NCBI Conserved Domain Search

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 459.72 E-value: 2.23e-164

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   1 MKRIHVAAAVIRGPESSVLIAKRPLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQV 80
Cdd:PRK08999   2 MKRIHVAAGVIRDADGRILLARRPEGKHQGGLWEFPGGKVEPGETVEQALARELQEELGIEVTAARPLITVRHDYPDKRV 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  81 LLDVWEVLAFAGEPHGAEGQPLAWVAPEELVDYSFPAANRPIVTAARLPQHYLITPDGL-AMPRLLEGIARALDGGIRLI 159
Cdd:PRK08999  82 RLDVRRVTAWQGEPHGREGQPLAWVAPDELAVYPFPPANQPIVRALRLPDTYLITPEGEdGDAAFLARLERALAAGIRLI 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385 160 QLRAPSLPPADYRALAERVMALCAG-RAQLMLKGPLEWVEDFPGAGWHLTAEQLRRAgSGRPVQAQRWLAASCHGAEELA 238
Cdd:PRK08999 162 QLRAPQLPPAAYRALARAALGLCRRaGAQLLLNGDPELAEDLGADGVHLTSAQLAAL-AARPLPAGRWVAASCHDAEELA 240

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 504410385 239 LAAALEVDFVTLSPVQSTATHPGAPTLGWQRAADLLSGFDRPVFLLGGLQVGDMGRARQIGAQGIAAIRAFW 310
Cdd:PRK08999 241 RAQRLGVDFAVLSPVQPTASHPGAAPLGWEGFAALIAGVPLPVYALGGLGPGDLEEAREHGAQGIAGIRGLW 312

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: 177.26 E-value: 5.16e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   4 IHVAAAVIRGpESSVLIAKRPLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQVLLD 83
Cdd:cd03425    1 IEVVAAIIVD-DGRVLIAQRPEGKHLAGLWEFPGGKVEPGETPEQALVRELREELGIEVEVGEPLGTVEHDYPDFHVRLH 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 504410385  84 VWEVLAFAGEPHGAEGQPLAWVAPEELVDYSFPAANRPIVTA 125
Cdd:cd03425   80 VYLCTLWSGEPQLLEHQELRWVTPEELDDLDWLPADIPIVEA 121

8-oxo-dGTP diphosphatase MutT;

Pssm-ID: 182721 [Multi-domain] Cd Length: 129 Bit Score: 151.68 E-value: 6.89e-46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   1 MKRIHVAAAVIRGPESSVLIAKRPLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQV 80
Cdd:PRK10776   1 MKKLQIAVGIIRNPNNEIFITRRAADAHMAGKWEFPGGKIEAGETPEQALIRELQEEVGITVQHATLFEKLEYEFPDRHI 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 504410385  81 LLDVWEVLAFAGEPHGAEGQPLAWVAPEELVDYSFPAANRPIV 123
Cdd:PRK10776  81 TLWFWLVESWEGEPWGKEGQPGRWVSQVALNADEFPPANEPII 123

Thiamine monophosphate synthase [Coenzyme transport and metabolism]; Thiamine monophosphate synthase is part of the Pathway/BioSystem: Thiamine biosynthesis

Pssm-ID: 440121 [Multi-domain] Cd Length: 206 Bit Score: 135.31 E-value: 1.38e-38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385 127 RLPQHYLITPDGLAMPRLLEGIARALDGGIRLIQLRAPSLPPADYRALAERVMALCAGR-AQLMLKGPLEWVEDFPGAGW 205
Cdd:COG0352    2 TLPRLYLITDPDLCGRDLLEVLEAALAGGVDLVQLREKDLDERELLALARALRALCRAYgVPLIINDRVDLALALGADGV 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385 206 HLTAEQLRRAGSGRPVQAQRWLAASCHGAEELALAAALEVDFVTLSPVQSTATHPGA-PTLGWQRAADLLSGFDRPVFLL 284
Cdd:COG0352   82 HLGQEDLPVAEARALLGPDLIIGVSCHSLEEALRAEEAGADYVGFGPVFPTPTKPGApPPLGLEGLAWWAELVEIPVVAI 161

                        170       180
                 ....*....|....*....|....*.
gi 504410385 285 GGLQVGDMGRARQIGAQGIAAIRAFW 310
Cdd:COG0352  162 GGITPENAAEVLAAGADGVAVISAIW 187

