NAD(+) diphosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811  23 DAKKTADSLWLLVKGNHTLFANssPEVVYLAYQQvAHLDLTQAILLGSnKQDNAVFALDVTELeesllatiiDGAQFADI 102
Cdd:PRK00241    6 DLEALDAGWWVVSHEQQLWLPD--GELPFGAAAN-LDLPGLRALQIGE-WQGEPVWLVRQDPL---------RGHEMGSL 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 103 RQFgtqVALEDGSNAALARG--LCYWHATHSFCGRCGTKNHLVEAGHSRLCdnPACLHQTFPRTDPAVIMVVTRTfsdgi 180
Cdd:PRK00241   73 RQL---LDLDDGLFQLLGRAvqLAEFYRSHRFCGYCGHPMHPSKTEWAMLC--PHCRERYYPRIAPCIIVAVRRG----- 142

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 181 ERCLLGRQATWPKGLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPWPFPSSIMLGFIATASSDEISTEQD 260
Cdd:PRK00241  143 DEILLARHPRHRNGVYTVLAGFVEVGETLEQCVAREVMEESGIKVKNLRYVGSQPWPFPHSLMLGFHADYDSGEIVFDPK 222

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1222442811 261 ELEDAKWFSREELaqfkdwhhqgehLKLPRADSISRYLIEYW 302
Cdd:PRK00241  223 EIADAQWFRYDEL------------PLLPPSGTIARRLIEDT 252

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 166 PAVIMVVTRTFsdgiERCLLGRQATWP-KGLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPWPFPS---- 240
Cdd:pfam00293   4 VAVGVVLLNEK----GRVLLVRRSKKPfPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFdgrf 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1222442811 241 ----SIMLGFIATASSDEISTEQDELEDAKWFSREELAQFKDWHHQGEHLKL 288
Cdd:pfam00293  80 pdehEILYVFLAEVEGELEPDPDGEVEEVRWVPLEELLLLKLAPGDRKLLPW 131

NAD(+) diphosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811  23 DAKKTADSLWLLVKGNHTLFANssPEVVYLAYQQvAHLDLTQAILLGSnKQDNAVFALDVTELeesllatiiDGAQFADI 102
Cdd:PRK00241    6 DLEALDAGWWVVSHEQQLWLPD--GELPFGAAAN-LDLPGLRALQIGE-WQGEPVWLVRQDPL---------RGHEMGSL 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 103 RQFgtqVALEDGSNAALARG--LCYWHATHSFCGRCGTKNHLVEAGHSRLCdnPACLHQTFPRTDPAVIMVVTRTfsdgi 180
Cdd:PRK00241   73 RQL---LDLDDGLFQLLGRAvqLAEFYRSHRFCGYCGHPMHPSKTEWAMLC--PHCRERYYPRIAPCIIVAVRRG----- 142

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 181 ERCLLGRQATWPKGLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPWPFPSSIMLGFIATASSDEISTEQD 260
Cdd:PRK00241  143 DEILLARHPRHRNGVYTVLAGFVEVGETLEQCVAREVMEESGIKVKNLRYVGSQPWPFPHSLMLGFHADYDSGEIVFDPK 222

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1222442811 261 ELEDAKWFSREELaqfkdwhhqgehLKLPRADSISRYLIEYW 302
Cdd:PRK00241  223 EIADAQWFRYDEL------------PLLPPSGTIARRLIEDT 252

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 166 PAVIMVVTRTFsdgiERCLLGRQATWP-KGLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPWPFPS---- 240
Cdd:pfam00293   4 VAVGVVLLNEK----GRVLLVRRSKKPfPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFdgrf 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1222442811 241 ----SIMLGFIATASSDEISTEQDELEDAKWFSREELAQFKDWHHQGEHLKL 288
Cdd:pfam00293  80 pdehEILYVFLAEVEGELEPDPDGEVEEVRWVPLEELLLLKLAPGDRKLLPW 131

