NCBI Conserved Domain Search

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: 242.43 E-value: 2.62e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101   2 EEWDLLNENRELTGKTHIRGEKLAPGELHLVIHVCIFNEKGQLLIQKRQKDKEGWPNYWDLSAAGSALKGETSQQAAERE 81
Cdd:cd04693    1 ELWDLYDENRNKTGRTHRRGEPLPEGEYHLVVHVWIFNSDGEILIQQRSPDKKGFPGMWEASTGGSVLAGETSLEAAIRE 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 497600101  82 VQEELGIMIDLSGTRAKFSYHFEEGFDDYWFITKDVQLSDLTLQKEEVADARFVTKEELEALRSSGEFIPY 152
Cdd:cd04693   81 LKEELGIDLDADELRPILTIRFDNGFDDIYLFRKDVDIEDLTLQKEEVQDVKWVTLEEILEMIESGEFIPY 151

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

Pssm-ID: 441052 [Multi-domain] Cd Length: 162 Bit Score: 153.82 E-value: 2.47e-48

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101   1 MEEWDLLNENRELTGkTHIRGEKLAPGELHLVIHVCIFNEKGQLLIQKRQKDKEGWPNYWDLSAAGSALKGETSQQAAER 80
Cdd:COG1443    1 EELVDLVDEDGRPIG-TAERAEVHRKGLLHRAFSVFVFNSDGRLLLQRRALTKDHWPGLWDNTVCGHPRAGETYEEAAVR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  81 EVQEELGIMIDLSGT-RAKFSYH-------FEEGFDDYWFITKDVqlsDLTLQKEEVADARFVTKEELEALRSSG--EFI 150
Cdd:COG1443   80 ELEEELGITVDDDLRpLGTFRYRavdanglVENEFCHVFVARLDG---PLTPQPEEVAEVRWVTLEELLALLEAGpeAFT 156


                 ...
gi 497600101 151 PYF 153
Cdd:COG1443  157 PWF 159

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

Pssm-ID: 467574 [Multi-domain] Cd Length: 142 Bit Score: 102.25 E-value: 2.13e-28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101   5 DLLNENRELTGKTHiRGEKLAPGELHLVIHVCIFN-EKGQLLIQKRQKDKEGWPNYWDLSAAGSALKGETSQQAAEREVQ 83
Cdd:cd04692    2 DIVDEDGRPIGVAT-RSEVHRQGLWHRTVHVWLVNpEEGRLLLQKRSANKDDFPGLWDISAAGHIDAGETYEEAAVRELE 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 497600101  84 EELGimIDLSGTRAKFSYHFEEGFDDYWFI----------TKDVQLSDLTLQKEEVADARFVT 136
Cdd:cd04692   81 EELG--LTVSPEDLIFLGVIREEVIGGDFIdnefvhvylyETDRPLEEFKLQPEEVAGVVFVD 141

Nudix hydrolase homolog

Pssm-ID: 215425 [Multi-domain] Cd Length: 770 Bit Score: 101.82 E-value: 1.59e-25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101   2 EEWDLLNENRELTGKTHIRGEKLAPGELHLVIHVCIFNEK-GQLLIQKRQKDKEGWPNYWDLSAAGSALKGETSQQAAER 80
Cdd:PLN02791   4 EHLDVLTAAGEKTGVSKPRGEVHRDGDYHRAVHVWIYSEStQELLLQRRADCKDSWPGQWDISSAGHISAGDTSLLSAQR 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  81 EVQEELGIMIDLSGTRAKFSYHFE----------EGFDDYWFIT--KDVQLSDLTLQKEEVADARFVTKEELEAL--RSS 146
Cdd:PLN02791  84 ELEEELGIILPKDAFELLFVFLQEcvindgkfinNEYNDVYLVTtlDPIPLEAFTLQESEVSAVKYMSIEEYKSAlaKED 163


