NCBI Conserved Domain Search

GDP-mannose mannosyl hydrolase;

Pssm-ID: 237966 [Multi-domain] Cd Length: 159 Bit Score: 338.65 E-value: 1.41e-121

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043   1 MFLSQEDFATVVRSTPLISIDLIVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMAEGQ 80
Cdd:PRK15434    1 MFLRQEDFATVVRSTPLISLDFIVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQ 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1452262043  81 FYGVWQHFYDDNFSGTGFSTHYIVLGFRLKVSEADLRLPDSQHDDYRWQTPEALLASDNVHDNSRAYFLADRQSGVPGL 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: 257.56 E-value: 1.02e-89

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043   3 LSQEDFATVVRSTPLISIDLIVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMAEGQFY 82
Cdd:cd03430     1 LPEEDFKTVVENTPLVSIDLIIRNEDGEILLGKRNNRPAQGYWFVPGGRILKNETLDDAFKRIAREELGLEVTINAAEFL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1452262043  83 GVWQHFYDDNFSGTGFSTHYIVLGFRLKVSEADLRLPDSQHDDYRWQTPEALLASDNVHDNSRAYF 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: 81.95 E-value: 8.26e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  14 STPLISIDLIVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLpmAEGQFYGVWQHFYDdnf 93
Cdd:COG1051     3 KVPKVAVDAVIFRKDGRVLLVRRADEPGKGLWALPGGKVEPGETPEEAALRELREETGLEV--EVLELLGVFDHPDR--- 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1452262043  94 sgtgfsTHYIVLGFRLKVSEADLRlPDSQHDDYRWQTPEALLA 136
Cdd:COG1051    78 ------GHVVSVAFLAEVLSGEPR-ADDEIDEARWFPLDELPE 113

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 81.38 E-value: 2.22e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  15 TPLISIDLIVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMaeGQFYGVWQHFYDDNFS 94
Cdd:pfam00293   1 KRRVAVGVVLLNEKGRVLLVRRSKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPEL--LELLGSLHYLAPFDGR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1452262043  95 GTgfSTHYIVLGFRLKVSEADLRLPDSQHDDYRWQTPEALLASDNVHDNSRAY 147
Cdd:pfam00293  79 FP--DEHEILYVFLAEVEGELEPDPDGEVEEVRWVPLEELLLLKLAPGDRKLL 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: 67.82 E-value: 1.87e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  23 IVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLpmAEGQFYGVWQHFYDDNfsgtgfSTHY 102
Cdd:cd02883     6 VVFDDEGRVLLVRRSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDV--EVLRLLGVYEFPDPDE------GRHV 77

                          90       100
                  ....*....|....*....|....*..
gi 1452262043 103 IVLGFRLKV-SEADLRLPDSQHDDYRW 128
Cdd:cd02883    78 VVLVFLARVvGGEPPPLDDEEISEVRW 104

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: 53.45 E-value: 9.26e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  23 IVENERGEFLLGKRtNRPAQGF---WFVPGGRVQKDETLSDAFERLTLAELGLQLPMAEG-QFYGVWQHFYDDNFSGTGF 98
Cdd:cd04694     8 LIEDSDDRVLLTRR-AKHMRTFpgvWVPPGGHVELGESLLEAGLRELQEETGLEVSDIQSlSLLGLWESVYPTLLSIGLP 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1452262043  99 STHYIVLGFRLKVSE-----ADLRLPDSQHDDYRWQTPEALLASDNVHD 142
Cdd:cd04694    87 KRHHIVVYYLVKLSEshenqEQLKLQEDEVDAAVWLPKSLLAKLLEAED 135

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: 52.18 E-value: 3.04e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  16 PLISIDLIVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPmaEGQFYGVWQ-HFYDDNFs 94
Cdd:cd04678     1 PRVGVGVIVLNDDGKVLLGRRKGSHGAGTWALPGGHLEFGESFEECAAREVLEETGLEIR--NVRFLTVTNdVFEEEGK- 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1452262043  95 gtgfstHYIVLGFRLKVSEADLR--LPDSQHDDYRWQTPEALLASDNVHDNSRAYF 148
Cdd:cd04678    78 ------HYVTIFVLAEVDDGEPEenMEPDKCEGWEWFSWDELPPLRPLFLPLANLL 127