Thiamine monophosphate synthase; Thiamine monophosphate synthase (TMP) (EC:2.5.1.3) catalyzes the substitution of the pyrophosphate of 2-methyl-4-amino-5- hydroxymethylpyrimidine pyrophosphate by 4-methyl-5- (beta-hydroxyethyl)thiazole phosphate to yield thiamine phosphate. This Pfam family also includes the regulatory protein TENI, a protein from Bacillus subtilis that regulates the production of several extracellular enzymes by reducing alkaline protease production. While TenI shows high sequence similarity with thiamin phosphate synthase, the purified protein has no thiamin phosphate synthase activity. Instead, it is a thiazole tautomerase.

Pssm-ID: 426849 [Multi-domain] Cd Length: 180 Bit Score: 126.51 E-value: 1.83e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  132 YLITPDGLAMPRLLEGIARALDGGIRLIQLRAPSLPPADYRALAERVMALCAGR-AQLMLKGPLEWVEDFPGAGWHLTAE 210
Cdd:pfam02581   2 YLVTDPGLDGEDLLEVVEEALKGGVTIVQLREKELDDREFLELAKELRALCRKYgVPLIINDRVDLALAVGADGVHLGQD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  211 QLRRAGSGRPVQAQRWLAASCHGAEELALAAALEVDFVTLSPVQSTATHPGAPTLGWQRAADLLSGFDRPVFLLGGLQVG 290
Cdd:pfam02581  82 DLPVAEARELLGPDLIIGVSTHTLEEALEAEALGADYIGFGPIFPTPTKPDAPPLGLEGLKAIAEAVEIPVVAIGGITPE 161

                         170
                  ....*....|....*....
gi 504410385  291 DMGRARQIGAQGIAAIRAF 309
Cdd:pfam02581 162 NVPEVIEAGADGVAVVSAI 180

NUDIX domain;

Pssm-ID: 464330 [Multi-domain] Cd Length: 114 Bit Score: 113.95 E-value: 1.64e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385    7 AAAVIRGPESSVLIAKRPLDKHQGGLWEFPGGKVEDGESVESALARelQEELGIEVTQAQPlIQVRHDYPDKQVLLDVWE 86
Cdd:pfam14815   1 AVLVIRNGDGRVLLRKRPEKGLLGGLWEFPGGKVEPGETLEEALAR--LEELGIEVEVLEP-GTVKHVFTHFRLTLHVYL 77

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 504410385   87 VLAFAGEPhgAEGQPLAWVAPEELVDYSFPAANRPIVTA 125
Cdd:pfam14815  78 VREVEGEE--EPQQELRWVTPEELDKYALPAAVRKILEA 114

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

Pssm-ID: 182536 [Multi-domain] Cd Length: 135 Bit Score: 114.45 E-value: 1.86e-31

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   1 MKRIHVAAAVIRgPESSVLIAKRPLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQV 80
Cdd:PRK10546   1 MKMIDVVAAIIE-RDGKILLAQRPAHSDQAGLWEFAGGKVEPGESQPQALIRELREELGIEATVGEYVASHQREVSGRRI 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 504410385  81 LLDVWEVLAFAGEPHGAEGQPLAWVAPEELVDYSFPAANRPIVTA 125
Cdd:PRK10546  80 HLHAWHVPDFHGELQAHEHQALVWCTPEEALRYPLAPADIPLLEA 124

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 103.13 E-value: 2.89e-27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   1 MKRI--HVAAAVIRGPESSVLIAKRPlDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDK 78
Cdd:COG1051    1 MTKVpkVAVDAVIFRKDGRVLLVRRA-DEPGKGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHPDRGH 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 504410385  79 QVLLdVWEVLAFAGEPH-GAEGQPLAWVAPEELVDYSFPAANRPIV 123
Cdd:COG1051   80 VVSV-AFLAEVLSGEPRaDDEIDEARWFPLDELPELAFTPADHEIL 124

Thiamine monophosphate synthase (TMP synthase)/TenI. TMP synthase catalyzes an important step in the thiamine biosynthesis pathway, the substitution of the pyrophosphate of 2-methyl-4-amino-5- hydroxymethylpyrimidine pyrophosphate by 4-methyl-5- (beta-hydroxyethyl) thiazole phosphate to yield thiamine phosphate. TenI is a enzymatically inactive regulatory protein involved in the regulation of several extracellular enzymes. This superfamily also contains other enzymatically inactive proteins with unknown functions.