                 ....*.
gi 497600101 147 GEFIPY 152
Cdd:PLN02791 164 PAYVPY 169

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: 93.45 E-value: 9.19e-25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101   5 DLLNENRELTGKThIRGEKLAPGELHLVIHVCIFNEKGQLLIQKRQKDKEGWPNYWDLSAAGSALKGETSQQAAEREVQE 84
Cdd:cd04697    2 DIVDENNEVVGAA-TRAEMRRQKLIHRATYIVVRNAAGRLLVQKRTMDKDYCPGYLDPATGGVVGAGESYEENARRELEE 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 497600101  85 ELGimIDLSGTRAKFSYHFEEGFDDYWFITKDVQLS-DLTLQKEEVADARFVTKEELEALRSSGEFIP 151
Cdd:cd04697   81 ELG--IDGVPLRPLFTFYYEDDRSRVWGALFECVYDgPLKLQPEEVAEVDWMSEDEILQAARGEEFTP 146

Isopentenyl diphosphate isomerase; Isopentenyl diphosphate (IPP) isomerase, a member of the NUDIX hydrolase superfamily, is a key enzyme in the isoprenoid biosynthetic pathway. Isoprenoids comprise a large family of natural products including sterols, carotenoids, dolichols and prenylated proteins. These compounds are synthesized from two precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). IPP isomerase catalyzes the interconversion of IPP and DMAPP by a stereoselective antarafacial transposition of hydrogen. The enzyme requires one Mn2+ or Mg2+ ion in its active site to fold into an active conformation and also contains 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. The metal binding site is present within the active site and plays structural and catalytical roles. IPP isomerase is well represented in several bacteria, archaebacteria and eukaryotes, including fungi, mammals and plants. Despite sequence variations (mainly at the N-terminus), the core structure is highly conserved.

Pssm-ID: 467529 [Multi-domain] Cd Length: 162 Bit Score: 86.01 E-value: 7.45e-22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101   6 LLNENRELTG-----KTHIRGeklapGELHLVIHVCIFNEKGQLLIQKRQKDKEGWPNYWDLSAAGSALKGETSQQAAER 80
Cdd:cd02885    4 LVDEDDNPIGtaeklEAHRKG-----TLLHRAFSVFLFNSKGELLLQRRALSKYTWPGLWTNTCCSHPLPGEGVEDAAQR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  81 EVQEELGIMIDLSGTRAKFSYHFEegFDDYW---------FITKDVqlsDLTLQKEEVADARFVTKEELEAL--RSSGEF 149
Cdd:cd02885   79 RLREELGIPVCDLEELPRFRYRAT--DDNGLveheidhvfVGRADG---DPVPNPEEVSDYRWVSLEELRELlaATPEAF 153


                 ....
gi 497600101 150 IPYF 153
Cdd:cd02885  154 TPWF 157

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: 2.27e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  31 LVIHVCIFNEKGQLLIQKRQKDKegWPNYWDLsAAGSALKGETSQQAAEREVQEELGimIDLSGTRAKFSYHFEEGFDD- 109
Cdd:cd02883    1 VAVGAVVFDDEGRVLLVRRSDGP--GPGGWEL-PGGGVEPGETPEEAAVREVREETG--LDVEVLRLLGVYEFPDPDEGr 75

                         90       100       110
                 ....*....|....*....|....*....|.
gi 497600101 110 ----YWFITKDVQLSDLTLQKEEVADARFVT 136
Cdd:cd02883   76 hvvvLVFLARVVGGEPPPLDDEEISEVRWVP 106

isopentenyl-diphosphate Delta-isomerase;

Pssm-ID: 235156 [Multi-domain] Cd Length: 184 Bit Score: 69.23 E-value: 3.98e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101   6 LLNENRELTGKThirgEKLA----PGELHLVIHVCIFNEKGQLLIQKRQKDKEGWPNYWDLSAAGSALKGETSQQAAERE 81
Cdd:PRK03759  10 LLDEQGVPTGTA----EKAAahtaDTPLHLAFSCYLFDADGRLLVTRRALSKKTWPGVWTNSCCGHPQPGESLEDAVIRR 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  82 VQEELGIMI-DLSGTRAKFSYH-------FEEGFDDYWFITKDvqlSDLTLQKEEVADARFVTKEELEALRSSG--EFIP 151
Cdd:PRK03759  86 CREELGVEItDLELVLPDFRYRatdpngiVENEVCPVFAARVT---SALQPNPDEVMDYQWVDPADLLRAVDATpwAFSP 162