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: 51.36 E-value: 5.08e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  29 GEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQlpmAE-GQFYGVWQHFYDDNFSGTGFstHYIVLGF 107
Cdd:cd04673    12 GRVLLVRRGNPPDAGLWSFPGGKVELGETLEDAALRELREETGLE---AEvVGLLTVVDVIERDEAGRVRF--HYVILDF 86

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1452262043 108 RLKVSEADLRLPDsqhD--DYRWQTPEALLASD 138
Cdd:cd04673    87 LAEWVSGEPVAGD---DalDARWFSLEELDGLP 116

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

Pssm-ID: 467575 [Multi-domain] Cd Length: 157 Bit Score: 51.76 E-value: 6.31e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  10 TVVRSTPL------ISIDLIVENERGEFLLGKR--TNRPAQGFW-FVPGGRVQKDETLSDAFERLTLAELGLQLPMAEGQ 80
Cdd:cd04693    16 THRRGEPLpegeyhLVVHVWIFNSDGEILIQQRspDKKGFPGMWeASTGGSVLAGETSLEAAIRELKEELGIDLDADELR 95

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1452262043  81 FYGvWQHFYDdnfsgtGFSTHYIvlgFRLKVSEADLRLPDSQHDDYRWQTPEALLA 136
Cdd:cd04693    96 PIL-TIRFDN------GFDDIYL---FRKDVDIEDLTLQKEEVQDVKWVTLEEILE 141

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: 49.99 E-value: 1.45e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  23 IVENErGEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLqlpmaEGQFYGVW--QHFYDDNfsgtGFST 100
Cdd:cd04691     7 VVVKE-GKVLLVKRAYGPGKGRWTLPGGFVEEGETLDEAIVREVLEETGI-----DAKPVGIIgvRSGVIRD----GKSD 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1452262043 101 HYIVlgFRLKVSEADLRLPDSQHDDYRWQTPEALLASDNVHDNSRA 146
Cdd:cd04691    77 NYVV--FLLEYVGGEPKPDERENSEAGFLTLEEALANEDIADMSRE 120

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: 1.45e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1452262043  23 IVENErGEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLP 75
Cdd:cd04681    12 IIRNE-GEILFVRRAKEPGKGKLDLPGGFVDPGESAEEALRRELREELGLKIP 63

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

Pssm-ID: 467579 [Multi-domain] Cd Length: 118 Bit Score: 49.93 E-value: 1.63e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  18 ISIDLIVENErGEFLLGKRtNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQlpMAEGQFYGVWQHFYDdnfsgtg 97
Cdd:cd04699     3 VSVKGVIFDN-GRVLLLRR-SRAGAGEWELPGGRLEPGESPEEALKREVKEETGLD--VSVGELLDTWTFELD------- 71

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1452262043  98 fSTHYIV-LGFRLKVSEADLRLPDsQHDDYRWQTPEAL 134
Cdd:cd04699    72 -PDKGVFiVTYLCRLVGGEVTLSD-EHEEYEWVTPEEL 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: 49.65 E-value: 3.27e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  22 LIVENERGEFLLGKRTNRPAQ-GFWFVPGGRVQKDETLSDAFERLTLAELGLQLpmaegqfyGVWQHFYDdnFSGTGFST 100
Cdd:COG0494    18 VVLLDDDGRVLLVRRYRYGVGpGLWEFPGGKIEPGESPEEAALRELREETGLTA--------EDLELLGE--LPSPGYTD 87

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1452262043 101 ---HYIVLGFRLKVSEADLRLPDsQHDDYRWQTPEALLA 136
Cdd:COG0494    88 ekvHVFLARGLGPGEEVGLDDED-EFIEVRWVPLDEALA 125

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: 47.83 E-value: 1.00e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  23 IVENErGEFLLGKRT-NRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLpmAEGQFYGVWQHFYDDNfsgtgfstH 101
Cdd:cd03425     7 IIVDD-GRVLIAQRPeGKHLAGLWEFPGGKVEPGETPEQALVRELREELGIEV--EVGEPLGTVEHDYPDF--------H 75

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1452262043 102 YIVLGFRLKVSEADLRLPDsqHDDYRWQTPEALLASD 138
Cdd:cd03425    76 VRLHVYLCTLWSGEPQLLE--HQELRWVTPEELDDLD 110

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: 47.15 E-value: 2.32e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  16 PLISIDLIV---ENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMAEgQFY 82
Cdd:cd18873     1 PSVTVDCVIfgfDDGELKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETGLKDIYLE-QLG 69

