NCBI Conserved Domain Search

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: 200.06 E-value: 3.52e-67

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582   2 RKTTLLFLHRPlEKQILLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPgdLLHVATIDFYFDGKPEf 81
Cdd:cd03427     1 KLTTLVFVLRG-DDRVLLGLKKRGFGAGKWNGFGGKVEPGETIEEAAVRELEEEAGLTATE--LEKVGRLKFEFPDDPE- 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  82 NQQVHAYLAEKWAGEPQESEEMRPEWHDYESIPFESMWIDDPHWLPRVLAGEKLNATFTF 141
Cdd:cd03427    77 AMDVHVFRADSWTGEPQETEEMRPQWFDLDDIPYDKMWPDDRLWLPLLLEGKKFKGRFDF 136

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: 80.74 E-value: 3.75e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582   3 KTTLLFLHRplEKQILLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSpgDLLHVATIDF-YFDGKPEf 81
Cdd:cd18886     1 KYTLCFIIR--DDEVLLLNRNKKPNMGKWNGVGGKLEPGESPEECAIREVFEETGLELE--DLQLRGIVTFpSFDGGED- 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1083480582  82 nQQVHAYLAEKWAGEPQES-EEMRPEWHDYESIPFESMWIDDPHWLPRVLAGEKLN-ATFTFD 142
Cdd:cd18886    76 -WLMYVFLAEAFSGELVESdREGILAWVPIDWLLNLPLWEGDRYFLPLLFDNEPPFeGKFHYD 137

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 77.33 E-value: 4.72e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  16 QILLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVatidfyFDGKPEFNQQVHAYLAEKWAG 95
Cdd:COG1051    19 RVLLVRRADEPGKGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGV------FDHPDRGHVVSVAFLAEVLSG 92

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1083480582  96 EPQ-ESEEMRPEWHDYESIPFESMWIDDPHWL 126
Cdd:COG1051    93 EPRaDDEIDEARWFPLDELPELAFTPADHEIL 124

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: 64.16 E-value: 7.96e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582   7 LFLHRplEKQILLAMKKR-GFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVAT-----------IDFY 74
Cdd:cd04683     5 LLLVR--GDEVLLLRRANtGYDDGWWHLPAGHVEAGETVRAAAVREAKEELGVEIDPEDLRLVHTmhrrsdggrerIDFF 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1083480582  75 FdgkpefnqqvhayLAEKWAGEPQESE-----EMRpeWHDYESIP 114
Cdd:cd04683    83 F-------------RATRWSGEPRNREpdkcaELR--WFPLDALP 112

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 64.04 E-value: 8.88e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582   2 RKTTLLFLHRPlEKQILLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATIDFYFDGKPEF 81
Cdd:pfam00293   3 RVAVGVVLLNE-KGRVLLVRRSKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRFPD 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1083480582  82 NQQVHAYLAEKWAGEPQ---ESEEMRPEWHDYESIPFESMWIDDPHWLPRV 129
Cdd:pfam00293  82 EHEILYVFLAEVEGELEpdpDGEVEEVRWVPLEELLLLKLAPGDRKLLPWL 132

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: 62.81 E-value: 1.25e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  14 EKQILLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATidfYFDGKPEFNQQVHAYLAEKW 93
Cdd:cd02883    11 EGRVLLVRRSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYE---FPDPDEGRHVVVLVFLARVV 87

                          90
                  ....*....|....*....
gi 1083480582  94 AGEP---QESEEMRPEWHD 109
Cdd:cd02883    88 GGEPpplDDEEISEVRWVP 106

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: 63.32 E-value: 1.49e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  16 QILLAMKKrgfGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATIDFYFDGKPEFnqQVHA--YLAEkW 93
Cdd:cd04690    13 RLLLVRKR---GTDAFYLPGGKREPGETPLQALVRELKEELGLDLDPDSLRFLGTFEAPAANEPGT--TVRMtcFTAD-Y 86

                          90       100
                  ....*....|....*....|..
gi 1083480582  94 AGEPQ---ESEEMRpeWHDYES 112
Cdd:cd04690    87 DGEPQpaaEIEELR--WLDPAD 106

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: 54.77 E-value: 2.52e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  14 EKQILLAmkKRGFGE---GKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATIDFyfdgkPEFNQQVHAYLA 90
Cdd:cd03425    11 DGRVLIA--QRPEGKhlaGLWEFPGGKVEPGETPEQALVRELREELGIEVEVGEPLGTVEHDY-----PDFHVRLHVYLC 83