                 ..
gi 497600101 152 YF 153
Cdd:PRK03759 163 WM 164

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: 64.16 E-value: 7.82e-14

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 497600101  32 VIHVCIFNEKGQLLIQKRQKDKEGWPNYWDLSAAGSALKGETSQQAAEREVQEELGIMIDlsgtraKFSYHF 103
Cdd:cd24154    4 VVNAFLINSQGQLWIPRRTADKRIFPLALDMSVGGHVSSGETYEQAFVRELQEELNLDLD------QLSYRV 69

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 64.04 E-value: 1.12e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101   29 LHLVIHVCIFNEKGQLLIQKRQKDKegWPNYWDLsAAGSALKGETSQQAAEREVQEELGIMID----LSGTRAKFSYHFE 104
Cdd:pfam00293   2 RRVAVGVVLLNEKGRVLLVRRSKKP--FPGWWSL-PGGKVEPGETPEEAARRELEEETGLEPEllelLGSLHYLAPFDGR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 497600101  105 EGFDDYWFI--TKDVQLSDLTLQKEEVADARFVTKEELEALR---SSGEFIPYF 153
Cdd:pfam00293  79 FPDEHEILYvfLAEVEGELEPDPDGEVEEVRWVPLEELLLLKlapGDRKLLPWL 132

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 61.92 E-value: 7.38e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  30 HLVIHVCIFNEKGQLLIQKRqkDKEGWPNYWDLsAAGSALKGETSQQAAEREVQEELGIMIDLSGTRAKFSYHFEEGFDD 109
Cdd:COG1051    6 KVAVDAVIFRKDGRVLLVRR--ADEPGKGLWAL-PGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHPDRGHVVS 82

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 497600101 110 YWFITKDvqLSDLTLQKEEVADARFVTKEELEALR 144
Cdd:COG1051   83 VAFLAEV--LSGEPRADDEIDEARWFPLDELPELA 115

NUDIX hydrolase YfcD; Provisional

Pssm-ID: 185291 [Multi-domain] Cd Length: 180 Bit Score: 60.97 E-value: 5.04e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101   2 EEW-DLLNENRELTG---KTHIRGEKLAPGELHLVIHvcifNEKGQLLIQKRQKDKEGWPNYWDLSAAGSALKGETSQQA 77
Cdd:PRK15393   9 TEWvDIVNENNEVIAqasREQMRAQCLRHRATYIVVH----DGMGKILVQRRTETKDFLPGMLDATAGGVVQAGEQLLES 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 497600101  78 AEREVQEELGIMIDLSGTRAKFsYHFEEGFDDYWFITKDVQLSDLTLQKEEVADARFVTKEELEAlrSSGEFIP 151
Cdd:PRK15393  85 ARREAEEELGIAGVPFAEHGQF-YFEDENCRVWGALFSCVSHGPFALQEEEVSEVCWMTPEEITA--RCDEFTP 155

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: 54.06 E-value: 6.75e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  35 VCIFNEKGQLLIQKRqKDKEGW--PnywdlsaAGSALKGETSQQAAEREVQEELGIMID-------LSGtrAKFSYHFEE 105
Cdd:cd04677   17 VIILNEQGRILLQKR-TDTGDWglP-------GGAMELGESLEETARREVFEETGLTVEelellgvYSG--KDLYYTYPN 86

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 497600101 106 GFDDYW----FITKDVQlSDLTLQKEEVADARFVTKEEL 140
Cdd:cd04677   87 GDEVYNvtavYLVRDVS-GELKVDDEESLELRFFSLDEL 124

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: 53.11 E-value: 1.89e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  35 VCIFNEKGQLLIQKRQKDKEGwPNYWDLsAAGSALKGETSQQAAEREVQEELGIMIDLSGTRAKFSYhfeEGFDD---YW 111
Cdd:COG0494   18 VVLLDDDGRVLLVRRYRYGVG-PGLWEF-PGGKIEPGESPEEAALRELREETGLTAEDLELLGELPS---PGYTDekvHV 92

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 497600101 112 FITKDV-QLSDLTLQKE-EVADARFVTKEELEALRSSGEF 149
Cdd:COG0494   93 FLARGLgPGEEVGLDDEdEFIEVRWVPLDEALALVTAGEI 132

