NCBI Conserved Domain Search

GDP-mannose mannosyl hydrolase;

Pssm-ID: 237966 [Multi-domain] Cd Length: 159 Bit Score: 333.26 E-value: 2.39e-119

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799   1 MFLRQEDFATVVRSTPLVSLDFIVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQ 80
Cdd:PRK15434    1 MFLRQEDFATVVRSTPLISLDFIVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQ 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1114288799  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: 256.40 E-value: 3.36e-89

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799   3 LRQEDFATVVRSTPLVSLDFIVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQFY 82
Cdd:cd03430     1 LPEEDFKTVVENTPLVSIDLIIRNEDGEILLGKRNNRPAQGYWFVPGGRILKNETLDDAFKRIAREELGLEVTINAAEFL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1114288799  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: 85.42 E-value: 3.95e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  14 STPLVSLDFIVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYddnf 93
Cdd:COG1051     3 KVPKVAVDAVIFRKDGRVLLVRRADEPGKGLWALPGGKVEPGETPEEAALRELREETGLE--VEVLELLGVFDHPD---- 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1114288799  94 sgtdfTTHYVVLGFRFRVAEEDLILPDEqHDDYRWLTPDALLA 136
Cdd:COG1051    77 -----RGHVVSVAFLAEVLSGEPRADDE-IDEARWFPLDELPE 113

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 83.30 E-value: 3.73e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITagQFYGVWQHFYDDNFSGTDftTHY 102
Cdd:pfam00293   9 VLLNEKGRVLLVRRSKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELL--ELLGSLHYLAPFDGRFPD--EHE 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1114288799 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: 72.05 E-value: 4.18e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNfsgtdfTTHY 102
Cdd:cd02883     6 VVFDDEGRVLLVRRSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLD--VEVLRLLGVYEFPDPDE------GRHV 77

                          90       100
                  ....*....|....*....|....*....
gi 1114288799 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: 6.89e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  29 GEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNFSGTDFttHYVVLGFR 108
Cdd:cd04673    12 GRVLLVRRGNPPDAGLWSFPGGKVELGETLEDAALRELREETGLE--AEVVGLLTVVDVIERDEAGRVRF--HYVILDFL 87

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1114288799 109 FRVAEEDLILPDEQhDDYRWLTPDALLASNDV 140
Cdd:cd04673    88 AEWVSGEPVAGDDA-LDARWFSLEELDGLPLT 118

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: 59.50 E-value: 4.66e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQ-HFYDDNFsgtdfttH 101
Cdd:cd04678     8 IVLNDDGKVLLGRRKGSHGAGTWALPGGHLEFGESFEECAAREVLEETGLE--IRNVRFLTVTNdVFEEEGK-------H 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1114288799 102 YVVLGFRFRVAEEDL--ILPDEQHDDYRWLTPDALLASNDVHANSRAYF 148
Cdd:cd04678    79 YVTIFVLAEVDDGEPeeNMEPDKCEGWEWFSWDELPPLRPLFLPLANLL 127

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: 5.66e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  29 GEFLLGKRtNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDnfsgtdfTTHYVVLGFR 108
Cdd:cd04699    13 GRVLLLRR-SRAGAGEWELPGGRLEPGESPEEALKREVKEETGLD--VSVGELLDTWTFELDP-------DKGVFIVTYL 82

                          90       100
                  ....*....|....*....|....*.
gi 1114288799 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: 2.28e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPAQ-GYWFVPGGRVQKDETLEAAFERLTMAELGLRLpitagqfyGVWQHFYD-DNFSGTDFTT 100
Cdd:COG0494    19 VLLDDDGRVLLVRRYRYGVGpGLWEFPGGKIEPGESPEEAALRELREETGLTA--------EDLELLGElPSPGYTDEKV 90

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1114288799 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: 3.78e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  28 RGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNfsgtdfTTHYVVLGF 107
Cdd:cd04679    12 DGRLLLVLRLRAPEAGHWGLPGGKVDWLETVEDAVRREILEELGLE--IELTRLLCVVDQIDAAD------GEHWVAPVY 83

                          90       100
                  ....*....|....*....|....*...
gi 1114288799 108 RFRVAE-EDLILPDEQHDDYRWLTPDAL 134
Cdd:cd04679    84 LAEIFSgEPRLMEPEKHGGIGWFALDAL 111