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: 46.09 E-value: 6.35e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  22 LIVENERGEFLLGKRTNRPaqGFW-FVpGGRVQKDETLSDAFERLTLAELGLQLpmaEGQFYGVWQH--FYDDNFSGTGF 98
Cdd:cd04664     7 IYRKDEEGEVLLLKRTDDG--GFWqSV-TGGIEDGETPWQAALRELKEETGLDP---LELQLIDLNVsnFYEIFDDWRPG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1452262043  99 STHYIVLGFRLKVSE-ADLRLpDSQHDDYRWQTPE---ALLASDNvhdNSRAY 147
Cdd:cd04664    81 VTVNTEHVFAVEVPEeQPIRL-SPEHTDYRWLPYEeaaELLFWPS---NREAL 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: 467586 [Multi-domain] Cd Length: 125 Bit Score: 45.35 E-value: 9.48e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  16 PLISIDLIVENERGEFLLGKRTNrpAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLpmAEGQFYGVWQHFYDDNFSG 95
Cdd:cd18874     1 PEPTVGALIFNPDGKVLLVRSHK--WNDLYGIPGGKVEWGETLEEALKREVKEETGLDI--TDIRFILVQESINSEEFHK 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1452262043  96 TGfstHYIVLGFRLKVSEADLRLPDsQHDDYRWQTPEALL 135
Cdd:cd18874    77 PA---HFVFVDYLARTDSSEVVLNE-EAVEYLWVEPEEAL 112

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: 1.04e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  23 IVENERGEFLLGKRTNRPAqGFWFVPGGRVQKDETLSDAFERLTLAELGLQlpmAEgqFYGV--WQHFYDDNFsgtGFST 100
Cdd:cd04670     8 LVINENNEVLVVQEKYGGP-GGWKLPGGLVDPGEDIGEAAVREVFEETGID---TE--FVSIlgFRHQHPGRF---GKSD 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1452262043 101 HYIVlgFRLK-VSEADLRLPDSQHDDYRWQTPEALLASDNVHDNSRA 146
Cdd:cd04670    79 LYFV--CRLRpLSDEEIKICPEEIAEAKWMPLEEYLKQPNVSQINKL 123

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: 44.17 E-value: 2.54e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  26 NERGEFLLGKRTNRPA---QGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPmaEGQFYGVWQhfyddnFSGTGFSTHY 102
Cdd:cd18882    10 DDRGKVLLQLRDDKPGipyPGYWGLFGGHLEPGETPEEAIRRELEEEIGYEPG--EFRFFLLYT------EDDGEDRIRH 81

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1452262043 103 IVLGfRLKVSEADLRLPDSQhdDYRWQTPEALLASD 138
Cdd:cd18882    82 VFHA-PLDVDLSDLVLNEGQ--ALRLFSPEEILQGP 114

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

Pssm-ID: 467562 [Multi-domain] Cd Length: 126 Bit Score: 44.22 E-value: 2.88e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  28 RGEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMaeGQFYGVWQHFYDDNfsgtgfSTHYIVLGF 107
Cdd:cd04679    12 DGRLLLVLRLRAPEAGHWGLPGGKVDWLETVEDAVRREILEELGLEIEL--TRLLCVVDQIDAAD------GEHWVAPVY 83

                          90       100
                  ....*....|....*....|....*....
gi 1452262043 108 RLKV--SEADLRLPDsQHDDYRWQTPEAL 134
Cdd:cd04679    84 LAEIfsGEPRLMEPE-KHGGIGWFALDAL 111

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

Pssm-ID: 467555 [Multi-domain] Cd Length: 130 Bit Score: 43.45 E-value: 5.82e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1452262043  23 IVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQL 74
Cdd:cd04671     6 VIINEQGEVLMIQEAKRSCRGKWYLPAGRVEPGESIVEAAKREVKEETGLKC 57

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: 42.57 E-value: 9.32e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  22 LIVENERGEFLLGKRTNRPaqgFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMaeGQFYGVwqhFYDDNFSGTGFSTH 101
Cdd:cd18876     5 ALFTDAAGRVLLVKPTYKD---GWELPGGVVEAGESPLQAARREVREELGLDVPV--GRLLAV---DWVPPAGGGDDAVL 76