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 1222442811 166 PAVIMVVTrtfsDGIERCLLGRQATWP-KGLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPWPFP----S 240
Cdd:cd02883     1 VAVGAVVF----DDEGRVLLVRRSDGPgPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPdegrH 76

                          90       100       110
                  ....*....|....*....|....*....|
gi 1222442811 241 SIMLGFIATASSDEISTEQ-DELEDAKWFS 269
Cdd:cd02883    77 VVVLVFLARVVGGEPPPLDdEEISEVRWVP 106

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 167 AVIMVVTRTfsdgiERCLLGRQATWP--KGLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPWP-FPSSIM 243
Cdd:COG0494    16 VVVVLLDDD-----GRVLLVRRYRYGvgPGLWEFPGGKIEPGESPEEAALRELREETGLTAEDLELLGELPSPgYTDEKV 90

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1222442811 244 LGFIATASSDEIS---TEQDELEDAKWFSREELAQF 276
Cdd:COG0494    91 HVFLARGLGPGEEvglDDEDEFIEVRWVPLDEALAL 126

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 181 ERCLLGRQATWPKGLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPWPFPSSIMLGFIATASSDEIstEQD 260
Cdd:cd18884    20 GHIVLARNKAWPEGWYGLVTGFLEAGESPEEAVLREVKEELGLDGHEAKFIGHYAFPERNQLIIAYHVRARGNVK--LNE 97

                          90
                  ....*....|....*..
gi 1222442811 261 ELEDAKWFSREELAQFK 277
Cdd:cd18884    98 ELDDYKIVPIDKLRPWP 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 201 GFVDPGETLEQTVIREVKEEAGITVEkAEYIAS----QPWPFPSSIMLgFIAT---ASSDEISTEQDELEDAKWFSREEL 273
Cdd:cd04670    34 GLVDPGEDIGEAAVREVFEETGIDTE-FVSILGfrhqHPGRFGKSDLY-FVCRlrpLSDEEIKICPEEIAEAKWMPLEEY 111

                          90
                  ....*....|....
gi 1222442811 274 AQFKDWHHQGEHLK 287
Cdd:cd04670   112 LKQPNVSQINKLVA 125

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 1222442811 171 VVTRTFSDGIERCLLGRQA----TWPKGLysslagfVDPGETLEQTVIREVKEEAGITVEKAEYIASQPWPFPSSIMLG- 245
Cdd:cd03673     7 VVWRGRGGGGEVLLIHRPRyddwSLPKGK-------LEPGETPEEAAVREVEEETGLRVRLGRPLGTTRYTYTRKGKGIl 79

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1222442811 246 -----FIATASSDEISTEQ-DELEDAKWFSREELAQ 275
Cdd:cd03673    80 kkvhyWLMRALGGEFLPQPeEEIDEVRWLPPDEARR 115

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 166 PAVIMVVTRtfsdGIERCLLGRQATwpKGLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYI---ASQPWPFP--- 239
Cdd:cd18879    19 PGVTAVVLR----DAGRVLLVRRAD--NGRWTPVTGIVEPGEQPADAAVREVLEETGVDVEVERLAsvgASPPVTYPngd 92

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1222442811 240 -SSIM-LGFIATASSDEISTEQDELEDAKWFSREEL 273
Cdd:cd18879    93 qCQYLdLTFRCRPVGGEARVNDDESLEVGWFPVDAL 128

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 198 SLAGF-------VDPGETLEQTVIREVKEEAGITVEKAEYIA--SQPWPFPSSIMLGFIATASSDEI-STEQDELedaKW 267
Cdd:cd03425    24 HLAGLwefpggkVEPGETPEQALVRELREELGIEVEVGEPLGtvEHDYPDFHVRLHVYLCTLWSGEPqLLEHQEL---RW 100

                          90
                  ....*....|..
gi 1222442811 268 FSREELAQFkDW 279
Cdd:cd03425   101 VTPEELDDL-DW 111