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: 50.28 E-value: 1.55e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  34 HVCIFNEKGQLLIQKrqkdkegwPNY---WDLsAAGSALKGETSQQAAEREVQEELGIMIDLS------------GTRAK 98
Cdd:cd18876    4 GALFTDAAGRVLLVK--------PTYkdgWEL-PGGVVEAGESPLQAARREVREELGLDVPVGrllavdwvppagGGDDA 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 497600101  99 FSYHFEEGFDDywfitkDVQLSDLTLQKEEVADARFVTKEELEAL 143
Cdd:cd18876   75 VLFVFDGGVLT------PEQAAAIRLQDEELSAYRFVTPEEAAEL 113

thiamine diphosphokinase Tnr3 from Schizosaccharomyces pombe and similar proteins; Tnr3 is a bifunctional enzyme composed of a C-terminal thiamine pyrophosphokinase domain, which transfers pyrophosphate from ATP to thiamine and an N-terminal NUDIX hydrolase domain that converts oxidized derivatives of thiamine diphosphate (oxothiamine and oxythiamine) to their respective monophosphates. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belong to this superfamily requires a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467544 Cd Length: 153 Bit Score: 50.19 E-value: 2.66e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  40 EKGQLLIQKRQKDKEGWPNYWDLSAAGSALKGETSQQAAEREVQEELGIMIDLSGTRAKF----SYHFEegfDDYWFITK 115
Cdd:cd03676   19 DGLRLWVARRSATKATYPGKLDNLVAGGVPAGESPLETLVREAEEEAGLPEDLARQARPAagrvSYFYR---SDEGGLQP 95

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 497600101 116 DVQ-LSDLTL--------QKEEVADARFVTKEE-LEALRsSGEFIP 151
Cdd:cd03676   96 EVLyVYDLELpedfvpkpQDGEVESFELMSVDEvLEALR-AGEFKP 140

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 51.41 E-value: 3.65e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 497600101  32 VIHVC---IFNEKGQLLIQKRQKDKEgWPNYWDLSAaGSALKGETSQQAAEREVQEELGIMID 91
Cdd:PRK08999   4 RIHVAagvIRDADGRILLARRPEGKH-QGGLWEFPG-GKVEPGETVEQALARELQEELGIEVT 64

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: 48.41 E-value: 8.25e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  37 IFNEKGQLLIQKRQkDKEG--WPNYWDLSaaGSAL-KGETSQQAAEREVQEELGimIDLSGTRAKFSYHFEEGFDD---Y 110
Cdd:cd18882    8 LYDDRGKVLLQLRD-DKPGipYPGYWGLF--GGHLePGETPEEAIRRELEEEIG--YEPGEFRFFLLYTEDDGEDRirhV 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 497600101 111 WFITKDVQLSDLTLQkeEVADARFVTKEELEALRSSGEFIP 151
Cdd:cd18882   83 FHAPLDVDLSDLVLN--EGQALRLFSPEEILQGPLYSNLAG 121

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: 48.40 E-value: 1.02e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  31 LVIhVCIFNEKGQLLIQKRQKDkegwPNYWDlSAAGSALKGETSQQAAEREVQEELGIMIDLSGTRAKFSYHFEEGFDD- 109
Cdd:cd04664    4 LVV-IYRKDEEGEVLLLKRTDD----GGFWQ-SVTGGIEDGETPWQAALRELKEETGLDPLELQLIDLNVSNFYEIFDDw 77

                         90       100
                 ....*....|....*....|....*.
gi 497600101 110 ---------YWFI-----TKDVQLSD 121
Cdd:cd04664   78 rpgvtvnteHVFAvevpeEQPIRLSP 103

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: 47.87 E-value: 1.41e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  32 VIhVCIFNEKGQLLIqKRQKdkeGWP-NYWDLSAaGSALKGETSQQAAEREVQEELGIMIDlsgtraKFSYHFeegfDDY 110
Cdd:cd03429    4 VI-VLVTNGEDKILL-ARQP---RWPpGRYSLLA-GFVEPGETLEEAVRREVKEEVGLRVK------NVRYVG----SQP 67

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 497600101 111 W---------FITkDVQLSDLTLQKEEVADARFVTKEELEAL 143
Cdd:cd03429   68 WpfpsslmlgFTA-EADSGEITVDDDELEDARWFSRDELPEA 108

isopentenyl-diphosphate delta-isomerase

Pssm-ID: 215303 [Multi-domain] Cd Length: 247 Bit Score: 48.58 E-value: 2.53e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  22 EKLAP-GELHLVIHVCIFNEKGQLLIQKRQKDKEGWPNYWDLSAAGSALKGETSQQ-----------------AAEREVQ 83
Cdd:PLN02552  47 EKIEPrGLLHRAFSVFLFNSKYELLLQQRAATKVTFPLVWTNTCCSHPLYGQDPNEvdreselidgnvlgvknAAQRKLL 126

