NCBI Conserved Domain Search

GDP-mannose mannosyl hydrolase;

Pssm-ID: 237966 [Multi-domain] Cd Length: 159 Bit Score: 330.56 E-value: 2.27e-118

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971   1 MFLRQEDFATVVRSTPLVSLDFIAENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQ 80
Cdd:PRK15434   1 MFLRQEDFATVVRSTPLISLDFIVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQ 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 446401971  81 FYGVWQHFYDDNFSGTDFTTHYVVLGFRFRVAEEDLILPDEQHDDYRWLTPDALLASNDVHANSRAYFLAEKRAGVPGL 159
Cdd:PRK15434  81 FYGVWQHFYDDNFSGTDFTTHYVVLGFRLRVAEEDLLLPDEQHDDYRWLTPDALLASDNVHANSRAYFLAEKRAGVPGL 159

GDP-mannose glycosyl hydrolase; GDP-mannose glycosyl hydrolase, also known as GDP-mannose mannosyl hydrolase/GDPMH, is a member of the NUDIX hydrolase superfamily. This class of enzymes is unique from other members of the superfamily in two aspects. First, it contains a modified NUDIX signature sequence. The slight changes to the conserved sequence motif, GX5EX7REUXEEXGU, where U = I, L or V), are believed to contribute to the removal of all magnesium binding sites but one, retaining only the metal site that coordinates the pyrophosphate of the substrate. Secondly, it is not a pyrophosphatase that substitutes at a phosphorus; instead, it hydrolyzes nucleotide sugars such as GDP-mannose to GDP and mannose, cleaving the phosphoglycosyl bond by substituting at a carbon position. GDP-mannose provides mannosyl components for cell wall synthesis and is required for the synthesis of other glycosyl donors (such as GDP-fucose and colitose) for the cell wall. The importance of GDP-sugar hydrolase activities is thus closely related to the regulation of cell wall biosynthesis. Enzymes in this family are believed to regulate the concentration of GDP-mannose and GDP-glucose in the bacterial cell wall.

Pssm-ID: 467536 [Multi-domain] Cd Length: 146 Bit Score: 254.47 E-value: 2.12e-88

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971   3 LRQEDFATVVRSTPLVSLDFIAENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQFY 82
Cdd:cd03430    1 LPEEDFKTVVENTPLVSIDLIIRNEDGEILLGKRNNRPAQGYWFVPGGRILKNETLDDAFKRIAREELGLEVTINAAEFL 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 446401971  83 GVWQHFYDDNFSGTDFTTHYVVLGFRFRVAEEDLILPDEQHDDYRWLTPDALLASNDVHANSRAYF 148
Cdd:cd03430   81 GVYEHFYDDNFSGEDFSTHYVVLAYRLKLDEGLLLLPDDQHDEYRWFTIDELLANDDVHPYTKAYF 146

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 83.10 E-value: 3.97e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  14 STPLVSLDFIAENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYddnf 93
Cdd:COG1051    3 KVPKVAVDAVIFRKDGRVLLVRRADEPGKGLWALPGGKVEPGETPEEAALRELREETGLE--VEVLELLGVFDHPD---- 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 446401971  94 sgtdfTTHYVVLGFRFRVAEEDLILPDEqHDDYRWLTPDALLA 136
Cdd:COG1051   77 -----RGHVVSVAFLAEVLSGEPRADDE-IDEARWFPLDELPE 113

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 81.38 E-value: 2.30e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971   23 IAENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITagQFYGVWQHFYDDNFSGTDftTHY 102
Cdd:pfam00293   9 VLLNEKGRVLLVRRSKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELL--ELLGSLHYLAPFDGRFPD--EHE 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 446401971  103 VVLGFRFRVAEEDLILPDEQHDDYRWLTPDALLASNDVHANSRAY 147
Cdd:pfam00293  85 ILYVFLAEVEGELEPDPDGEVEEVRWVPLEELLLLKLAPGDRKLL 129

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: 70.13 E-value: 2.49e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  23 IAENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNfsgtdfTTHY 102
Cdd:cd02883    6 VVFDDEGRVLLVRRSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLD--VEVLRLLGVYEFPDPDE------GRHV 77