Pssm-ID: 238317 [Multi-domain] Cd Length: 196 Bit Score: 97.97 E-value: 1.55e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385 132 YLITPDGLAMPRLLEGIARALDGGIRLIQLRAPSLPPADYRALAERVMALCA---------GRAQLMLKGPLEWV----E 198
Cdd:cd00564    2 YLITDRRLDGEDLLEVVEAALKGGVTLVQLREKDLSARELLELARALRELCRkygvpliinDRVDLALAVGADGVhlgqD 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385 199 DFPgagwhltAEQLRRAgsgrpVQAQRWLAASCHGAEELALAAALEVDFVTLSPVQSTATHPGA-PTLGWQRAADLLSGF 277
Cdd:cd00564   82 DLP-------VAEARAL-----LGPDLIIGVSTHSLEEALRAEELGADYVGFGPVFPTPTKPGAgPPLGLELLREIAELV 149

                        170       180       190
                 ....*....|....*....|....*....|...
gi 504410385 278 DRPVFLLGGLQVGDMGRARQIGAQGIAAIRAFW 310
Cdd:cd00564  150 EIPVVAIGGITPENAAEVLAAGADGVAVISAIT 182

mutator mutT protein; All proteins in this family for which functions are known are involved in repairing oxidative damage to dGTP (they are 8-oxo-dGTPases). This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). Lowering the threshold picks up members of MutT superfamily well. [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 200031 [Multi-domain] Cd Length: 128 Bit Score: 94.56 E-value: 5.19e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385    1 MKRIHVAAAVIRGPESSVLIAKRPLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQV 80
Cdd:TIGR00586   1 KKLQQIAVGIIRNENGEIIITRRADGHMFAKLLEFPGGKEEGGETPEQAVVRELEEEIGIPQHFSEFEKLEYEFYPRHIT 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 504410385   81 LLdVWEVLAFAGEPHGAEGQP-LAWVAPEELVDYSFPAANRPIVTAARL 128
Cdd:TIGR00586  81 LW-FWLLERWEGGPPGKEGQPeEWWVLVGLLADDFFPAANPVIIKLLRL 128

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: 88.55 E-value: 1.70e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   2 KRIHVAAAVIRGPESSVLIAKRPLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRH-DYPDKQV 80
Cdd:COG0494   11 HYRPAVVVVLLDDDGRVLLVRRYRYGVGPGLWEFPGGKIEPGESPEEAALRELREETGLTAEDLELLGELPSpGYTDEKV 90

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 504410385  81 ---LLDVWEVLAFAGEPHGAEGQPLAWVAPEELVDYSFPAANRPIVTAARLPQ 130
Cdd:COG0494   91 hvfLARGLGPGEEVGLDDEDEFIEVRWVPLDEALALVTAGEIAKTLAALARLL 143

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 78.68 E-value: 5.03e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385    6 VAAAVIRGPESSVLIAKRPlDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQVLLD-V 84
Cdd:pfam00293   5 AVGVVLLNEKGRVLLVRRS-KKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRFPDeH 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 504410385   85 WEVLAFAGEPHG-------AEGQPLAWVAPEELVDYSFPAANRPIV 123
Cdd:pfam00293  84 EILYVFLAEVEGelepdpdGEVEEVRWVPLEELLLLKLAPGDRKLL 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: 76.67 E-value: 1.30e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   5 HVAAAVIRGPESSVLIAKRPlDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPD--KQVLL 82
Cdd:cd02883    1 VAVGAVVFDDEGRVLLVRRS-DGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDegRHVVV 79

                         90       100
                 ....*....|....*....|....*.
gi 504410385  83 DVWEVLAFAGEPH---GAEGQPLAWV 105
Cdd:cd02883   80 LVFLARVVGGEPPpldDEEISEVRWV 105

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: 72.66 E-value: 5.24e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   9 AVIRGpESSVLIAKRPLDKhqGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPL--IQVRHDyPDKQVLLdvwe 86
Cdd:cd04699    7 GVIFD-NGRVLLLRRSRAG--AGEWELPGGRLEPGESPEEALKREVKEETGLDVSVGELLdtWTFELD-PDKGVFI---- 78