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  84 EELGIMIDLSGTrAKFSY----------HFEEGFDDYW---------FITKDvqlSDLTLQ--KEEVADARFVTKEELEA 142
Cdd:PLN02552 127 HELGIPAEDVPV-DQFTFltrlhykaadDVTHGPDGKWgeheldyllFIRPV---RDVKVNpnPDEVADVKYVNREELKE 202

                        170
                 ....*....|....
gi 497600101 143 L--RSSG-EFIPYF 153
Cdd:PLN02552 203 MmrKESGlKLSPWF 216

dihydroneopterin triphosphate pyrophosphatase; Provisional

Pssm-ID: 236516 [Multi-domain] Cd Length: 148 Bit Score: 47.58 E-value: 2.65e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 497600101  35 VCIFNEKGQLLIQKRQKDkegwPNYWDlSAAGSALKGETSQQAAEREVQEELGIMIDLSGT 95
Cdd:PRK09438  12 VVIYTPDLGVLMLQRADD----PDFWQ-SVTGSLEEGETPAQTAIREVKEETGIDVLAEQL 67

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: 45.99 E-value: 7.77e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  36 CIFNEKGQ-LLIQKRQKDKEGW--PnywdlsaAGSALKGETSQQAAEREVQEELGIM---IDLSGTRAKFSYHFeeGFDD 109
Cdd:cd04670    8 LVINENNEvLVVQEKYGGPGGWklP-------GGLVDPGEDIGEAAVREVFEETGIDtefVSILGFRHQHPGRF--GKSD 78

                         90       100       110
                 ....*....|....*....|....*....|...
gi 497600101 110 YWFITKDVQLSD--LTLQKEEVADARFVTKEEL 140
Cdd:cd04670   79 LYFVCRLRPLSDeeIKICPEEIAEAKWMPLEEY 111

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

Pssm-ID: 467564 [Multi-domain] Cd Length: 135 Bit Score: 46.02 E-value: 8.54e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  35 VCIFNEkGQLLIQKRQKDkegwP--NYWDLsAAGSALKGETSQQAAEREVQEELGIMIDlsgtRAKF------SYHFeEG 106
Cdd:cd04681   11 VIIRNE-GEILFVRRAKE----PgkGKLDL-PGGFVDPGESAEEALRRELREELGLKIP----KLRYlcslpnTYLY-KG 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 497600101 107 FD----DYWFITKDVQLSDLTLQKEEVADARFVTKEELE----ALRS 145
Cdd:cd04681   80 ITyktcDLFFTAELDEKPKLKKAEDEVAELEWLDLEEIEpeklAFPS 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: 467566 [Multi-domain] Cd Length: 137 Bit Score: 45.67 E-value: 1.00e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 497600101  33 IHVCIFNEkGQLLIQKRQKDkeGWPNYWDLSAAGSALKGETSQQAAEREVQEELGIMID 91
Cdd:cd04683    3 VHLLLVRG-DEVLLLRRANT--GYDDGWWHLPAGHVEAGETVRAAAVREAKEELGVEID 58

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: 45.24 E-value: 1.28e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  44 LLIQKRQKDKegwpnyWDLsAAGSALKGETSQQAAEREVQEELGIMIDLSGTRAKFSYHFEEGFDD-----YWFITKDVQ 118
Cdd:cd03673   19 LLIHRPRYDD------WSL-PKGKLEPGETPEEAAVREVEEETGLRVRLGRPLGTTRYTYTRKGKGilkkvHYWLMRALG 91

                         90       100
                 ....*....|....*....|....*
gi 497600101 119 LSDLTLQKEEVADARFVTKEELEAL 143
Cdd:cd03673   92 GEFLPQPEEEIDEVRWLPPDEARRL 116