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1452262043 102 YIVLGFRLKVSEAD-LRLPDSQHDDYRWQTPEALL 135
Cdd:cd18876    77 FVFDGGVLTPEQAAaIRLQDEELSAYRFVTPEEAA 111

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 43.71 E-value: 1.45e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1452262043  23 IVENERGEFLLGKRT-NRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQ 73
Cdd:PRK08999   11 VIRDADGRILLARRPeGKHQGGLWEFPGGKVEPGETVEQALARELQEELGIE 62

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 42.30 E-value: 4.18e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1452262043  29 GEFLLGKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMAEGQFYGVWQHFYDD 91
Cdd:PRK05379  214 GHVLLVRRRAEPGKGLWALPGGFLEQDETLLDACLRELREETGLKLPEPVLRGSIRDQQVFDH 276

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

Pssm-ID: 467577 [Multi-domain] Cd Length: 134 Bit Score: 40.30 E-value: 7.64e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  23 IVENErGEFLLGKR-TNR---PAQgfWFVPGGRVQKDETLSDAFERLTLAELGLQLPMAEGQfygVWQhFYDDNF----- 93
Cdd:cd04696     8 LIENE-GCYLLCKMaDDRgvfPGQ--WALSGGGVEPGERIEEALRREIREELGEQLILSDIT---PWT-FRDDIRiktyp 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1452262043  94 SGTGFSTHYIVLGFRLKVSEADLRLPDsQHDDYRWQTPEAL 134
Cdd:cd04696    81 DGRQEEIYMIYLIFDCVSANRDVCIND-EFQDYAWVKPADL 120

NUDIX domain;

Pssm-ID: 464330 [Multi-domain] Cd Length: 114 Bit Score: 39.60 E-value: 9.80e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  22 LIVENERGEFLLGKRtnrPA----QGFWFVPGGRVQKDETLSDAFERltLAELGLQLPMAEGqfyGVWQHFYddnfsgtg 97
Cdd:pfam14815   3 LVIRNGDGRVLLRKR---PEkgllGGLWEFPGGKVEPGETLEEALAR--LEELGIEVEVLEP---GTVKHVF-------- 66

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1452262043  98 fsTHYIVlgfRLKVSEA-DLRLPDSQHDDYRWQTPEAL 134
Cdd:pfam14815  67 --THFRL---TLHVYLVrEVEGEEEPQQELRWVTPEEL 99

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: 467559 [Multi-domain] Cd Length: 144 Bit Score: 38.92 E-value: 2.41e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  19 SIDLIVENERGEFLLGKRTNrpaQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMAegQFYGVwqhfyddnFSGTGF 98
Cdd:cd04676    19 SVAAVILNEDGRILLQRKGG---LGLWSLPAGAIEPGEHPAEAVIREVREETGLLVKPT--RLLGV--------FGGKEF 85

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1452262043  99 --------STHYIVLGFRLKVSEADLRLPDSQHDDYRW 128
Cdd:cd04676    86 rytypngdQVEYTVIAFKCVVTGGTLNAIDGETSELRY 123

plant diadenosine tetraphosphate (Ap4A) hydrolase and similar proteins; Diadenosine tetraphosphate (Ap4A) hydrolase is a member of the NUDIX hydrolase superfamily. Members of this family are well represented in a variety of prokaryotic and eukaryotic organisms. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one group (represented by this subfamily) and fungi/animals/archaea enzymes 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 the inhibition of such invasive bacteria. Besides the signature NUDIX motif (G[X5]E[X7]REUXEEXGU where U is Ile, Leu, or Val), Ap4A hydrolase is structurally similar to the other members of the NUDIX hydrolase superfamily with some degree of variations. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies.

Pssm-ID: 467539 [Multi-domain] Cd Length: 147 Bit Score: 37.93 E-value: 6.19e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  22 LIVENERGEFLLGKRTNRPaqGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMAE--GQfYGVWqHFYD--DNFSGTG 97
Cdd:cd03671     8 IVLFNRDGQVLVGRRIDVP--GAWQFPQGGIDEGEDPEEAALRELYEETGLSPEDVEiiAE-TPDW-LTYDlpEDLIRKG 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1452262043  98 FSTHYI-----VLGFRLKVSEADLRLPDSQH---DDYRWQTPEALL 135
Cdd:cd03671    84 WGGKYRgqkqkWFLFRFTGDDSEINLDTHEHpefDAWRWVDLEELP 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: 467568 [Multi-domain] Cd Length: 138 Bit Score: 37.55 E-value: 6.79e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  22 LIVENERGEFLL--GKRTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMAE--GQfygVWQHFYDDNFSGTG 97
Cdd:cd04685     5 VLLLDPDGRVLLfrFHDPDDPGRSWWFTPGGGVEPGESPEQAAVRELREETGLRLEPDDlgGP---VWRRRAVFDFSGET 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1452262043  98 FSTH---YIVLGFRLKVSEADL-RLPDSQHDDYRWQTPEALLASD 138
Cdd:cd04685    82 VRQDerfFLVRVPAFEVDTAGWtDLERAVIDGHRWWSLAELAATG 126

