Cdd:PRK11762  36 ERVYERMRPsgrgaVMIVPILDDDTLLLIRE--YAAGTERYELGFpkglIDPGETPLEAANRELKEEVGFgarQLTFLKE 113

                         90
                 ....*....|....*...
gi 495778886 189 VTSQPWPFpQSLMTAFMA 206
Cdd:PRK11762 114 LSLAPSYF-SSKMNIVLA 130

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

Pssm-ID: 467575 [Multi-domain] Cd Length: 157 Bit Score: 37.12 E-value: 3.39e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 135 IRRDDSILLAQhtRHRNGIH------TVLAGFVEVGETLEQAVAREVMEESGIKV--KNLRYVTSQpwPFPQSLMTAFMA 206
Cdd:cd04693   37 FNSDGEILIQQ--RSPDKKGfpgmweASTGGSVLAGETSLEAAIRELKEELGIDLdaDELRPILTI--RFDNGFDDIYLF 112

                         90       100
                 ....*....|....*....|....*..
gi 495778886 207 DYDSG--EIVIDQKELLDANWYRYDDL 231
Cdd:cd04693  113 RKDVDieDLTLQKEEVQDVKWVTLEEI 139

CDP-choline pyrophosphatase; CDP-choline pyrophosphatase catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467600 [Multi-domain] Cd Length: 129 Bit Score: 36.63 E-value: 3.90e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 139 DSILLAQHTRhrNGIHTVLAGFVEVGETLEQAVAREVMEESGIKV---KNLRYVTSQPWPFPQSLMTA----FMADYDSG 211
Cdd:cd18890   14 EEILLVKEKE--DGKWTLPGGWADVGYTPTEVAAKEVEEETGLEVspkKLLAILDKRKHPHPPQPTYVyklfILCEIEGG 91

                         90       100
                 ....*....|....*....|...
gi 495778886 212 EIViDQKELLDANWYRYDDLPLL 234
Cdd:cd18890   92 ELK-PSFETGEVRFFSENELPEL 113

nucleoside diphosphate-linked moiety X)) motif 17; Nucleoside diphosphate-linked moiety X)) motif 17 (EC 3.6.1.-) encoded by the NUDT17 gene on chromosome 1q21.1 and encodes an enzyme thought to hydrolyse some nucleoside diphosphate derivatives. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467576 [Multi-domain] Cd Length: 135 Bit Score: 36.50 E-value: 4.38e-03

                         10        20
                 ....*....|....*....|....*
gi 495778886 159 GFVEVGETLEQAVAREVMEESGIKV 183
Cdd:cd04694   37 GHVELGESLLEAGLRELQEETGLEV 61

Adp-ribose pyrophosphatase (ADPRase) found in Thermus thermophilus, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) such as found in extreme thermophile Thermus thermophilus (TtADPRase) catalyzes the hydrolysis of ADPR to AMP and ribose 5'-phosphate in the presence of Mg2+ and Zn2+ ions. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

Pssm-ID: 467608 [Multi-domain] Cd Length: 151 Bit Score: 36.33 E-value: 6.13e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 128 APCIIVAIRRDDSILLAQHTRHRNGIHT--VLAGFVEVGETLEQAVAREVMEESGIKvKNLRYVT---SQPwPFPQSLMT 202
Cdd:cd24160   21 ADAVAVLALREGRMLFVRQMRPAVGAATleIPAGLIDPGETPEEAARRELAEETGLS-GDLTYLTrfyVSP-GFCDEKLH 98

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 495778886 203 AFMADY-DSGEIVIDQKELLDANWYRyddlpllppPGTVARRLIEDTV 249
Cdd:cd24160   99 VFLAENlREVEAHPDEDEAIEVVWMR---------PEEVLERLRRGEV 137

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

Pssm-ID: 467594 Cd Length: 136 Bit Score: 35.91 E-value: 7.54e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 495778886 135 IRRDDSILLAqhtRHRNGIHTVL-AGFVEVGETLEQAVAREVMEESGIKVKNLRYV 189
Cdd:cd18883    7 IISDEHLLLA---RVKGDDKTFLpGGHIEIGESAEIALVRELREELGLSCKVGRYL 59

nucleoside triphosphatase NudI; Provisional

Pssm-ID: 185369 [Multi-domain] Cd Length: 141 Bit Score: 35.88 E-value: 7.66e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 135 IRRDDSILLAQHTRHRN---GIHTVLAGFVEVGETLEQAVAREVMEESGIKVkNLRYVTsqPWPFPQSLMTAFMADYDSG 211
Cdd:PRK15472  11 IQNDGAYLLCKMADDRGvfpGQWALSGGGVEPGERIEEALRREIREELGEQL-LLTEIT--PWTFRDDIRTKTYADGRKE 87

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 495778886 212 EI---------------VIDQKELLDANWYRYDDLPLL 234
Cdd:PRK15472  88 EIymiylifdcvsanrdVKINEEFQDYAWVKPEDLVHY 125

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

Pssm-ID: 467604 [Multi-domain] Cd Length: 134 Bit Score: 35.68 E-value: 7.79e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 131 IIVAIRRDDSILLAQHtrHRNGIHTVLAGF----VEVGETLEQAVAREVMEESGI---KVKNLRYVTSQPwPFPQSLMTA 203
Cdd:cd24156    6 MIVPILDDDHLLLIRE--YAAGTERYELGFpkglIDPGETPEEAANRELKEEIGFgarQLTLLRELSLAP-SYMSHKMHI 82


                 ...
gi 495778886 204 FMA 206
Cdd:cd24156   83 VLA 85

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

Pssm-ID: 467609 [Multi-domain] Cd Length: 137 Bit Score: 35.61 E-value: 8.53e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 495778886 130 CIIVAIRRDDSILLAQHTRHRNGIHT--VLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTS 191
Cdd:cd24161    6 VGVLPITDDGEVVLVEQYRYPLGGWSweIPAGGWPEGEDPEEAARRELREETGLRAERWTPLGR 69

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

Pssm-ID: 467589 [Multi-domain] Cd Length: 141 Bit Score: 35.80 E-value: 9.18e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 495778886 132 IVAIRRDDSI-LLAQHtR----HRNGIHTVLAGFVEVGETLEQAVAREVMEESGIKVKNLRYVTSQP-----WPFpqslm 201
Cdd:cd18877   23 LFAPAEDGGPhVLLQH-RawwtHQGGTWALPGGARDSGETPEAAALRETEEETGLDADTLRVVGTHVddhggWSY----- 96

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 495778886 202 TAFMADYDSG-EIVIDQKELLDANWYRYDD---LPLLPP 236
Cdd:cd18877   97 TTVLASAPEPlPVRPANEESVELRWVPLDEvesLPLHPG 135