putative NUDIX hydrolase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344217763  31 SAAVLVPLCSvRGVPALLYTLRSSRLTgRHKGDVSFPGGKCDPADQDVVHTALRETREElgLAVPEE--HVWGLLRPVYD 108
Cdd:PRK10707  31 QAAVLIPIVR-RPQPTLLLTQRSIHLR-KHAGQVAFPGGAVDPTDASLIATALREAQEE--VAIPPSavEVIGVLPPVDS 106

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344217763 109 PQKATVVPVlagVGPLDPQ-SLRPNSEEVDEVFALPLAHLLQTQNQGYTHFCRGGH-FRYTLPVFLHgpHRVWGLTA-VI 185
Cdd:PRK10707 107 STGYQVTPV---VGIIPPDlPYRANEDEVAAVFEMPLAEALHLGRYHPLDIYRRGQsHRVWLSWYEQ--YFVWGMTAgII 181

                 ....*.
gi 344217763 186 TEFALQ 191
Cdd:PRK10707 182 RELALQ 187

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344217763   32 AAVLVPLCSVRGvpALLYTLRSSRltgRHKGDVSFPGGKCDPaDQDVVHTALRETREELGLAVPEEHVWGLLRPVY---- 107
Cdd:pfam00293   4 VAVGVVLLNEKG--RVLLVRRSKK---PFPGWWSLPGGKVEP-GETPEEAARRELEEETGLEPELLELLGSLHYLApfdg 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 344217763  108 -DPQKATVVPVLagVGPLDPQSLRPNSEEVDEVFALPLAHLL 148
Cdd:pfam00293  78 rFPDEHEILYVF--LAEVEGELEPDPDGEVEEVRWVPLEELL 117

putative NUDIX hydrolase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344217763  31 SAAVLVPLCSvRGVPALLYTLRSSRLTgRHKGDVSFPGGKCDPADQDVVHTALRETREElgLAVPEE--HVWGLLRPVYD 108
Cdd:PRK10707  31 QAAVLIPIVR-RPQPTLLLTQRSIHLR-KHAGQVAFPGGAVDPTDASLIATALREAQEE--VAIPPSavEVIGVLPPVDS 106

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344217763 109 PQKATVVPVlagVGPLDPQ-SLRPNSEEVDEVFALPLAHLLQTQNQGYTHFCRGGH-FRYTLPVFLHgpHRVWGLTA-VI 185
Cdd:PRK10707 107 STGYQVTPV---VGIIPPDlPYRANEDEVAAVFEMPLAEALHLGRYHPLDIYRRGQsHRVWLSWYEQ--YFVWGMTAgII 181

                 ....*.
gi 344217763 186 TEFALQ 191
Cdd:PRK10707 182 RELALQ 187

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344217763  58 GRHKGDVSFPGGKCDPADqDVVHTALRETREELGLAVPEEHVWG-LLRPVYDPQKATVVpVLAGVGPLDPQSLRPNsEEV 136
Cdd:COG0494   36 GVGPGLWEFPGGKIEPGE-SPEEAALRELREETGLTAEDLELLGeLPSPGYTDEKVHVF-LARGLGPGEEVGLDDE-DEF 112

                         90
                 ....*....|...
gi 344217763 137 DEVFALPLAHLLQ 149
Cdd:COG0494  113 IEVRWVPLDEALA 125

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344217763  31 SAAVLVplcsVRGVPALLYTLRSSrltGRHKGDVSFPGGKCDPaDQDVVHTALRETREELGLAVPEEHVWGLLRPVYDPQ 110
Cdd:cd02883    2 AVGAVV----FDDEGRVLLVRRSD---GPGPGGWELPGGGVEP-GETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDE 73

                         90       100
                 ....*....|....*....|....*....
gi 344217763 111 KATVVPVLAGVGPLDPQSLRPNSEEVDEV 139
Cdd:cd02883   74 GRHVVVLVFLARVVGGEPPPLDDEEISEV 102