                         90       100
                 ....*....|....*....|....*....
gi 446401971 103 VVLGFRFRVAEEDL-ILPDEQHDDYRWLT 130
Cdd:cd02883   78 VVLVFLARVVGGEPpPLDDEEISEVRWVP 106

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: 64.07 E-value: 6.96e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  29 GEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNFSGTDFttHYVVLGFR 108
Cdd:cd04673   12 GRVLLVRRGNPPDAGLWSFPGGKVELGETLEDAALRELREETGLE--AEVVGLLTVVDVIERDEAGRVRF--HYVILDFL 87

                         90       100       110
                 ....*....|....*....|....*....|..
gi 446401971 109 FRVAEEDLILPDEQhDDYRWLTPDALLASNDV 140
Cdd:cd04673   88 AEWVSGEPVAGDDA-LDARWFSLEELDGLPLT 118

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: 59.17 E-value: 4.25e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  29 GEFLLGKRtNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDnfsgtdfTTHYVVLGFR 108
Cdd:cd04699   13 GRVLLLRR-SRAGAGEWELPGGRLEPGESPEEALKREVKEETGLD--VSVGELLDTWTFELDP-------DKGVFIVTYL 82

                         90       100
                 ....*....|....*....|....*.
gi 446401971 109 FRVAEEDLILPDEqHDDYRWLTPDAL 134
Cdd:cd04699   83 CRLVGGEVTLSDE-HEEYEWVTPEEL 107

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: 58.12 E-value: 2.20e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  23 IAENSRGEFLLGKRTNRPAQ-GYWFVPGGRVQKDETLEAAFERLTMAELGLRLpitagqfyGVWQHFYD-DNFSGTDFTT 100
Cdd:COG0494   19 VLLDDDGRVLLVRRYRYGVGpGLWEFPGGKIEPGESPEEAALRELREETGLTA--------EDLELLGElPSPGYTDEKV 90

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 446401971 101 HYVVLGFRFRVAEEDLILPDEqHDDYRWLTPDALLA 136
Cdd:COG0494   91 HVFLARGLGPGEEVGLDDEDE-FIEVRWVPLDEALA 125

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

Pssm-ID: 467562 [Multi-domain] Cd Length: 126 Bit Score: 56.93 E-value: 3.94e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  28 RGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNfsgtdfTTHYVVLGF 107
Cdd:cd04679   12 DGRLLLVLRLRAPEAGHWGLPGGKVDWLETVEDAVRREILEELGLE--IELTRLLCVVDQIDAAD------GEHWVAPVY 83

                         90       100
                 ....*....|....*....|....*...
gi 446401971 108 RFRVAE-EDLILPDEQHDDYRWLTPDAL 134
Cdd:cd04679   84 LAEIFSgEPRLMEPEKHGGIGWFALDAL 111

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: 56.80 E-value: 4.18e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  26 NSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQ-HFYDDNFsgtdfttHYVV 104
Cdd:cd04678   11 NDDGKVLLGRRKGSHGAGTWALPGGHLEFGESFEECAAREVLEETGLE--IRNVRFLTVTNdVFEEEGK-------HYVT 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 446401971 105 LGFRFRVAEEDL--ILPDEQHDDYRWLTPDALLASNDVHANSRAYF 148
Cdd:cd04678   82 IFVLAEVDDGEPeeNMEPDKCEGWEWFSWDELPPLRPLFLPLANLL 127

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: 56.31 E-value: 7.40e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  29 GEFLLGKRT-NRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNfsgtdfttHYVVLGF 107
Cdd:cd03425   12 GRVLIAQRPeGKHLAGLWEFPGGKVEPGETPEQALVRELREELGIE--VEVGEPLGTVEHDYPDF--------HVRLHVY 81

                         90       100
                 ....*....|....*....|....*....
gi 446401971 108 RFRVAEEDLILPDeqHDDYRWLTPDALLA 136
Cdd:cd03425   82 LCTLWSGEPQLLE--HQELRWVTPEELDD 108