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 504410385  87 vLAFAGEPhgAEGQPL--------AWVAPEELVDYSFP 116
Cdd:cd04699   79 -VTYLCRL--VGGEVTlsdeheeyEWVTPEELAELELP 113

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: 68.69 E-value: 2.16e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   6 VAAAVIRGPEssVLIAKR--PLDKhqgGLWEFPGGKVEDGESVESALARELQEELGIEVTqAQPLIQVRhDYPDKQVLLD 83
Cdd:cd04673    4 VGAVVFRDGR--VLLVRRgnPPDA---GLWSFPGGKVELGETLEDAALRELREETGLEAE-VVGLLTVV-DVIERDEAGR 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 504410385  84 V---WEVLAFAGEPHGAEGQP------LAWVAPEELVDYSFPAANRPIVTAA 126
Cdd:cd04673   77 VrfhYVILDFLAEWVSGEPVAgddaldARWFSLEELDGLPLTPGTRDVLERA 128

Adenine-specific DNA glycosylase, acts on AG and A-oxoG pairs [Replication, recombination and repair];

Pssm-ID: 440807 [Multi-domain] Cd Length: 350 Bit Score: 71.71 E-value: 3.90e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   2 KRIHVAAAVIRgPESSVLIAKRPLDKHQGGLWEFPGGKVEDGESVEsALARELQEELGIEVTQAQPLIQVRHDYPDKQVL 81
Cdd:COG1194  228 PERYGAALVIR-DDGRVLLEKRPPKGLWGGLWEFPEFEWEEAEDPE-ALERWLREELGLEVEWLEPLGTVRHVFTHFRLH 305

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 504410385  82 LDVWevLAFAGEPHGAEGQPLAWVAPEELVDYSFPAANRPIVTAAR 127
Cdd:COG1194  306 LTVY--LARVPAGPPAEPDGGRWVPLEELAALPLPAPMRKLLKALL 349

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: 66.79 E-value: 9.33e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   6 VAAAVIRGPESSVLIAKrpldKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVT--QAQPLIQVR---HDYPDKQV 80
Cdd:cd04690    2 VKAAVIIIKDGRLLLVR----KRGTDAFYLPGGKREPGETPLQALVRELKEELGLDLDpdSLRFLGTFEapaANEPGTTV 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 504410385  81 LLDVWEVlAFAGEPH-GAEGQPLAWVAPEELVDYSFPAANRPIV 123
Cdd:cd04690   78 RMTCFTA-DYDGEPQpAAEIEELRWLDPADPDDDRLAPLLREIV 120

MutT homolog-1 (MTH1); MutT homolog-1 (MTH1; EC 3.6.1.- ), also called nucleoside diphosphate-linked moiety X)) motif 1 (Nudt1), is a member of the NUDIX hydrolase superfamily. MTH1, the mammalian counterpart of MutT, hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-ATP, to monophosphates, thereby preventing the incorporation of such oxygen radicals during replication. This is an important step in the repair mechanism in genomic and mitochondrial DNA. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity, and contain the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. MTH1 is predominantly localized in the cytoplasm and mitochondria. Structurally, this enzyme adopts a similar fold to MutT despite low sequence similarity outside the conserved NUDIX motif. The most distinctive structural difference between MutT and MTH1 is the presence of a beta-hairpin, which is absent in MutT. This results in a much deeper and narrower substrate binding pocket. Mechanistically, MTH1 contains dual specificity for nucleotides that contain 2-OH-adenine bases and those that contain 8-oxo-guanine bases.

Pssm-ID: 467533 [Multi-domain] Cd Length: 136 Bit Score: 64.47 E-value: 8.75e-13

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 504410385  31 GLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQVLLD--VWEVLAFAGEP 94
Cdd:cd03427   27 GKWNGFGGKVEPGETIEEAAVRELEEEAGLTATELEKVGRLKFEFPDDPEAMDvhVFRADSWTGEP 92

thiamine phosphate synthase;