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: 5.75e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSrGEFLLGKRT-NRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNfsgtdfttH 101
Cdd:cd03425     7 IIVDD-GRVLIAQRPeGKHLAGLWEFPGGKVEPGETPEQALVRELREELGIE--VEVGEPLGTVEHDYPDF--------H 75

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1114288799 102 YVVLGFRFRVAEEDLILPDeqHDDYRWLTPDALLA 136
Cdd:cd03425    76 VRLHVYLCTLWSGEPQLLE--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: 51.90 E-value: 3.28e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  16 PLVSLDFIVENSRGEFLLGKRTNrpAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNFSG 95
Cdd:cd18874     1 PEPTVGALIFNPDGKVLLVRSHK--WNDLYGIPGGKVEWGETLEEALKREVKEETGLD--ITDIRFILVQESINSEEFHK 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1114288799  96 tdfTTHYVVLGFRFRVAEEDLILPDEQhDDYRWLTPDALLasnDVHANSRAYFLAE 151
Cdd:cd18874    77 ---PAHFVFVDYLARTDSSEVVLNEEA-VEYLWVEPEEAL---KYPLNSFTRLLLE 125

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: 51.14 E-value: 7.98e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPAQ--GYWFVPGGRVQKDETLEAAFERLTMAELGLRL-PITAGQFYGVWQHFYDDNFSGTDFT 99
Cdd:cd04694     8 LIEDSDDRVLLTRRAKHMRTfpGVWVPPGGHVELGESLLEAGLRELQEETGLEVsDIQSLSLLGLWESVYPTLLSIGLPK 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1114288799 100 THYVVLGFRFRVAEEDLILPDEQH-----DDYRWLTPDALLA 136
Cdd:cd04694    88 RHHIVVYYLVKLSESHENQEQLKLqedevDAAVWLPKSLLAK 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: 50.99 E-value: 1.34e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKR--TNRPAQGYW-FVPGGRVQKDET-LEAAfERLTMAELGLRLPITAGQFYGvWQHFYDDNFsgtDF 98
Cdd:cd04693    35 WIFNSDGEILIQQRspDKKGFPGMWeASTGGSVLAGETsLEAA-IRELKEELGIDLDADELRPIL-TIRFDNGFD---DI 109

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1114288799  99 tthYVvlgFRFRVAEEDLILPDEQHDDYRWLTPDALLA 136
Cdd:cd04693   110 ---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: 50.26 E-value: 1.84e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1114288799  23 IVENsRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLP 75
Cdd:cd04681    12 IIRN-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: 467593 [Multi-domain] Cd Length: 130 Bit Score: 49.56 E-value: 2.76e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  26 NSRGEFLLGKRTNRPA---QGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPitagQFygVWQHFYDDNFSGTDfTTHY 102
Cdd:cd18882    10 DDRGKVLLQLRDDKPGipyPGYWGLFGGHLEPGETPEEAIRRELEEEIGYEPG----EF--RFFLLYTEDDGEDR-IRHV 82

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1114288799 103 VVlgFRFRVAEEDLILPDEQhdDYRWLTPDALLAS 137
Cdd:cd18882    83 FH--APLDVDLSDLVLNEGQ--ALRLFSPEEILQG 113

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: 47.57 E-value: 1.99e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLL--GKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITA--GQfygVWQHFYDDNFSGTDF 98
Cdd:cd04685     6 LLLDPDGRVLLfrFHDPDDPGRSWWFTPGGGVEPGESPEQAAVRELREETGLRLEPDDlgGP---VWRRRAVFDFSGETV 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1114288799  99 TTH---YVVLGFRFRVAEEDLiLPDEQ--HDDYRWLTPDALLASNDV 140
Cdd:cd04685    83 RQDerfFLVRVPAFEVDTAGW-TDLERavIDGHRWWSLAELAATGET 128

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 49.10 E-value: 2.02e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRT-NRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDD 91
Cdd:PRK08999   11 VIRDADGRILLARRPeGKHQGGLWEFPGGKVEPGETVEQALARELQEELGIE--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: 4.43e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  27 SRGEFLLGKRTNRPA--QGYWFVPGGRVQKDETLEAAFERLTMAELGLRLP----ITAGQFYgvwqHFYDDnfsgtDFTT 100
Cdd:cd18872     9 HDGKVLLFRRSDKVGtyQGRWAGISGSIESDDPPLAAAWREIREETGLTPEdvelLRQGKPF----EFTDE-----SLGR 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1114288799 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: 9.87e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  29 GEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNFSGTdftthYVVlgFR 108
Cdd:cd04691    12 GKVLLVKRAYGPGKGRWTLPGGFVEEGETLDEAIVREVLEETGID--AKPVGIIGVRSGVIRDGKSDN-----YVV--FL 82