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

Pssm-ID: 467586 [Multi-domain] Cd Length: 125 Bit Score: 50.75 E-value: 9.49e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  16 PLVSLDFIAENSRGEFLLGKRTNrpAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNFSG 95
Cdd:cd18874    1 PEPTVGALIFNPDGKVLLVRSHK--WNDLYGIPGGKVEWGETLEEALKREVKEETGLD--ITDIRFILVQESINSEEFHK 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 446401971  96 tdfTTHYVVLGFRFRVAEEDLILPDEQhDDYRWLTPDALLasnDVHANSRAYFLAE 151
Cdd:cd18874   77 ---PAHFVFVDYLARTDSSEVVLNEEA-VEYLWVEPEEAL---KYPLNSFTRLLLE 125

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: 49.56 E-value: 2.71e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  26 NSRGEFLLGKRTNRPA---QGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPitagQFygVWQHFYDDNFSGTDfTTHY 102
Cdd:cd18882   10 DDRGKVLLQLRDDKPGipyPGYWGLFGGHLEPGETPEEAIRRELEEEIGYEPG----EF--RFFLLYTEDDGEDR-IRHV 82

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 446401971 103 VVlgFRFRVAEEDLILPDEQhdDYRWLTPDALLAS 137
Cdd:cd18882   83 FH--APLDVDLSDLVLNEGQ--ALRLFSPEEILQG 113

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

Pssm-ID: 467576 [Multi-domain] Cd Length: 135 Bit Score: 49.60 E-value: 2.86e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  25 ENSRGEFLLGKRTNRPAQ--GYWFVPGGRVQKDETLEAAFERLTMAELGLRL-PITAGQFYGVWQHFYDDNFSGTDFTTH 101
Cdd:cd04694   10 EDSDDRVLLTRRAKHMRTfpGVWVPPGGHVELGESLLEAGLRELQEETGLEVsDIQSLSLLGLWESVYPTLLSIGLPKRH 89

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 446401971 102 YVVLGFRFRVAEEDLILPDEQH-----DDYRWLTPDALLA 136
Cdd:cd04694   90 HIVVYYLVKLSESHENQEQLKLqedevDAAVWLPKSLLAK 129

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: 49.45 E-value: 4.35e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  10 TVVRSTP-------LVSLDFIaENSRGEFLLGKR--TNRPAQGYW-FVPGGRVQKDET-LEAAfERLTMAELGLRLPITA 78
Cdd:cd04693   16 THRRGEPlpegeyhLVVHVWI-FNSDGEILIQQRspDKKGFPGMWeASTGGSVLAGETsLEAA-IRELKEELGIDLDADE 93

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 446401971  79 GQFYGvWQHFYDDNFsgtDFtthYVvlgFRFRVAEEDLILPDEQHDDYRWLTPDALLA 136
Cdd:cd04693   94 LRPIL-TIRFDNGFD---DI---YL---FRKDVDIEDLTLQKEEVQDVKWVTLEEILE 141

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

Pssm-ID: 467564 [Multi-domain] Cd Length: 135 Bit Score: 48.72 E-value: 6.03e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 446401971  28 RGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLP 75
Cdd:cd04681   16 EGEILFVRRAKEPGKGKLDLPGGFVDPGESAEEALRRELREELGLKIP 63

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

Pssm-ID: 467568 [Multi-domain] Cd Length: 138 Bit Score: 46.80 E-value: 3.68e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  26 NSRGEFLL--GKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITA--GQfygVWQHFYDDNFSGTDFTTH 101
Cdd:cd04685    9 DPDGRVLLfrFHDPDDPGRSWWFTPGGGVEPGESPEQAAVRELREETGLRLEPDDlgGP---VWRRRAVFDFSGETVRQD 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 446401971 102 ---YVVLGFRFRVAEEDLiLPDEQ--HDDYRWLTPDALLASNDV 140
Cdd:cd04685   86 erfFLVRVPAFEVDTAGW-TDLERavIDGHRWWSLAELAATGET 128