DR1025 and similar proteins; DR1025 from Deinococcus radiodurans, a member of the NUDIX hydrolase superfamily, show nucleoside triphosphatase and dinucleoside polyphosphate pyrophosphatase activities. Like other enzymes belonging to this superfamily, it requires a divalent cation, in this case Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. In general, 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: 467580 [Multi-domain] Cd Length: 147 Bit Score: 44.52 E-value: 3.04e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  16 KTHIRGEKLAPGelhlvihVCIFNEKGQ-LLIQKR----QKDKEGwpnYWDLSAaGSALKGETSQQAAEREVQEELGIMI 90
Cdd:cd04700    6 RTHVPVTLRAAG-------VVLLNERGDiLLVQEKgisgHPEKAG---LWHIPS-GAVEDGENPQDAAVREACEETGLRV 74

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 497600101  91 DLsgtrAKFSYHFEEGFDDYWFITKDVQLSDLTLQK-------EEVADARFVTKEELEALRSSGE 148
Cdd:cd04700   75 RL----VKFLGAYLGRFPDGVLVLRHVWLAEPEPGQvlapaftDEIAEASFVSREEFAQLYAAGQ 135

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: 43.98 E-value: 3.46e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  33 IHVC---IFNEkGQLLIQKRQKDKEgWPNYWDLsAAGSALKGETSQQAAEREVQEELGIMIDLSGtrakfsyHFEEGFDD 109
Cdd:cd03425    1 IEVVaaiIVDD-GRVLIAQRPEGKH-LAGLWEF-PGGKVEPGETPEQALVRELREELGIEVEVGE-------PLGTVEHD 70

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 497600101 110 YWF--ITKDVQLSDL---TLQKEEVADARFVTKEELEAL 143
Cdd:cd03425   71 YPDfhVRLHVYLCTLwsgEPQLLEHQELRWVTPEELDDL 109

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: 43.83 E-value: 3.48e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  71 GETSQQAAEREVQEELGIMIDLSGTRAKFSYHFEEGFDDYW--FITKDVQlSDLTLQKEEVADARFVTKEELEALRSSGE 148
Cdd:cd04691   38 GETLDEAIVREVLEETGIDAKPVGIIGVRSGVIRDGKSDNYvvFLLEYVG-GEPKPDERENSEAGFLTLEEALANEDIAD 116


                 ....*
gi 497600101 149 FIPYF 153
Cdd:cd04691  117 MSREL 121

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: 43.55 E-value: 7.55e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  37 IFNEKGQLLIQKrqkdKEGWPnYWDLSAAGSALkGETSQQAAEREVQEELGI------MIDLSGTRAkFSYHFEEGFDDY 110
Cdd:cd04676   24 ILNEDGRILLQR----KGGLG-LWSLPAGAIEP-GEHPAEAVIREVREETGLlvkptrLLGVFGGKE-FRYTYPNGDQVE 96

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 497600101 111 W--FITKDVQLSD-LTLQKEEVADARFVTKEELEAL 143
Cdd:cd04676   97 YtvIAFKCVVTGGtLNAIDGETSELRYFSRTQMPTL 132

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: 42.55 E-value: 1.58e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 497600101  35 VCIFNEKGQLLIQKRQKDKEGW--PNywdlsaaGSALKGETSQQAAEREVQEELGI 88
Cdd:cd03671    8 IVLFNRDGQVLVGRRIDVPGAWqfPQ-------GGIDEGEDPEEAALRELYEETGL 56

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: 41.51 E-value: 2.85e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  42 GQLLIQKRQkDKEG--WPNYWDLSAaGSALKGETSQQAAEREVQEELGimIDLSGTRAKFSYHFEEGFDDY---WFITKd 116
Cdd:cd04682   11 DKLLTILRD-DKPGipFPNLWDLPG-GGREGDETPFACVLRELREELG--LALPEDRLVWERVYPSNHNPGrqsWFFVA- 85

                         90
                 ....*....|....*...
gi 497600101 117 vqlsdlTLQKEEVADARF 134
Cdd:cd04682   86 ------RLPADEVDAIRF 97

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: 41.84 E-value: 3.19e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 497600101  33 IHVCIFNEKGQLLIQKRQKDkegwP--NYWdLSAAGSALKGETSQQAAEREVQEELGIMIDLSGtrAKFSYHFEEGFDD 109
Cdd:cd03430   18 IDLIIRNEDGEILLGKRNNR----PaqGYW-FVPGGRILKNETLDDAFKRIAREELGLEVTINA--AEFLGVYEHFYDD 89