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1083480582  91 EKWAGEPQ--ESEEMRpeWHDYESipfesmwIDDPHWLP 127
Cdd:cd03425    84 TLWSGEPQllEHQELR--WVTPEE-------LDDLDWLP 113

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: 51.76 E-value: 3.14e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  18 LLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATidfYFDGKPEFNQQVHAYLAEKWAGEP 97
Cdd:cd18880    14 LLLVKHRDEGGIFYILPGGGQEHGETLPEALKRECLEETGLDVEVGDLLFVRE---YIGPNKPVHQVELFFLCTLEGGEL 90

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1083480582  98 QESEEMRPEWHDYESIPFESmwIDDPHWLPRVLA 131
Cdd:cd18880    91 TLGSDPDLNQVGVEWIPLEE--LDSIRLYPAILR 122

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

Pssm-ID: 467587 [Multi-domain] Cd Length: 144 Bit Score: 51.42 E-value: 5.58e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  14 EKQILLAMKKRGFgegkWNGV---GGKLKDGEDILDALIREANEEISVTLSpgDLLHVATIDFYFDGKPEFnqQVHAYLA 90
Cdd:cd18875    13 EDRVLVLDRVKKD----WGGYtfpGGHVEPGESFVDSVIREVKEETGLTIK--NPELCGIKQWINPDGERY--IVFLYKT 84

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1083480582  91 EKWAGEPQESEEMRPEWHDYESIPFESMwIDDPHWLPRVLAGEKLnATFTFDQTG 145
Cdd:cd18875    85 DHFSGELLSSEEGELFWIPIEELKKLPL-ATDFDEMLRVFESDDL-SEFFYYREG 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: 51.19 E-value: 7.07e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582   2 RKTTLLFLHRPlEKQILLAMKKR-GFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATIDFYFDgkpe 80
Cdd:COG0494    13 RPAVVVVLLDD-DGRVLLVRRYRyGVGPGLWEFPGGKIEPGESPEEAALRELREETGLTAEDLELLGELPSPGYTD---- 87

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1083480582  81 fnQQVHAYLAEKWAGE-----PQESEEMRPEWHDYE 111
Cdd:COG0494    88 --EKVHVFLARGLGPGeevglDDEDEFIEVRWVPLD 121

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: 49.93 E-value: 1.61e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  18 LLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHvATIDFYFDGKpefnQQVHA-YLAEKWAGE 96
Cdd:cd04699    15 VLLLRRSRAGAGEWELPGGRLEPGESPEEALKREVKEETGLDVSVGELLD-TWTFELDPDK----GVFIVtYLCRLVGGE 89

                          90       100
                  ....*....|....*....|..
gi 1083480582  97 PQESEEMrpewHDYESIPFESM 118
Cdd:cd04699    90 VTLSDEH----EEYEWVTPEEL 107

8-oxo-dGTP diphosphatase MutT;

Pssm-ID: 182721 [Multi-domain] Cd Length: 129 Bit Score: 49.98 E-value: 1.82e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1083480582  29 GKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATIDFyfdgkPEFNQQVHAYLAEKWAGEPQESEEMRPEW 107
Cdd:PRK10776   31 GKWEFPGGKIEAGETPEQALIRELQEEVGITVQHATLFEKLEYEF-----PDRHITLWFWLVESWEGEPWGKEGQPGRW 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: 467570 [Multi-domain] Cd Length: 130 Bit Score: 49.47 E-value: 2.37e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  14 EKQILLAmkkRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATIDFYFDGKPeFNQQVHAYLAEKw 93
Cdd:cd04688    12 DGKVLLA---RGEDDDYYRLPGGRVEFGETSEDALVREFKEELGVEVEVVRLLFVVENFFTYDGKP-FHEIGFYYLVEL- 86

                          90       100
                  ....*....|....*....|....*...
gi 1083480582  94 agEPQESEEMRPEWHDYESIPFESMWID 121
Cdd:cd04688    87 --SDEALYEQDIFFLEEDGEKLEFRWIP 112