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 48.33 E-value: 3.73e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 446401971  26 NSRGEFLLGKRT-NRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDD 91
Cdd:PRK08999  14 DADGRILLARRPeGKHQGGLWEFPGGKVEPGETVEQALARELQEELGIE--VTAARPLITVRHDYPD 78

translation initiation factor IF-2B alpha subunit; Eukaryotic translation initiation factor 2B subunit alpha (EIF2B1) is one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. 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: 467584 [Multi-domain] Cd Length: 129 Bit Score: 46.48 E-value: 4.08e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  27 SRGEFLLGKRTNRPA--QGYWFVPGGRVQKDETLEAAFERLTMAELGLRLP----ITAGQFYgvwqHFYDDnfsgtDFTT 100
Cdd:cd18872    9 HDGKVLLFRRSDKVGtyQGRWAGISGSIESDDPPLAAAWREIREETGLTPEdvelLRQGKPF----EFTDE-----SLGR 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 446401971 101 HYVVLGFRFRVAEEDLILPDEQHDDYRWLTPDALLASNDV 140
Cdd:cd18872   80 EWTVHPFLFRLKDDRAIKLDWEHTEWEWVDPTDILDYETV 119

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: 45.37 E-value: 8.91e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  29 GEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNFSGTdftthYVVlgFR 108
Cdd:cd04691   12 GKVLLVKRAYGPGKGRWTLPGGFVEEGETLDEAIVREVLEETGID--AKPVGIIGVRSGVIRDGKSDN-----YVV--FL 82

                         90       100       110
                 ....*....|....*....|....*....|..
gi 446401971 109 FRVAEEDLILPDEQHDDYRWLTPDALLASNDV 140
Cdd:cd04691   83 LEYVGGEPKPDERENSEAGFLTLEEALANEDI 114

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: 44.16 E-value: 2.53e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  23 IAENSRGEFLLGKRTNRPaqGYW-FVpGGRVQKDETLEAAFERLTMAELGLRLP--ITAGQFYgvwQHFYDDNFSGTDFT 99
Cdd:cd04664    8 YRKDEEGEVLLLKRTDDG--GFWqSV-TGGIEDGETPWQAALRELKEETGLDPLelQLIDLNV---SNFYEIFDDWRPGV 81

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 446401971 100 THYVVLGFRFRVAEEDLILPDEQHDDYRWLTPDALLA 136
Cdd:cd04664   82 TVNTEHVFAVEVPEEQPIRLSPEHTDYRWLPYEEAAE 118

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

Pssm-ID: 467554 [Multi-domain] Cd Length: 131 Bit Score: 43.68 E-value: 3.85e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  26 NSRGEFLLGKRTNRPAQGYWFvPGGRVQKDETLEAAFERLTMAELGLRLpitagQFYGV--WQHFYDDNFSGTDFtthYV 103
Cdd:cd04670   11 NENNEVLVVQEKYGGPGGWKL-PGGLVDPGEDIGEAAVREVFEETGIDT-----EFVSIlgFRHQHPGRFGKSDL---YF 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 446401971 104 VlgFRFRVAEEDLILPDEQH-DDYRWLTPDALLASNDVHANSRA 146
Cdd:cd04670   82 V--CRLRPLSDEEIKICPEEiAEAKWMPLEEYLKQPNVSQINKL 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: 43.68 E-value: 4.68e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  16 PLVSLD---FIAENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAgQFYgvwqhFYDDN 92
Cdd:cd18873    1 PSVTVDcviFGFDDGELKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETGLKDIYLE-QLG-----TFGDP 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 446401971  93 fsGTDFTTHYVVLGFRFRVAEEDLIL-PDEQHDDYRWLTPDALL 135
Cdd:cd18873   75 --DRDPRGRVISVAYLALVPEEDLAPkAGDDAAEARWFPVDELL 116

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

Pssm-ID: 467594 Cd Length: 136 Bit Score: 43.61 E-value: 4.77e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  44 YWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNfsgtdfTTHYVVLGFRFRVAEEDL-----IL 118
Cdd:cd18883   23 KTFLPGGHIEIGESAEIALVRELREELGLS--CKVGRYLGAVENQWQDK------EVIHVELNHLFEVELQDLhtsdtPE 94

                         90       100
                 ....*....|....*....|
gi 446401971 119 PDEQHDDYRWLTPDALLASN 138
Cdd:cd18883   95 SQEPHLEFYWIPYNDLELHN 114