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 176 FSDGIERCLLGRQatwPK-GLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPW-----------PFPSS-- 241
Cdd:cd03674     9 VNPDRGKVLLVHH---RKlGRWLQPGGHVEPDEDPLEAALREAREETGLDVELLSPLSPDPLdidvhpipanpGEPAHlh 85

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1222442811 242 IMLGFIATASSDEISTEQDELEDAKWFSREELAQ 275
Cdd:cd03674    86 LDVRYLAVADGDEALRKSDESSDVRWFPLDELEE 119

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 178 DGIERCLLGRQAT-WPKGLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIA-------SQPWPFPSSImlgFIAT 249
Cdd:cd03427    10 RGDDRVLLGLKKRgFGAGKWNGFGGKVEPGETIEEAAVRELEEEAGLTATELEKVGrlkfefpDDPEAMDVHV---FRAD 86

                          90       100
                  ....*....|....*....|....*
gi 1222442811 250 ASSDEIsTEQDELEdAKWFSREELA 274
Cdd:cd03427    87 SWTGEP-QETEEMR-PQWFDLDDIP 109

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 1222442811 201 GFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPWPFPSS---IMLGFIATASSDE-ISTEQDELEdakWFSREEL 273
Cdd:cd18875    34 GHVEPGESFVDSVIREVKEETGLTIKNPELCGIKQWINPDGeryIVFLYKTDHFSGElLSSEEGELF---WIPIEEL 107

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 171 VVTRTFSDGIERCLLGRQAT--W--PKGLysslagfVDPGETLEQTVIREVKEEAGITV--------EKAEYIASqpWPF 238
Cdd:cd03428     8 IIYRRDNGEIEFLLLQHSYGghWdfPKGH-------VEPGESELETALRETKEETGLTVddlppgfrETLTYSFK--EGV 78

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1222442811 239 PSSIMLgFIATASSDEISTEQDELEDAKWFSREE 272
Cdd:cd03428    79 EKTVVY-FLAELTPDVEVKLSEEHQDYKWLPYEE 111

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 200 AGFVDPGETLEQTVIREVKEEAGITVEKAEYIASQpWPFP---SSIMLGFIATASSDEISTEQ---DELEDAKWF--SRE 271
Cdd:cd24155    82 AGMIDAGETPEDVARREAEEEAGLTLDALEPIASY-YPSPggsTERVHLYLGLVDLSDLGGIHglaEEGEDIRVHvvPFD 160

                          90
                  ....*....|...
gi 1222442811 272 ELAQfkdWHHQGE 284
Cdd:cd24155   161 EAMA---LLDDGE 170

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 201 GFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPW-----PFPSSIMLG----FIATASSDEIST------EQDELEDA 265
Cdd:cd04685    35 GGVEPGESPEQAAVRELREETGLRLEPDDLGGPVWRrravfDFSGETVRQderfFLVRVPAFEVDTagwtdlERAVIDGH 114

                          90
                  ....*....|
gi 1222442811 266 KWFSREELAQ 275
Cdd:cd04685   115 RWWSLAELAA 124

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 167 AVIMVVTRTFSDGIERCLLGRQATWPKGLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIA--SQPW--PFPSSI 242
Cdd:cd18873     4 TVDCVIFGFDDGELKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETGLKDIYLEQLGtfGDPDrdPRGRVI 83

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1222442811 243 MLGFIA-TASSDEISTEQDELEDAKWFSREEL 273
Cdd:cd18873    84 SVAYLAlVPEEDLAPKAGDDAAEARWFPVDEL 115

Isopentenyldiphosphate isomerase [Lipid transport and metabolism]; Isopentenyldiphosphate isomerase is part of the Pathway/BioSystem: Isoprenoid biosynthesis

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 174 RTFS----DGIERCLLGRQA----TWPkGLYS-SLAGFVDPGETLEQTVIREVKEEAGITVE-------KAEYIAsqpwP 237
Cdd:COG1443    30 RAFSvfvfNSDGRLLLQRRAltkdHWP-GLWDnTVCGHPRAGETYEEAAVRELEEELGITVDddlrplgTFRYRA----V 104