Pssm-ID: 234590 [Multi-domain] Cd Length: 212 Bit Score: 65.97 E-value: 9.50e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385 132 YLITPDGLAMPR-LLEGIARALDGGIRLIQLRAPSLPPADYRALAERVMALCAG---------RAQLMLKGPLEWV---- 197
Cdd:PRK00043  10 YLITDSRDDSGRdLLEVVEAALEGGVTLVQLREKGLDTRERLELARALKELCRRygvplivndRVDLALAVGADGVhlgq 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385 198 EDFPgagwhltAEQLRRAgsgrpVQAQRWLAASCHGAEELALAAALEVDFVTLSPVQSTATHPGAPtlgwqrAADLLSGF 277
Cdd:PRK00043  90 DDLP-------VADARAL-----LGPDAIIGLSTHTLEEAAAALAAGADYVGVGPIFPTPTKKDAK------APQGLEGL 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 504410385 278 --------DRPVFLLGGLqvgDMGRARQI---GAQGIAAIRA 308
Cdd:PRK00043 152 reiraavgDIPIVAIGGI---TPENAPEVleaGADGVAVVSA 190

thiamine-phosphate diphosphorylase; This model represents the thiamine-phosphate pyrophosphorylase, ThiE, of a number of bacteria, and N-terminal domains of bifunctional thiamine proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe, in which the C-terminal domain corresponds to the bacterial hydroxyethylthiazole kinase (EC 2.7.1.50), ThiM. This model includes ThiE from Bacillus subtilis but excludes its paralog, the regulatory protein TenI (SP:P25053), and neighbors of TenI. [Biosynthesis of cofactors, prosthetic groups, and carriers, Thiamine]

Pssm-ID: 273222 [Multi-domain] Cd Length: 196 Bit Score: 65.35 E-value: 1.58e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  132 YLITPDGLAMPRLLEGIARALDGGIRLIQLRAPSLPPADYRALAERVMALCAGR-AQLMLKGPLEWVEDFPGAGWHLTAE 210
Cdd:TIGR00693   3 YLITDPQDGPADLLNRVEAALKGGVTLVQLRDKGSNTRERLALAEKLQELCRRYgVPFIVNDRVDLALALGADGVHLGQD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  211 QLRRAGSGRPVQAQRWLAASCHGAEELALAAALEVDFVTLSPVQSTATHPGAPTL----GWQRAADLLsgFDRPVFLLGG 286
Cdd:TIGR00693  83 DLPASEARALLGPDKIIGVSTHNLEELAEAEAEGADYIGFGPIFPTPTKKDPAPPagveLLREIAATL--IDIPIVAIGG 160

                         170       180
                  ....*....|....*....|....
gi 504410385  287 LQVGDMGRARQIGAQGIAAIRAFW 310
Cdd:TIGR00693 161 ITLENAAEVLAAGADGVAVVSAIM 184

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: 61.50 E-value: 9.27e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   4 IHVAAAVIRGPESSVLIAKRplDKHQG----GLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPliQVRHDYPDKQ 79
Cdd:cd18882    1 HEVAIAILYDDRGKVLLQLR--DDKPGipypGYWGLFGGHLEPGETPEEAIRRELEEEIGYEPGEFRF--FLLYTEDDGE 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 504410385  80 vllDVWEVLAFAgePHGA--------EGQPLAWVAPEELVDYSFPAANRPIV 123
Cdd:cd18882   77 ---DRIRHVFHA--PLDVdlsdlvlnEGQALRLFSPEEILQGPLYSNLAGIL 123

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: 61.04 E-value: 1.05e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   8 AAVIRGPESSVLIAKRpLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQpLIQVRHDY--PDKQVLLDVW 85
Cdd:cd04678    6 GVIVLNDDGKVLLGRR-KGSHGAGTWALPGGHLEFGESFEECAAREVLEETGLEIRNVR-FLTVTNDVfeEEGKHYVTIF 83

                         90       100       110
                 ....*....|....*....|....*....|..
gi 504410385  86 -------EVLAFAGEPHGAEGqpLAWVAPEEL 110
Cdd:cd04678   84 vlaevddGEPEENMEPDKCEG--WEWFSWDEL 113

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

Pssm-ID: 467586 [Multi-domain] Cd Length: 125 Bit Score: 60.38 E-value: 1.85e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   8 AAVIRGPESSVLIAKRPldkHQGGLWEFPGGKVEDGESVESALARELQEELGIEVT-----QAQPLIQVRHDYPDKQ-VL 81
Cdd:cd18874    6 GALIFNPDGKVLLVRSH---KWNDLYGIPGGKVEWGETLEEALKREVKEETGLDITdirfiLVQESINSEEFHKPAHfVF 82

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 504410385  82 LDVwevlaFAGEPHGA-----EGQPLAWVAPEELVDYS 114
Cdd:cd18874   83 VDY-----LARTDSSEvvlneEAVEYLWVEPEEALKYP 115

thiamine phosphate synthase;