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

Pssm-ID: 467535 [Multi-domain] Cd Length: 126 Bit Score: 42.09 E-value: 1.34e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  23 IAENSRGEFLLGKRTNRPaQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVwQHFyddNFSGTdftthy 102
Cdd:cd03429    7 LVTNGEDKILLARQPRWP-PGRYSLLAGFVEPGETLEEAVRREVKEEVGLR--VKNVRYVGS-QPW---PFPSS------ 73

                         90       100       110
                 ....*....|....*....|....*....|....
gi 446401971 103 VVLGFRFRVAEEDLILPDEQHDDYRWLTPDALLA 136
Cdd:cd03429   74 LMLGFTAEADSGEITVDDDELEDARWFSRDELPE 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.

Pssm-ID: 467534 [Multi-domain] Cd Length: 132 Bit Score: 41.77 E-value: 1.89e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  25 ENSRGEFLLGKRtnrPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpitagqfygvwQHFYDDNFSgtdFTTHYVV 104
Cdd:cd03428   13 DNGEIEFLLLQH---SYGGHWDFPKGHVEPGESELETALRETKEETGLT------------VDDLPPGFR---ETLTYSF 74

                         90       100       110
                 ....*....|....*....|....*....|....
gi 446401971 105 LGFRF--------RVAEEDLILPDEQHDDYRWLT 130
Cdd:cd03428   75 KEGVEktvvyflaELTPDVEVKLSEEHQDYKWLP 108

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

Pssm-ID: 467542 [Multi-domain] Cd Length: 130 Bit Score: 40.70 E-value: 5.19e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  22 FIAENSRGEFLLgkrTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGL---RLPITAGQFYGVWQHFYDDNFSGTDf 98
Cdd:cd03674    7 FVVNPDRGKVLL---VHHRKLGRWLQPGGHVEPDEDPLEAALREAREETGLdveLLSPLSPDPLDIDVHPIPANPGEPA- 82

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 446401971  99 TTHYVVlGFRFRVAEEDLILPDEQHDDYRWLTPDALLA 136
Cdd:cd03674   83 HLHLDV-RYLAVADGDEALRKSDESSDVRWFPLDELEE 119

NUDIX hydrolase subfamily; Nucleoside triphosphatase NudI catalyzes the hydrolysis of nucleoside triphosphates, with a preference for pyrimidine deoxynucleoside triphosphates (dUTP, dTTP and dCTP). It is a members of the NUDIX hydrolase superfamily which 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: 467577 [Multi-domain] Cd Length: 134 Bit Score: 40.30 E-value: 8.97e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  29 GEFLLGKR-TNR---PAQgyWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQfygVWQhFYDDNF-----SGTDFT 99
Cdd:cd04696   13 GCYLLCKMaDDRgvfPGQ--WALSGGGVEPGERIEEALRREIREELGEQLILSDIT---PWT-FRDDIRiktypDGRQEE 86

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 446401971 100 THYVVLGFRFRVAEEDLILPDEqHDDYRWLTPDAlLASNDVHANSR 145
Cdd:cd04696   87 IYMIYLIFDCVSANRDVCINDE-FQDYAWVKPAD-LANYDLNVATR 130

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

Pssm-ID: 467567 [Multi-domain] Cd Length: 140 Bit Score: 39.91 E-value: 1.15e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  23 IAENSRGEFLLGKRTNrpaqGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVW-QHFYddnfsGTDFTTH 101
Cdd:cd04684   21 VIFNDEGKVLLVQTPN----GGYFLPGGGIEPGETPEEALHREVLEETGWE--IEIGEFLGNAsRYFY-----SPDYDRY 89

                         90       100       110
                 ....*....|....*....|....*....|...
gi 446401971 102 YVVLGFrFRVAE--EDLILPDEQHDDYRWLTPD 132
Cdd:cd04684   90 YLNIGY-FYLAElvRKVSEPTEEDHELVWLPPE 121

NUDIX domain;

Pssm-ID: 464330 [Multi-domain] Cd Length: 114 Bit Score: 39.60 E-value: 1.18e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971   22 FIAENSRGEFLLGKRtnrPA----QGYWFVPGGRVQKDETLEAAFERLtmAELGLRLPITAGqfyGVWQHFYddnfsgtd 97
Cdd:pfam14815   3 LVIRNGDGRVLLRKR---PEkgllGGLWEFPGGKVEPGETLEEALARL--EELGIEVEVLEP---GTVKHVF-------- 66