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1114288799 109 FRVAEEDLILPDEQHDDYRWLTPDALLASNDV 140
Cdd:cd04691    83 LEYVGGEPKPDERENSEAGFLTLEEALANEDI 114

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

Pssm-ID: 467554 [Multi-domain] Cd Length: 131 Bit Score: 45.22 E-value: 1.05e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPAQGYWFvPGGRVQKDETLEAAFERLTMAELGLRLpitagQFYGV--WQHFYDDNFSGTDFtt 100
Cdd:cd04670     8 LVINENNEVLVVQEKYGGPGGWKL-PGGLVDPGEDIGEAAVREVFEETGIDT-----EFVSIlgFRHQHPGRFGKSDL-- 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1114288799 101 hYVVlgFRFRVAEEDLILPDEQH-DDYRWLTPDALLASNDVHANSRA 146
Cdd:cd04670    80 -YFV--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: 44.84 E-value: 1.43e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  16 PLVSLD---FIVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAgQFYgvwqhFYDDN 92
Cdd:cd18873     1 PSVTVDcviFGFDDGELKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETGLKDIYLE-QLG-----TFGDP 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1114288799  93 fsGTDFTTHYVVLGFRFRVAEEDLIL-PDEQHDDYRWLTPDALL 135
Cdd:cd18873    75 --DRDPRGRVISVAYLALVPEEDLAPkAGDDAAEARWFPVDELL 116

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: 44.79 E-value: 1.49e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPaQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVwQHFyddNFSGTdftthy 102
Cdd:cd03429     7 LVTNGEDKILLARQPRWP-PGRYSLLAGFVEPGETLEEAVRREVKEEVGLR--VKNVRYVGS-QPW---PFPSS------ 73

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1114288799 103 VVLGFRFRVAEEDLILPDEQHDDYRWLTPDALLA 136
Cdd:cd03429    74 LMLGFTAEADSGEITVDDDELEDARWFSRDELPE 107

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: 44.56 E-value: 1.92e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  22 FIVENSRGEFLLgkrTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGL---RLPITAGQFYGVWQHFYDDNFSGTDf 98
Cdd:cd03674     7 FVVNPDRGKVLL---VHHRKLGRWLQPGGHVEPDEDPLEAALREAREETGLdveLLSPLSPDPLDIDVHPIPANPGEPA- 82

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1114288799  99 TTHYVVlGFRFRVAEEDLILPDEQHDDYRWLTPDALLA 136
Cdd:cd03674    83 HLHLDV-RYLAVADGDEALRKSDESSDVRWFPLDELEE 119

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: 43.78 E-value: 3.76e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPaqGYW-FVpGGRVQKDETLEAAFERLTMAELGLRLP--ITAGQFYgvwQHFYDDNFSGTDFT 99
Cdd:cd04664     8 YRKDEEGEVLLLKRTDDG--GFWqSV-TGGIEDGETPWQAALRELKEETGLDPLelQLIDLNV---SNFYEIFDDWRPGV 81

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1114288799 100 THYVVLGFRFRVAEEDLILPDEQHDDYRWLTPDALLA 136
Cdd:cd04664    82 TVNTEHVFAVEVPEEQPIRLSPEHTDYRWLPYEEAAE 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: 467594 Cd Length: 136 Bit Score: 43.61 E-value: 5.02e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  44 YWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNfsgtdfTTHYVVLGFRFRVAEEDL-----IL 118
Cdd:cd18883    23 KTFLPGGHIEIGESAEIALVRELREELGLS--CKVGRYLGAVENQWQDK------EVIHVELNHLFEVELQDLhtsdtPE 94

                          90       100
                  ....*....|....*....|
gi 1114288799 119 PDEQHDDYRWLTPDALLASN 138
Cdd:cd18883    95 SQEPHLEFYWIPYNDLELHN 114