Pssm-ID: 235054 [Multi-domain] Cd Length: 347 Bit Score: 63.36 E-value: 2.68e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385 109 ELVDYSFPAANRPIVTAARLpqhYLITPDGlamPRLLEGIARALDGGIRLIQLRAPSLPPADYRALAERVMALCAGRAQL 188
Cdd:PRK02615 130 ELLNASLGKKRRQRLKDARL---YLITSPS---ENLLEVVEAALKGGVTLVQYRDKTADDRQRLEEAKKLKELCHRYGAL 203

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385 189 MLkgplewVEDFP------GA-GWHLTAEQLRRAGSGRPVQAQRWLAASCHGAEELALAAALEVDFVTLSPVQSTATHPG 261
Cdd:PRK02615 204 FI------VNDRVdialavDAdGVHLGQEDLPLAVARQLLGPEKIIGRSTTNPEEMAKAIAEGADYIGVGPVFPTPTKPG 277

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 504410385 262 APTLGWQRAADLLSGFDRPVFLLGGLQVGDMGRARQIGAQGIAAIRA 308
Cdd:PRK02615 278 KAPAGLEYLKYAAKEAPIPWFAIGGIDKSNIPEVLQAGAKRVAVVRA 324

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: 60.23 E-value: 4.53e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   6 VAAAVIRGPESSVLIAKR-PLDKHQGGLWEF-PGGKVEDGESVESALARELQEELGIEVT--QAQPLIQVRHDypdkQVL 81
Cdd:cd04693   31 VVHVWIFNSDGEILIQQRsPDKKGFPGMWEAsTGGSVLAGETSLEAAIRELKEELGIDLDadELRPILTIRFD----NGF 106


                 ....*.
gi 504410385  82 LDVWEV 87
Cdd:cd04693  107 DDIYLF 112

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: 59.62 E-value: 5.21e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   4 IHVAAAVIrgPESS---VLIAKRPLD-KHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQaqpliqvrhdyPDKQ 79
Cdd:cd04694    1 VDVGVVVL--IEDSddrVLLTRRAKHmRTFPGVWVPPGGHVELGESLLEAGLRELQEETGLEVSD-----------IQSL 67


                 ....*..
gi 504410385  80 VLLDVWE 86
Cdd:cd04694   68 SLLGLWE 74

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: 58.72 E-value: 9.88e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  18 VLIAKRPldkhQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQVLldVW-EVLAFAGEPHG 96
Cdd:cd03673   18 VLLIHRP----RYDDWSLPKGKLEPGETPEEAAVREVEEETGLRVRLGRPLGTTRYTYTRKGKG--ILkKVHYWLMRALG 91

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 504410385  97 AEGQP--------LAWVAPEELVDYSFPAANRPIVTAAR 127
Cdd:cd03673   92 GEFLPqpeeeideVRWLPPDEARRLLTYPSDREVLDAAL 130

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

Pssm-ID: 467596 [Multi-domain] Cd Length: 147 Bit Score: 58.78 E-value: 1.16e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  31 GLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQV--LLDVWEVLAFAGEPH--GAEGqPLAWVA 106
Cdd:cd18886   25 GKWNGVGGKLEPGESPEECAIREVFEETGLELEDLQLRGIVTFPSFDGGEdwLMYVFLAEAFSGELVesDREG-ILAWVP 103


                 ....*..
gi 504410385 107 PEELVDY 113
Cdd:cd18886  104 IDWLLNL 110

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: 57.92 E-value: 1.42e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   3 RIHVAAAVIRgpESSVLIAKrpLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTqAQPLIQVRhDY--PDKQV 80
Cdd:cd18880    1 RIRAKAIIIE--DGKLLLVK--HRDEGGIFYILPGGGQEHGETLPEALKRECLEETGLDVE-VGDLLFVR-EYigPNKPV 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 504410385  81 L-LDVW-EVLAFAGEPH-GAEGQP----LAWVAPEELVDY-SFPAANRPIV 123
Cdd:cd18880   75 HqVELFfLCTLEGGELTlGSDPDLnqvgVEWIPLEELDSIrLYPAILRELI 125