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 446401971   98 ftTHYVVLGFRFRVAEedLILPDEQHDDYRWLTPDAL 134
Cdd:pfam14815  67 --THFRLTLHVYLVRE--VEGEEEPQQELRWVTPEEL 99

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 40.76 E-value: 1.24e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 446401971  29 GEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQFYGVWQHFYDD 91
Cdd:PRK05379 214 GHVLLVRRRAEPGKGLWALPGGFLEQDETLLDACLRELREETGLKLPEPVLRGSIRDQQVFDH 276

nucleoside triphosphatase NudI; Provisional

Pssm-ID: 185369 [Multi-domain] Cd Length: 141 Bit Score: 39.73 E-value: 1.31e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  29 GEFLLGKR-TNR---PAQgyWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAgqfYGVWQhFYDD-----NFSGTDFT 99
Cdd:PRK15472  15 GAYLLCKMaDDRgvfPGQ--WALSGGGVEPGERIEEALRREIREELGEQLLLTE---ITPWT-FRDDirtktYADGRKEE 88

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 446401971 100 THYVVLGFRFRVAEEDLILPDEqHDDYRWLTPDAL 134
Cdd:PRK15472  89 IYMIYLIFDCVSANRDVKINEE-FQDYAWVKPEDL 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: 467588 [Multi-domain] Cd Length: 121 Bit Score: 38.72 E-value: 2.17e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  28 RGEFLLGKRTNRPAqgyWFVPGGRVQKDETLEAAFERLTMAELGLRLPITagqfyGVWQHFYDDNFSGTDFTTHYVVLGF 107
Cdd:cd18876   11 AGRVLLVKPTYKDG---WELPGGVVEAGESPLQAARREVREELGLDVPVG-----RLLAVDWVPPAGGGDDAVLFVFDGG 82

                         90       100
                 ....*....|....*....|....*....
gi 446401971 108 RFRVAEEDLI-LPDEQHDDYRWLTPDALL 135
Cdd:cd18876   83 VLTPEQAAAIrLQDEELSAYRFVTPEEAA 111

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

Pssm-ID: 467555 [Multi-domain] Cd Length: 130 Bit Score: 38.83 E-value: 2.74e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 446401971  26 NSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGL 72
Cdd:cd04671    9 NEQGEVLMIQEAKRSCRGKWYLPAGRVEPGESIVEAAKREVKEETGL 55

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

Pssm-ID: 467563 [Multi-domain] Cd Length: 121 Bit Score: 38.38 E-value: 2.96e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  23 IAENSRGEFLLGKRTNRPAqgyWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAgQFYGVWQHFYddnFSGTDFTTHY 102
Cdd:cd04680    6 IVLDDAGRVLLVRHTYVPG---WYLPGGGVDKGETAEEAARRELREEAGVVLTGPP-RLFGVYFNRR---VSPRDHVALY 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 446401971 103 VVLGFRfrvaEEDLILPDEQHDDYRWLTPDAL 134
Cdd:cd04680   79 RVREFE----QTEPPEPNGEIAEAGFFALDAL 106

NUDIX domain family found in Deinococcus radiodurans, and similar proteins; Deinococcus radiodurans protein DR_0079 is one of 21 NUDIX hydrolases that it encodes, and it has been observed to have a marked preference for cytosine ribonucleoside 5'-diphosphate (CDP) and cytosine ribonucleoside 5'-triphosphate (CTP), and for their corresponding deoxyribose nucleotides, dCDP and dCTP, to a lesser degree. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467602 [Multi-domain] Cd Length: 121 Bit Score: 37.96 E-value: 3.98e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  26 NSRGEFLLGKRTNRPAQ---GYWFVPGGRVQKDETLEAAFERLTMAELGLRLpitAGQFYGVWQHF--YDDNFSGtdFTT 100
Cdd:cd24154   11 NSQGQLWIPRRTADKRIfplALDMSVGGHVSSGETYEQAFVRELQEELNLDL---DQLSYRVLGKLtpYEHGVSA--FMK 85