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 344217763  74 ADQDVVHTALRETREELGLAVPEEHVW--GLLRPVYDPQKAT---VVPVLAGVGPLDPQSLRPNSEEVDEVFALPL 144
Cdd:cd04692   67 AGETYEEAAVRELEEELGLTVSPEDLIflGVIREEVIGGDFIdneFVHVYLYETDRPLEEFKLQPEEVAGVVFVDL 142

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344217763  66 FPGGKCDPaDQDVVHTALRETREELGLAVPEEHVWGLL---RPVY-------DPQKATVVPVLAGVGPLDPQ---SLRPN 132
Cdd:cd04694   34 PPGGHVEL-GESLLEAGLRELQEETGLEVSDIQSLSLLglwESVYptllsigLPKRHHIVVYYLVKLSESHEnqeQLKLQ 112

                         90       100
                 ....*....|....*....|..
gi 344217763 133 SEEVDEVFALP---LAHLLQTQ 151
Cdd:cd04694  113 EDEVDAAVWLPkslLAKLLEAE 134

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344217763  47 LLYTLRSSRL------------TGRHKGDVSFPGGKCDPaDQDVVHTALRETREELGLAVPEEHvWGLLRPVydPQKA-T 113
Cdd:COG4119    9 LLYRRRDGGLevllvhpggpfwARKDEGAWSIPKGEYEP-GEDPLAAARREFAEETGVPAPDGP-FIPLGEV--RQKSgK 84

                         90       100
                 ....*....|....*....|
gi 344217763 114 VVPVLAGVGPLDPQSLRPNS 133
Cdd:COG4119   85 VVTAWAVEGDLDPAAIVSNT 104

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344217763  59 RHKGDVSFPGGKCDPaDQDVVHTALRETREELGLAV----PEEHVWgllRPVYDPQKATVVPVL-----AGVGPLDPQSl 129
Cdd:cd03673   24 PRYDDWSLPKGKLEP-GETPEEAAVREVEEETGLRVrlgrPLGTTR---YTYTRKGKGILKKVHywlmrALGGEFLPQP- 98

                         90       100
                 ....*....|....*....|
gi 344217763 130 rpnSEEVDEVFALPLAHLLQ 149
Cdd:cd03673   99 ---EEEIDEVRWLPPDEARR 115

ADP-ribose pyrophosphatase, UDP-glucose pyrophosphatase, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) ( NUDIX (Nucleoside diphosphate-linked moiety X)) motif 5; Nudt5) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344217763  66 FPGGKCDPaDQDVVHTALRETREELGLAVPEehvWGLLRPVY-DP----QKATVvpVLA-GVGPLDPQSLRPNseEVDEV 139
Cdd:cd03424   33 LPAGKIDP-GEDPEEAARRELEEETGYTAGD---LELLGSFYpSPgfsdERIHL--FLAeDLTPVSEQALDED--EFIEV 104

                         90
                 ....*....|....*
gi 344217763 140 FALPLAHLLQTQNQG 154
Cdd:cd03424  105 VLVPLEEALEMIEDG 119

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 344217763  34 VLVPLCSVRGVPALLyTLRSSrlTGRHKGDVSFPGGKCDPaDQDVVHTALRETREELGLAVPEEHVW 100
Cdd:cd04683    1 VDVHLLLVRGDEVLL-LRRAN--TGYDDGWWHLPAGHVEA-GETVRAAAVREAKEELGVEIDPEDLR 63

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

                         10        20        30
                 ....*....|....*....|....*....|..
gi 344217763  66 FPGGKCDPADQDVvHTALRETREELGLAVPEE 97
Cdd:cd04690   27 LPGGKREPGETPL-QALVRELKEELGLDLDPD 57

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 344217763  66 FPGGKCDP--ADQDvvhtAL-RETREELGLAVPEEHVWGLLRPVYD 108
Cdd:cd03425   31 FPGGKVEPgeTPEQ----ALvRELREELGIEVEVGEPLGTVEHDYP 72