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: 43.31 E-value: 6.63e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  22 FIVENSRGEFLLGKRtnrPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpitagqfygvwQHFYDDNFSgtdFTTH 101
Cdd:cd03428    10 YRRDNGEIEFLLLQH---SYGGHWDFPKGHVEPGESELETALRETKEETGLT------------VDDLPPGFR---ETLT 71

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1114288799 102 YVVLGFRF--------RVAEEDLILPDEQHDDYRWLT 130
Cdd:cd03428    72 YSFKEGVEktvvyflaELTPDVEVKLSEEHQDYKWLP 108

NUDIX domain;

Pssm-ID: 464330 [Multi-domain] Cd Length: 114 Bit Score: 41.53 E-value: 2.22e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  22 FIVENSRGEFLLGKRtnrPA----QGYWFVPGGRVQKDETLEAAFERLtmAELGLRLPITAGqfyGVWQHFYddnfsgtd 97
Cdd:pfam14815   3 LVIRNGDGRVLLRKR---PEkgllGGLWEFPGGKVEPGETLEEALARL--EELGIEVEVLEP---GTVKHVF-------- 66

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1114288799  98 ftTHYVVLGFRFRVAEedLILPDEQHDDYRWLTPDAL 134
Cdd:pfam14815  67 --THFRLTLHVYLVRE--VEGEEEPQQELRWVTPEEL 99

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: 41.46 E-value: 2.84e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSrGEFLLGKR-TNRPA-QGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQfygVWQhFYDDNF-----SG 95
Cdd:cd04696     8 LIENE-GCYLLCKMaDDRGVfPGQWALSGGGVEPGERIEEALRREIREELGEQLILSDIT---PWT-FRDDIRiktypDG 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1114288799  96 TDFTTHYVVLGFRFRVAEEDLILPDEqHDDYRWLTPDAlLASNDVHANSR 145
Cdd:cd04696    83 RQEEIYMIYLIFDCVSANRDVCINDE-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: 40.68 E-value: 5.75e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNrpaqGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVW-QHFYddnfsGTDFTTH 101
Cdd:cd04684    21 VIFNDEGKVLLVQTPN----GGYFLPGGGIEPGETPEEALHREVLEETGWE--IEIGEFLGNAsRYFY-----SPDYDRY 89

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1114288799 102 YVVLGFrFRVAE--EDLILPDEQHDDYRWLTPD 132
Cdd:cd04684    90 YLNIGY-FYLAElvRKVSEPTEEDHELVWLPPE 121

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: 40.37 E-value: 7.57e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGL 72
Cdd:cd04671     6 VIINEQGEVLMIQEAKRSCRGKWYLPAGRVEPGESIVEAAKREVKEETGL 55

nucleoside triphosphatase NudI; Provisional

Pssm-ID: 185369 [Multi-domain] Cd Length: 141 Bit Score: 40.12 E-value: 8.87e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSrGEFLLGKR-TNR---PAQgyWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAgqfYGVWQhFYDD-----NF 93
Cdd:PRK15472   10 LIQND-GAYLLCKMaDDRgvfPGQ--WALSGGGVEPGERIEEALRREIREELGEQLLLTE---ITPWT-FRDDirtktYA 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1114288799  94 SGTDFTTHYVVLGFRFRVAEEDLILPDEqHDDYRWLTPDAL 134
Cdd:PRK15472   83 DGRKEEIYMIYLIFDCVSANRDVKINEE-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: 467563 [Multi-domain] Cd Length: 121 Bit Score: 39.54 E-value: 1.05e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPAqgyWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAgQFYGVWQHFYddnFSGTDFTTHY 102
Cdd:cd04680     6 IVLDDAGRVLLVRHTYVPG---WYLPGGGVDKGETAEEAARRELREEAGVVLTGPP-RLFGVYFNRR---VSPRDHVALY 78

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1114288799 103 VVLGFRfrvaEEDLILPDEQHDDYRWLTPDAL 134
Cdd:cd04680    79 RVREFE----QTEPPEPNGEIAEAGFFALDAL 106

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 40.76 E-value: 1.20e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1114288799  29 GEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQFYGVWQHFYDD 91
Cdd:PRK05379  214 GHVLLVRRRAEPGKGLWALPGGFLEQDETLLDACLRELREETGLKLPEPVLRGSIRDQQVFDH 276