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 446401971 101 HYvvlgfRFRVAEEdlilPDEQHDD---YRWLTPDALL 135
Cdd:cd24154   86 VY-----EIRSDET----PDYNPDDfseAFWLTPEELL 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: 467545 [Multi-domain] Cd Length: 123 Bit Score: 37.17 E-value: 9.76e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 446401971  29 GEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPItaGQFYGVW 85
Cdd:cd04511   13 GKVLLCRRAIEPRKGYWTLPAGFMELGETTEQGAARETREEAGARVEI--GSLYAVY 67

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

Pssm-ID: 467543 [Multi-domain] Cd Length: 138 Bit Score: 37.12 E-value: 1.08e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  29 GEFLL-------GKRTNRPAqgywfvpgGRVQKDETLEAAFERLTMAELGLRLPITAgqFYGVWQHFYDDNfsGTDFtth 101
Cdd:cd03675   11 GRFLLveeetdgRLVLNQPA--------GHLEPGESLLEAAIRETLEETGWEVEPTA--LLGIYQWTAPDN--GVTY--- 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 446401971 102 yvvlgFRFR-VAEEDLILPDEQHDD----YRWLTPDALLASNDVH 141
Cdd:cd03675   76 -----LRFAfAGELLEHLPDQPLDSgiirAHWLTLEEILALQARL 115

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

Pssm-ID: 467570 [Multi-domain] Cd Length: 130 Bit Score: 35.99 E-value: 2.28e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  42 QGYWFVPGGRVQKDETLEAAFERLTMAELGlrLPITAGQFYGVWQHFYDDNfsGTDFttHYVVLGFRFRVAEEDLILPDE 121
Cdd:cd04688   23 DDYYRLPGGRVEFGETSEDALVREFKEELG--VEVEVVRLLFVVENFFTYD--GKPF--HEIGFYYLVELSDEALYEQDI 96

                         90       100
                 ....*....|....*....|
gi 446401971 122 QHD-------DYRWLTPDAL 134
Cdd:cd04688   97 FFLeedgeklEFRWIPLEEL 116

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: 467565 [Multi-domain] Cd Length: 123 Bit Score: 34.96 E-value: 6.36e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 446401971  43 GYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAgqfyGVWQHFYDDN 92
Cdd:cd04682   28 NLWDLPGGGREGDETPFACVLRELREELGLALPEDR----LVWERVYPSN 73

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

Pssm-ID: 467596 [Multi-domain] Cd Length: 147 Bit Score: 34.90 E-value: 6.52e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  29 GEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLpiTAGQFYGVWqhfyddNFSGTDFTTHYVVLGFR 108
Cdd:cd18886   11 DEVLLLNRNKKPNMGKWNGVGGKLEPGESPEECAIREVFEETGLEL--EDLQLRGIV------TFPSFDGGEDWLMYVFL 82

                         90       100       110
                 ....*....|....*....|....*....|...
gi 446401971 109 FRVAEEDLILPDEQhDDYRWLTPDALLASNDVH 141
Cdd:cd18886   83 AEAFSGELVESDRE-GILAWVPIDWLLNLPLWE 114

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: 34.84 E-value: 7.40e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446401971  25 ENSRGEFLLGKRtnrPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNFSGTDFTTHYvv 104
Cdd:cd03673   12 RGGGGEVLLIHR---PRYDDWSLPKGKLEPGETPEEAAVREVEEETGLR--VRLGRPLGTTRYTYTRKGKGILKKVHY-- 84

                         90       100       110
                 ....*....|....*....|....*....|...
gi 446401971 105 lgFRFRVAEEDLIL-PDEQHDDYRWLTPDALLA 136
Cdd:cd03673   85 --WLMRALGGEFLPqPEEEIDEVRWLPPDEARR 115

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

Pssm-ID: 467553 [Multi-domain] Cd Length: 120 Bit Score: 34.25 E-value: 8.53e-03

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gi 446401971  29 GEFLLGKRTnRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPIT 77
Cdd:cd04669   11 DKLLLIRRT-KPGEEYYVFPGGGIEPGETPEEAALREAVEELGLDVAVT 58