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: 46.35 E-value: 4.25e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  16 QILLAmkKRGF--GEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVAT-IDFYFDGKPEFNQQVHAYLAEK 92
Cdd:cd04673    13 RVLLV--RRGNppDAGLWSFPGGKVELGETLEDAALRELREETGLEAEVVGLLTVVDvIERDEAGRVRFHYVILDFLAEW 90


                  ....*.
gi 1083480582  93 WAGEPQ 98
Cdd:cd04673    91 VSGEPV 96

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: 45.25 E-value: 9.75e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  16 QILLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATIDFYFDGKpefnqqvH----AYLAE 91
Cdd:cd04678    15 KVLLGRRKGSHGAGTWALPGGHLEFGESFEECAAREVLEETGLEIRNVRFLTVTNDVFEEEGK-------HyvtiFVLAE 87

                          90       100
                  ....*....|....*....|....*....
gi 1083480582  92 KWAGEPQesEEMRP------EWHDYESIP 114
Cdd:cd04678    88 VDDGEPE--ENMEPdkcegwEWFSWDELP 114

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: 467574 [Multi-domain] Cd Length: 142 Bit Score: 44.86 E-value: 1.80e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582   3 KTTLLFLHRPLEKQILLamKKRGFGE----GKWN-GVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATIDFYFDG 77
Cdd:cd04692    27 RTVHVWLVNPEEGRLLL--QKRSANKddfpGLWDiSAAGHIDAGETYEEAAVRELEEELGLTVSPEDLIFLGVIREEVIG 104

                          90
                  ....*....|....*.
gi 1083480582  78 KPEFNQQ-VHAYLAEK 92
Cdd:cd04692   105 GDFIDNEfVHVYLYET 120

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: 44.22 E-value: 2.02e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  16 QILLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVA-TIDfyfdgkPEfnQQVH----AYLA 90
Cdd:cd04679    14 RLLLVLRLRAPEAGHWGLPGGKVDWLETVEDAVRREILEELGLEIELTRLLCVVdQID------AA--DGEHwvapVYLA 85

                          90
                  ....*....|....*...
gi 1083480582  91 EKWAGEPQeseEMRPEWH 108
Cdd:cd04679    86 EIFSGEPR---LMEPEKH 100

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: 43.01 E-value: 6.54e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1083480582  29 GKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATIDF 73
Cdd:cd18882    30 GYWGLFGGHLEPGETPEEAIRRELEEEIGYEPGEFRFFLLYTEDD 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: 467560 [Multi-domain] Cd Length: 137 Bit Score: 41.73 E-value: 2.09e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  10 HRPL------------EKQILLamKKRGFGeGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHV---ATIDFY 74
Cdd:cd04677     7 HRPLilvgaaviilneQGRILL--QKRTDT-GDWGLPGGAMELGESLEETARREVFEETGLTVEELELLGVysgKDLYYT 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1083480582  75 FDGKPEFNQQVHAYLAEKWAGEPQ----ESEEMRpeWHDYESIP 114
Cdd:cd04677    84 YPNGDEVYNVTAVYLVRDVSGELKvddeESLELR--FFSLDELP 125

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

Pssm-ID: 441052 [Multi-domain] Cd Length: 162 Bit Score: 41.72 E-value: 2.93e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582   7 LFLHRPlEKQILL---AMKKRGFGeGKW-NGVGGKLKDGEDILDALIREANEEISVTLSPgDLLHVATIDF--YFDGKPE 80
Cdd:COG1443    34 VFVFNS-DGRLLLqrrALTKDHWP-GLWdNTVCGHPRAGETYEEAAVRELEEELGITVDD-DLRPLGTFRYraVDANGLV 110

                          90       100
                  ....*....|....*....|...
gi 1083480582  81 FNQQVHAYLAEkWAGE--PQESE 101
Cdd:COG1443   111 ENEFCHVFVAR-LDGPltPQPEE 132

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: 40.36 E-value: 5.89e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1083480582  14 EKQILLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSP 62
Cdd:cd04691    11 EGKVLLVKRAYGPGKGRWTLPGGFVEEGETLDEAIVREVLEETGIDAKP 59

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: 39.97 E-value: 8.91e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  35 GGKLKDGEDILDALIREANEEISVTLSPGDLLHV-----ATIDFYFDGKPEFNQQVHAYLAEKWAGEPQESEEMRPEWHD 109
Cdd:cd04694    36 GGHVELGESLLEAGLRELQEETGLEVSDIQSLSLlglweSVYPTLLSIGLPKRHHIVVYYLVKLSESHENQEQLKLQEDE 115