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: 39.49 E-value: 1.32e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPAqgyWFVPGGRVQKDETLEAAFERLTMAELGLRLPITagqfyGVWQHFYDDNFSGTDFTTHY 102
Cdd:cd18876     6 LFTDAAGRVLLVKPTYKDG---WELPGGVVEAGESPLQAARREVREELGLDVPVG-----RLLAVDWVPPAGGGDDAVLF 77

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1114288799 103 VVLGFRFRVAEEDLI-LPDEQHDDYRWLTPDALL 135
Cdd:cd18876    78 VFDGGVLTPEQAAAIrLQDEELSAYRFVTPEEAA 111

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: 39.12 E-value: 1.78e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  22 FIVeNSRGEFLLGKRTNRPAQ---GYWFVPGGRVQKDETLEAAFERLTMAELGLRLpitAGQFYGVWQHF--YDDNFSGt 96
Cdd:cd24154     8 FLI-NSQGQLWIPRRTADKRIfplALDMSVGGHVSSGETYEQAFVRELQEELNLDL---DQLSYRVLGKLtpYEHGVSA- 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1114288799  97 dFTTHYvvlgfRFRVAEEdlilPDEQHDD---YRWLTPDALL 135
Cdd:cd24154    83 -FMKVY-----EIRSDET----PDYNPDDfseAFWLTPEELL 114

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: 37.50 E-value: 8.39e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSrGEFLL-------GKRTNRPAqgywfvpgGRVQKDETLEAAFERLTMAELGLRLPITAgqFYGVWQHFYDDNfsG 95
Cdd:cd03675     6 VVERD-GRFLLveeetdgRLVLNQPA--------GHLEPGESLLEAAIRETLEETGWEVEPTA--LLGIYQWTAPDN--G 72

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1114288799  96 TDFtthyvvlgFRFR-VAEEDLILPDEQHDD----YRWLTPDALLASNDVH 141
Cdd:cd03675    73 VTY--------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: 467560 [Multi-domain] Cd Length: 137 Bit Score: 37.49 E-value: 8.62e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNrpaQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVwqhfyddnFSGTDFTTHY 102
Cdd:cd04677    18 IILNEQGRILLQKRTD---TGDWGLPGGAMELGESLEETARREVFEETGLT--VEELELLGV--------YSGKDLYYTY 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1114288799 103 --------VVLGFRFRVAEEDLILPDEQHDDYRWLTPDAL 134
Cdd:cd04677    85 pngdevynVTAVYLVRDVSGELKVDDEESLELRFFSLDEL 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: 467545 [Multi-domain] Cd Length: 123 Bit Score: 37.17 E-value: 9.56e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1114288799  29 GEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPItaGQFYGVW 85
Cdd:cd04511    13 GKVLLCRRAIEPRKGYWTLPAGFMELGETTEQGAARETREEAGARVEI--GSLYAVY 67

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

Pssm-ID: 467578 [Multi-domain] Cd Length: 157 Bit Score: 37.21 E-value: 1.17e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNR----PaqGYW-FVPGGRVQKDETLEAAFERLTMAELGlrlpITAGQFYGVWQHFYDDNfsgtd 97
Cdd:cd04697    32 VVRNAAGRLLVQKRTMDkdycP--GYLdPATGGVVGAGESYEENARRELEEELG----IDGVPLRPLFTFYYEDD----- 100

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1114288799  98 fttHYVVLG--FRFRVAEEdLILPDEQHDDYRWLTPDALLA 136
Cdd:cd04697   101 ---RSRVWGalFECVYDGP-LKLQPEEVAEVDWMSEDEILQ 137

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

Pssm-ID: 467570 [Multi-domain] Cd Length: 130 Bit Score: 35.99 E-value: 2.47e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  42 QGYWFVPGGRVQKDETLEAAFERLTMAELGlrLPITAGQFYGVWQHFYDDNfsGTDFttHYVVLGFRFRVAEEDLILPDE 121
Cdd:cd04688    23 DDYYRLPGGRVEFGETSEDALVREFKEELG--VEVEVVRLLFVVENFFTYD--GKPF--HEIGFYYLVELSDEALYEQDI 96

                          90       100
                  ....*....|....*....|
gi 1114288799 122 QHD-------DYRWLTPDAL 134
Cdd:cd04688    97 FFLeedgeklEFRWIPLEEL 116

8-oxo-dGTP diphosphatase MutT;