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: 40.23 E-value: 8.27e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  44 LLIQKRQkdkegwPNYWDLSAaGSALKGETSQQAAEREVQEELGIMIDL--SGTRAKFSYHFEEGFDD---YWF----IT 114
Cdd:cd03428   20 LLLQHSY------GGHWDFPK-GHVEPGESELETALRETKEETGLTVDDlpPGFRETLTYSFKEGVEKtvvYFLaeltPD 92

                         90       100
                 ....*....|....*....|....*
gi 497600101 115 KDVQLSdltlqkEEVADARFVTKEE 139
Cdd:cd03428   93 VEVKLS------EEHQDYKWLPYEE 111

GDP-mannose mannosyl hydrolase;

Pssm-ID: 237966 [Multi-domain] Cd Length: 159 Bit Score: 40.51 E-value: 1.11e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  39 NEKGQLLIQKR-QKDKEGwpnYWdLSAAGSALKGETSQQAAEREVQEELGIMIDLS-GTRAKFSYHF-EEGFDDYWFITK 115
Cdd:PRK15434  26 NSRGEFLLGKRtNRPAQG---YW-FVPGGRVQKDETLEAAFERLTMAELGLRLPITaGQFYGVWQHFyDDNFSGTDFTTH 101

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 497600101 116 --------DVQLSDLTLQKEEVADARFVTKEELEA 142
Cdd:PRK15434 102 yvvlgfrlRVAEEDLLLPDEQHDDYRWLTPDALLA 136

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: 38.81 E-value: 2.98e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  35 VCIFNEKGQLLIQKRQKDKEGWPNYWDLSAaGSALKGETSQQAAEREVQEELGIMIDLSGT-------RAKFSYHFEEGF 107
Cdd:cd04694    7 VLIEDSDDRVLLTRRAKHMRTFPGVWVPPG-GHVELGESLLEAGLRELQEETGLEVSDIQSlsllglwESVYPTLLSIGL 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 497600101 108 DDYWFIT--------KDVQLS-DLTLQKEEVADARFVTKEELEAL 143
Cdd:cd04694   86 PKRHHIVvyylvklsESHENQeQLKLQEDEVDAAVWLPKSLLAKL 130

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: 467595 [Multi-domain] Cd Length: 125 Bit Score: 38.55 E-value: 3.68e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  55 GWPNYWDLSAAGSALKGETSQQAAEREVQEELGimidLSGTRAKFSYHFEEGFDDYWFITKDVQLSDLTLQKEEVADARF 134
Cdd:cd18884   29 AWPEGWYGLVTGFLEAGESPEEAVLREVKEELG----LDGHEAKFIGHYAFPERNQLIIAYHVRARGNVKLNEELDDYKI 104


                 ....*.
gi 497600101 135 VTKEEL 140
Cdd:cd18884  105 VPIDKL 110

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

Pssm-ID: 467552 [Multi-domain] Cd Length: 117 Bit Score: 38.42 E-value: 3.71e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 497600101  66 GSALKGETSQQAAEREVQEELGimidLSGTRAKFSYHFEEGF 107
Cdd:cd04667   28 GKIEPGESPLEAAIRELKEETG----LAALSLLYLFEHEGPH 65

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

Pssm-ID: 467572 [Multi-domain] Cd Length: 123 Bit Score: 36.74 E-value: 1.33e-03

                         10        20
                 ....*....|....*....|.
gi 497600101  71 GETSQQAAEREVQEELGIMID 91
Cdd:cd04690   35 GETPLQALVRELKEELGLDLD 55

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: 36.90 E-value: 1.36e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 497600101  42 GQLLIQKRQKDKEGwpNYWDLsAAGSALKGETSQQAAEREVQEELGIMIDLSG 94
Cdd:cd04679   13 GRLLLVLRLRAPEA--GHWGL-PGGKVDWLETVEDAVRREILEELGLEIELTR 62

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: 36.76 E-value: 1.42e-03

                         10
                 ....*....|....*...
gi 497600101  71 GETSQQAAEREVQEELGI 88
Cdd:cd04688   36 GETSEDALVREFKEELGV 53

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: 36.45 E-value: 1.79e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  37 IFNEkGQLLIQKRQKDKegwPNYWDLsAAGSALKGETSQQAAEREVQEELGIMIDLSGTRAKFSYHFEEgfDDYWFI--- 113
Cdd:cd04699    9 IFDN-GRVLLLRRSRAG---AGEWEL-PGGRLEPGESPEEALKREVKEETGLDVSVGELLDTWTFELDP--DKGVFIvty 81