                          90       100
                  ....*....|....*....|....
gi 1083480582 110 YEsipfESMWIdDPHWLPRVLAGE 133
Cdd:cd04694   116 VD----AAVWL-PKSLLAKLLEAE 134

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

Pssm-ID: 182536 [Multi-domain] Cd Length: 135 Bit Score: 39.72 E-value: 1.17e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  16 QILLAMKKRGFGE-GKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDllHVATIDFYFDGKpefNQQVHAYLAEKWA 94
Cdd:PRK10546   16 KILLAQRPAHSDQaGLWEFAGGKVEPGESQPQALIRELREELGIEATVGE--YVASHQREVSGR---RIHLHAWHVPDFH 90


                  ....
gi 1083480582  95 GEPQ 98
Cdd:PRK10546   91 GELQ 94

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: 39.58 E-value: 1.39e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  34 VGGKLKDGEDILDALIREANEE--ISVTLSPGDLlhvatidFYFDGKPEFNQQVHAYLAEkwagepqESEEMRPEWHDYE 111
Cdd:cd04663    31 PKGTVEPGESPEEAALRELAEEtgLTGARVVVDL-------GSHDEGFEELHQRWFFHLC-------LAGEPPERWEHHE 96

                          90       100
                  ....*....|....*....|....*....
gi 1083480582 112 S-------IPFESMWIdDPHWLPRVLAGE 133
Cdd:cd04663    97 TddgegggLRFEFFWV-PLAAAPPRLAAG 124

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 39.86 E-value: 2.88e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  16 QILLAMKKRG-FGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLL----------HVaTIDFYfdgkpefnqQ 84
Cdd:PRK08999   18 RILLARRPEGkHQGGLWEFPGGKVEPGETVEQALARELQEELGIEVTAARPLitvrhdypdkRV-RLDVR---------R 87

                          90
                  ....*....|...
gi 1083480582  85 VHAylaekWAGEP 97
Cdd:PRK08999   88 VTA-----WQGEP 95

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: 38.42 E-value: 2.93e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1083480582  14 EKQILLAMKKRGfgegKWNGVGGKLKDGEDILDALIREANEE 55
Cdd:cd04667    10 GDRILLVARRGG----RWLLPGGKIEPGESPLEAAIRELKEE 47

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: 38.66 E-value: 3.30e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1083480582  14 EKQILL---AMKKRGFGeGKW-NGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATI--DFYFD 76
Cdd:cd04693    40 DGEILIqqrSPDKKGFP-GMWeASTGGSVLAGETSLEAAIRELKEELGIDLDADELRPILTIrfDNGFD 107

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: 37.92 E-value: 5.08e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  36 GKLKDGEDILDALIREANEEISVTLSPGDLLHVATIDFYFDGKPEFNqQVHAYLAEKWAGE--PQESEEmrpewhdyesi 113
Cdd:cd03673    34 GKLEPGETPEEAAVREVEEETGLRVRLGRPLGTTRYTYTRKGKGILK-KVHYWLMRALGGEflPQPEEE----------- 101

                          90
                  ....*....|....
gi 1083480582 114 pfesmwIDDPHWLP 127
Cdd:cd03673   102 ------IDEVRWLP 109

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: 37.49 E-value: 7.90e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  35 GGKLKDGEDILDALIREANEEISvtLSPGDLLHVATidFYFDgkPEF-NQQVHAYLAE----KWAGEPQESEEMRPEWHD 109
Cdd:cd03424    35 AGKIDPGEDPEEAARRELEEETG--YTAGDLELLGS--FYPS--PGFsDERIHLFLAEdltpVSEQALDEDEFIEVVLVP 108


                  ..
gi 1083480582 110 YE 111
Cdd:cd03424   109 LE 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: 37.18 E-value: 8.41e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1083480582  31 WNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVAT----------IDFYFDGKP 79
Cdd:cd18876    25 WELPGGVVEAGESPLQAARREVREELGLDVPVGRLLAVDWvppagggddaVLFVFDGGV 83

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: 36.89 E-value: 1.02e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  14 EKQILLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVAT--IDFYFDGKPEFNQQVHAYLAE 91
Cdd:cd04686    11 NDKLLLIRKTRGPYQGRYDLPGGSQEFGESLEDALKREFAEETGMTVTSYDNLGVYDffVPWSDKELGDVHHIGVFYDVE 90