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1222442811 238 FPSSIM---LG--FIATaSSDEISTEQDELEDAKWFSREELAQ 275
Cdd:COG1443   105 DANGLVeneFChvFVAR-LDGPLTPQPEEVAEVRWVTLEELLA 146

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 201 GFVDPGETLEQTVIREVKEEAGITVEKA-----EYIASQPWPFPSSIMLGFIATASSDEIST---EQDELEDAKWFSREE 272
Cdd:cd18876    30 GVVEAGESPLQAARREVREELGLDVPVGrllavDWVPPAGGGDDAVLFVFDGGVLTPEQAAAirlQDEELSAYRFVTPEE 109

                  ...
gi 1222442811 273 LAQ 275
Cdd:cd18876   110 AAE 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 181 ERCLLGRQATWP-KGLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAE----YIASQPWPFPSSIMLGFIA------T 249
Cdd:cd04686    12 DKLLLIRKTRGPyQGRYDLPGGSQEFGESLEDALKREFAEETGMTVTSYDnlgvYDFFVPWSDKELGDVHHIGvfydveL 91

                          90       100
                  ....*....|....*....|....*..
gi 1222442811 250 ASSDEISTEQDELED---AKWFSREEL 273
Cdd:cd04686    92 LDNNISELLQFEGQDslgAVWIPLQDL 118

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 194 GLYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPW------PFPSSIMLGFIATASSDEISTEQDELEDAKW 267
Cdd:cd18889    23 GRWSLPGGWVDVNQSIKENTIKEAKEEAGLDVEPKRIIAVLDRnkhnkpPYAYGIYKIFVLCELLGGEFQPNIETIESGY 102

                  ....*.
gi 1222442811 268 FSREEL 273
Cdd:cd18889   103 FSLDEL 108

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1222442811 201 GFVDPGETLEQTVIREVKEEAGITVEKAEYIASQPWPFPSS---IMLGFIATASSDEIsTEQDELEDAKWFSREELA 274
Cdd:cd04699    33 GRLEPGESPEEALKREVKEETGLDVSVGELLDTWTFELDPDkgvFIVTYLCRLVGGEV-TLSDEHEEYEWVTPEELA 108

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 196 YSSLAGFVDPGETLEQTVIREVKEEAGITVEKAEYIA---------SQPWpfpSSIMLGFIATASSDE-------ISTEQ 259
Cdd:cd04688    26 YRLPGGRVEFGETSEDALVREFKEELGVEVEVVRLLFvvenfftydGKPF---HEIGFYYLVELSDEAlyeqdifFLEED 102

                          90
                  ....*....|....*.
gi 1222442811 260 DELEDAKWFSREELAQ 275
Cdd:cd04688   103 GEKLEFRWIPLEELDE 118

ADP-ribose pyrophosphatase NudF; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1222442811 195 LYSSLAGFVDPGETLEQTVIREVKEEAGITVEKAE----YIASqpwpfP------SSIMLGFIATASSDEISTEQDELED 264
Cdd:PRK10729   83 LLEMVAGMIEEGESVEDVARREAIEEAGLIVGRTKpvlsYLAS-----PggtserSSIMVGEVDATTASGIHGLADENED 157

                          90       100
                  ....*....|....*....|.
gi 1222442811 265 AK--WFSREELAQfkdWHHQG 283
Cdd:PRK10729  158 IRvhVVSREQAYQ---WVEEG 175

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 1222442811 201 GFVDPGETLEQTVIREVKEEAGITVEKAEYIAS---QPWPFPSSIMLGFIA-TASSDEISTEQDELEDAKWFSREEL 273
Cdd:cd04680    30 GGVDKGETAEEAARRELREEAGVVLTGPPRLFGvyfNRRVSPRDHVALYRVrEFEQTEPPEPNGEIAEAGFFALDAL 106