Pssm-ID: 182721 [Multi-domain] Cd Length: 129 Bit Score: 36.12 E-value: 2.51e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1114288799  23 IVENSRGEFLLgkrTNRPAQ----GYWFVPGGRVQKDETLEAAFERLTMAELGL 72
Cdd:PRK10776   10 IIRNPNNEIFI---TRRAADahmaGKWEFPGGKIEAGETPEQALIRELQEEVGI 60

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

Pssm-ID: 182536 [Multi-domain] Cd Length: 135 Bit Score: 35.87 E-value: 3.29e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENsRGEFLLGKRTNRPAQ-GYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHfyddNFSGTDFTTH 101
Cdd:PRK10546   10 IIER-DGKILLAQRPAHSDQaGLWEFAGGKVEPGESQPQALIRELREELGIE--ATVGEYVASHQR----EVSGRRIHLH 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1114288799 102 yvvlgfRFRVAEEDLILPDEQHDDYRWLTP-DAL---LASNDV 140
Cdd:PRK10546   83 ------AWHVPDFHGELQAHEHQALVWCTPeEALrypLAPADI 119

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

Pssm-ID: 467565 [Multi-domain] Cd Length: 123 Bit Score: 34.96 E-value: 6.18e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1114288799  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: 6.78e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  22 FIVENsrGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLpiTAGQFYGVWqhfyddNFSGTDFTTH 101
Cdd:cd18886     6 FIIRD--DEVLLLNRNKKPNMGKWNGVGGKLEPGESPEECAIREVFEETGLEL--EDLQLRGIV------TFPSFDGGED 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1114288799 102 YVVLGFRFRVAEEDLILPDEQhDDYRWLTPDALLASNDVH 141
Cdd:cd18886    76 WLMYVFLAEAFSGELVESDRE-GILAWVPIDWLLNLPLWE 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: 467587 [Multi-domain] Cd Length: 144 Bit Score: 34.85 E-value: 6.82e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  23 IVENSRGEFLLGKRTNRPAQGYWFvPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNfsgtdftTHY 102
Cdd:cd18875     8 MIYDGEDRVLVLDRVKKDWGGYTF-PGGHVEPGESFVDSVIREVKEETGLT--IKNPELCGIKQWINPDG-------ERY 77


                  ....*.
gi 1114288799 103 VVLGFR 108
Cdd:cd18875    78 IVFLYK 83

diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 and similar proteins; Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 (DIPP2), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 4; Nudt4, and other proteins including DIPP1/Nudt3, DIPP3a;APS2/Nudt10 and DIPP3beta;APS1/Nudt11. DIPP regulates the turnover of diphosphoinositol polyphosphates. The turnover of these high-energy diphosphoinositol polyphosphates represents a molecular switching activity with important regulatory consequences. Molecular switching by diphosphoinositol polyphosphates may contribute to regulating intracellular trafficking. Several alternatively spliced transcript variants have been described, but the full-length nature of some variants has not been determined. Isoforms DIPP2alpha and DIPP2beta are distinguishable from each other solely by DIPP2beta possessing one additional amino acid due to intron boundary skidding in alternate splicing. 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: 467551 [Multi-domain] Cd Length: 128 Bit Score: 34.81 E-value: 7.63e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  22 FIVENSRGEFLL--GKRTNRpaqgyWFVPGGRVQKDETLEAAFERLTMAELGLRlPITAGQFYGVWQhfYDDNFSGTDFT 99
Cdd:cd04666     8 YRITKGELEVLLitSRKTGR-----WILPKGGPEKGETPAEAAAREAWEEAGVR-GKVLKRPLGVYR--YRKRLKGRGLP 79

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1114288799 100 THYVVlgFRFRVAEEdliLPD--EQHDDYR-WLTPD 132
Cdd:cd04666    80 CRVHV--FPLEVTEE---LDDwpEKHERKRrWFSPE 110

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: 34.45 E-value: 8.49e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1114288799  25 ENSRGEFLLGKRtnrPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRlpITAGQFYGVWQHFYDDNFSGTDFTTHYvv 104
Cdd:cd03673    12 RGGGGEVLLIHR---PRYDDWSLPKGKLEPGETPEEAAVREVEEETGLR--VRLGRPLGTTRYTYTRKGKGILKKVHY-- 84

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1114288799 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: 8.96e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1114288799  29 GEFLLGKRTnRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPIT 77
Cdd:cd04669    11 DKLLLIRRT-KPGEEYYVFPGGGIEPGETPEEAALREAVEELGLDVAVT 58