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

Pssm-ID: 467560 [Multi-domain] Cd Length: 137 Bit Score: 36.72 E-value: 1.73e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1452262043  23 IVENERGEFLLGKRTNrpaQGFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMAE--GQFYGVWQHFYDDN 92
Cdd:cd04677    18 IILNEQGRILLQKRTD---TGDWGLPGGAMELGESLEETARREVFEETGLTVEELEllGVYSGKDLYYTYPN 86

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: 36.08 E-value: 2.18e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  22 LIVENERGEFLLgkrTNRPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQ---LPMAEGQFYGVWQHFYDDNFsgtGF 98
Cdd:cd03674     7 FVVNPDRGKVLL---VHHRKLGRWLQPGGHVEPDEDPLEAALREAREETGLDvelLSPLSPDPLDIDVHPIPANP---GE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1452262043  99 STHY-IVLGFRLKVSEADLRLPDSQHDDYRWQTPEAlLASDNVHDNSRA 146
Cdd:cd03674    81 PAHLhLDVRYLAVADGDEALRKSDESSDVRWFPLDE-LEELSMDPNLRK 128

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: 35.99 E-value: 2.70e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  25 ENERGEFLLGKRtnrPAQGFWFVPGGRVQKDETLSDAFERLTLAELGLQlpmaegqfygvwQHFYDDNFSgtgFSTHYIV 104
Cdd:cd03428    13 DNGEIEFLLLQH---SYGGHWDFPKGHVEPGESELETALRETKEETGLT------------VDDLPPGFR---ETLTYSF 74

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1452262043 105 LGFRLKV---------SEADLRLpDSQHDDYRWQTPE 132
Cdd:cd03428    75 KEGVEKTvvyflaeltPDVEVKL-SEEHQDYKWLPYE 110

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: 35.27 E-value: 3.78e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  20 IDLIVENERGEFLLGKRTNRPAQ---GFWFVPGGRVQKDETLSDAFERLTLAELGLQLPMAEGQFYGvwqHF--YDDNFS 94
Cdd:cd24154     5 VNAFLINSQGQLWIPRRTADKRIfplALDMSVGGHVSSGETYEQAFVRELQEELNLDLDQLSYRVLG---KLtpYEHGVS 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1452262043  95 gtGFSTHYIvlgfrLKVSEAdlrlPDSQHDD---YRWQTPEALL 135
Cdd:cd24154    82 --AFMKVYE-----IRSDET----PDYNPDDfseAFWLTPEELL 114

nucleoside triphosphatase NudI; Provisional

Pssm-ID: 185369 [Multi-domain] Cd Length: 141 Bit Score: 35.88 E-value: 3.82e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1452262043  23 IVENErGEFLLGKR-TNR---PAQgfWFVPGGRVQKDETLSDAFERLTLAELGLQLPMAEgqfYGVWQhFYDD-----NF 93
Cdd:PRK15472   10 LIQND-GAYLLCKMaDDRgvfPGQ--WALSGGGVEPGERIEEALRREIREELGEQLLLTE---ITPWT-FRDDirtktYA 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1452262043  94 SGTGFSTHYIVLGFRLKVSEADLRLPDsQHDDYRWQTPEAL 134
Cdd:PRK15472   83 DGRKEEIYMIYLIFDCVSANRDVKINE-EFQDYAWVKPEDL 122

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

Pssm-ID: 467591 [Multi-domain] Cd Length: 126 Bit Score: 34.81 E-value: 6.62e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1452262043  22 LIVENERgeFLLGKrtNRPAQG-FWFVPGGRVQKDETLSDAFERLTLAELGL 72
Cdd:cd18880     7 IIIEDGK--LLLVK--HRDEGGiFYILPGGGQEHGETLPEALKRECLEETGL 54