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1083480582  92 KWAGEPQESEEMR------PEWHDYESIPFESM 118
Cdd:cd04686    91 LLDNNISELLQFEgqdslgAVWIPLQDLTELNS 123

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: 36.75 E-value: 1.24e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1083480582   7 LFLHRPLEKQILLAMKKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHV 68
Cdd:cd18873     9 IFGFDDGELKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETGLKDIYLEQLGT 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: 467589 [Multi-domain] Cd Length: 141 Bit Score: 36.57 E-value: 1.89e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582   6 LLFLHRPLEKQILLAMKKRGF---GEGKWNGVGGKLKDGEDILDALIREANEEisVTLSPGDLLHVATID 72
Cdd:cd18877    21 LLLFAPAEDGGPHVLLQHRAWwthQGGTWALPGGARDSGETPEAAALRETEEE--TGLDADTLRVVGTHV 88

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: 36.07 E-value: 2.03e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582   6 LLFLHRPLEK-QILLAmkKRGFGEGKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATIDFY 74
Cdd:cd04664     4 LVVIYRKDEEgEVLLL--KRTDDGGFWQSVTGGIEDGETPWQAALRELKEETGLDPLELQLIDLNVSNFY 71

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: 35.96 E-value: 3.87e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  34 VGGKLKDGEDILDALIREANEEISVTlsPGDLLHVATidfYFD---GKPEFnqqVHAYLAE-------KWAGEPQESEEM 103
Cdd:cd24155    81 VAGMIDAGETPEDVARREAEEEAGLT--LDALEPIAS---YYPspgGSTER---VHLYLGLvdlsdlgGIHGLAEEGEDI 152

                          90       100
                  ....*....|....*....|.
gi 1083480582 104 RPEWhdyesIPFESM--WIDD 122
Cdd:cd24155   153 RVHV-----VPFDEAmaLLDD 168

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: 35.25 E-value: 4.50e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083480582  29 GKWNGVGGKLKDGEDILDALIREANEEISVTLSPGDLLHVATID----------FYFDgkpefnqqvHAYLAEKWAGEPQ 98
Cdd:cd18879    41 GRWTPVTGIVEPGEQPADAAVREVLEETGVDVEVERLASVGASPpvtypngdqcQYLD---------LTFRCRPVGGEAR 111

                          90       100
                  ....*....|....*....|
gi 1083480582  99 ----ESEEMRpeWHDYESIP 114
Cdd:cd18879   112 vnddESLEVG--WFPVDALP 129

thiamine diphosphokinase Tnr3 from Schizosaccharomyces pombe and similar proteins; Tnr3 is a bifunctional enzyme composed of a C-terminal thiamine pyrophosphokinase domain, which transfers pyrophosphate from ATP to thiamine and an N-terminal NUDIX hydrolase domain that converts oxidized derivatives of thiamine diphosphate (oxothiamine and oxythiamine) to their respective monophosphates. 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, 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: 467544 Cd Length: 153 Bit Score: 35.16 E-value: 6.08e-03

                          10        20
                  ....*....|....*....|....*...
gi 1083480582  29 GKW-NGVGGKLKDGEDILDALIREANEE 55
Cdd:cd03676    37 GKLdNLVAGGVPAGESPLETLVREAEEE 64

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: 35.17 E-value: 6.16e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1083480582  36 GKLKDGEDILDALIREANEEISVTlspGDLlhvaTIDFYFDGKPEF-NQQVHAYLAEKW---AGEPQESEEMRPEWHD 109
Cdd:cd24160    54 GLIDPGETPEEAARRELAEETGLS---GDL----TYLTRFYVSPGFcDEKLHVFLAENLrevEAHPDEDEAIEVVWMR 124

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: 34.57 E-value: 7.08e-03

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1083480582  30 KWNGV----GGKLKDGEDILDALIREANEEISVTLSP 62
Cdd:cd18874    23 KWNDLygipGGKVEWGETLEEALKREVKEETGLDITD 59

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: 34.47 E-value: 8.26e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1083480582  31 WNGVGGKLKDGEDILDALIREANEEISVTLSPGDLL-HVA--TIDFYFDGKP 79
Cdd:cd04685    30 WFTPGGGVEPGESPEQAAVRELREETGLRLEPDDLGgPVWrrRAVFDFSGET 81