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 497600101 114 -----TKDVQLSDltlqkeEVADARFVTKEELEALR 144
Cdd:cd04699   82 lcrlvGGEVTLSD------EHEEYEWVTPEELAELE 111

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

Pssm-ID: 182536 [Multi-domain] Cd Length: 135 Bit Score: 36.64 E-value: 1.88e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 497600101  32 VIHV--CIFNEKGQLLIQKRQKDKEGwPNYWDLsAAGSALKGETSQQAAEREVQEELGI 88
Cdd:PRK10546   3 MIDVvaAIIERDGKILLAQRPAHSDQ-AGLWEF-AGGKVEPGESQPQALIRELREELGI 59

Adp-ribose pyrophosphatase (ADPRase) found in Thermus thermophilus, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) such as found in extreme thermophile Thermus thermophilus (TtADPRase) catalyzes the hydrolysis of ADPR to AMP and ribose 5'-phosphate in the presence of Mg2+ and Zn2+ ions. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

Pssm-ID: 467608 [Multi-domain] Cd Length: 151 Bit Score: 36.33 E-value: 2.99e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  65 AGSALKGETSQQAAEREVQEELGIMIDLSgtrAKFSYHFEEGFDD---YWFITKDVQLSDLTLQKEEVADARFVTKEE-L 140
Cdd:cd24160   53 AGLIDPGETPEEAARRELAEETGLSGDLT---YLTRFYVSPGFCDeklHVFLAENLREVEAHPDEDEAIEVVWMRPEEvL 129


                 ....*...
gi 497600101 141 EALRSSGE 148
Cdd:cd24160  130 ERLRRGEV 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: 467563 [Multi-domain] Cd Length: 121 Bit Score: 35.69 E-value: 3.14e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497600101  37 IFNEKGQ-LLIqkRQKDKEGW--PnywdlsaAGSALKGETSQQAAEREVQEELGimIDLSGTRAKFSYHFEEGF--DDY- 110
Cdd:cd04680    7 VLDDAGRvLLV--RHTYVPGWylP-------GGGVDKGETAEEAARRELREEAG--VVLTGPPRLFGVYFNRRVspRDHv 75

                         90       100
                 ....*....|....*....|....*
gi 497600101 111 -WFITKDVQLSDLTLQKEEVADARF 134
Cdd:cd04680   76 aLYRVREFEQTEPPEPNGEIAEAGF 100

ADP-ribose pyrophosphatase, UDP-glucose pyrophosphatase, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) ( NUDIX (Nucleoside diphosphate-linked moiety X)) motif 5; Nudt5) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

Pssm-ID: 467530 [Multi-domain] Cd Length: 134 Bit Score: 35.56 E-value: 3.74e-03

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gi 497600101  70 KGETSQQAAEREVQEELGI----MIDLsgtrakFSYHFEEGFDD---YWFITKDVQLSDLTLQKE-EVADARFVTKEELE 141
Cdd:cd03424   40 PGEDPEEAARRELEEETGYtagdLELL------GSFYPSPGFSDeriHLFLAEDLTPVSEQALDEdEFIEVVLVPLEEAL 113


                 ....*....
gi 497600101 142 ALRSSGEFI 150
Cdd:cd03424  114 EMIEDGEIT 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: 467586 [Multi-domain] Cd Length: 125 Bit Score: 34.95 E-value: 5.79e-03

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gi 497600101  37 IFNEKGQLLIQKRQKdkegWPNYWDLSAaGSALKGETSQQAAEREVQEELGIMI 90
Cdd:cd18874    9 IFNPDGKVLLVRSHK----WNDLYGIPG-GKVEWGETLEEALKREVKEETGLDI 57

nucleoside triphosphatase NudI; Provisional

Pssm-ID: 185369 [Multi-domain] Cd Length: 141 Bit Score: 35.11 E-value: 7.66e-03

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 497600101  35 VC-IFNEKGQLLIQKRQKDKEGWPNYWDLSAAGSAlKGETSQQAAEREVQEELG 87
Cdd:PRK15472   7 VCpLIQNDGAYLLCKMADDRGVFPGQWALSGGGVE-PGERIEEALRREIREELG 59