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

Pssm-ID: 467564 [Multi-domain] Cd Length: 135 Bit Score: 57.58 E-value: 2.08e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   6 VAAAV---IRGPESsVLIAKRPLD--KhqgGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQV 80
Cdd:cd04681    5 VAAAVgviIRNEGE-ILFVRRAKEpgK---GKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYLCSLPNTYLYKGI 80


                 .
gi 504410385  81 L 81
Cdd:cd04681   81 T 81

C-terminal domain of DNA glycosylase; DNA glycosylase (MutY in bacteria and hMYH in humans) is responsible for repairing misread A*oxoG residues to C*G by removing the inappropriately paired adenine base from the DNA backbone. It belongs to the NUDIX hydrolase superfamily and is important for the repair of various genotoxic lesions. Enzymes belonging to this superfamily requires a divalent cation, such as Mg2+ or Mn2+ for their activity. They are also recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V). However, DNA glycosylase does not seem to contain this signature motif. DNA glycosylase consists of 2 domains: the N-terminal domain contains the catalytic properties of the enzyme and the C-terminal domain affects substrate (oxoG) binding and enzymatic turnover. The C-terminal domain is highly similar to MutT, based on secondary structure and topology, despite low sequence identity. MutT sanitizes the nucleotide precursor pool by hydrolyzing oxo-dGTP to oxo-dGMO and inorganic pyrophosphate. The similarity strongly suggests that the two proteins share a common evolutionary origin.

Pssm-ID: 467537 [Multi-domain] Cd Length: 118 Bit Score: 56.16 E-value: 5.29e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   2 KRIHVAAAVIRGPESsVLIAKRP----LdkhqGGLWEFPGGKVEDGESVESALARELQEELGIEVtqaQPLIQVRHdypd 77
Cdd:cd03431    2 PERYFTVLVLRDGGR-VLLEKRPekglL----AGLWEFPLVETEEEEEEAEALLGLLAEELLLIL---EPLGEVKH---- 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 504410385  78 kqVL------LDVWEVlaFAGEPHGAEGQPLAWVAPEELVDYSFPAANR 120
Cdd:cd03431   70 --VFshfrlhITVYLV--ELPEAPPAAPDEGRWVDLEELDEYALPAPMR 114

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

Pssm-ID: 467588 [Multi-domain] Cd Length: 121 Bit Score: 56.06 E-value: 5.39e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   7 AAAVIRGPESSVLIAKRPLDKHqgglWEFPGGKVEDGESVESALARELQEELGIEVTQAQPL----IQVRHDYPDKQVLL 82
Cdd:cd18876    3 AGALFTDAAGRVLLVKPTYKDG----WELPGGVVEAGESPLQAARREVREELGLDVPVGRLLavdwVPPAGGGDDAVLFV 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 504410385  83 dvwevlaFAGEPHGAEGQPLAWVAPEELVDYSFpaanrpiVTAARLPQH 131
Cdd:cd18876   79 -------FDGGVLTPEQAAAIRLQDEELSAYRF-------VTPEEAAEL 113

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

Pssm-ID: 467573 [Multi-domain] Cd Length: 122 Bit Score: 55.77 E-value: 8.94e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   6 VAAAVIRgpESSVLIAKRpldKHQG--GLWEFPGGKVEDGESVESALARELQEELGIEvTQAQPLIQVRhDYPDKQVLLD 83
Cdd:cd04691    4 VGGVVVK--EGKVLLVKR---AYGPgkGRWTLPGGFVEEGETLDEAIVREVLEETGID-AKPVGIIGVR-SGVIRDGKSD 76

                         90       100       110
                 ....*....|....*....|....*....|...
gi 504410385  84 ---VWEVLAFAGEP--HGAEGQPLAWVAPEELV 111
Cdd:cd04691   77 nyvVFLLEYVGGEPkpDERENSEAGFLTLEEAL 109

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: 54.48 E-value: 2.46e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   7 AAAVIRgPESSVLIAKrpldKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPL--IQVRHDYPDKQV--LL 82
Cdd:cd04688    5 VAAIII-RDGKVLLAR----GEDDDYYRLPGGRVEFGETSEDALVREFKEELGVEVEVVRLLfvVENFFTYDGKPFheIG 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 504410385  83 DVWEV-------LAFAGEPHGAEGQPL--AWVAPEELVDY 113
Cdd:cd04688   80 FYYLVelsdealYEQDIFFLEEDGEKLefRWIPLEELDEI 119

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

Pssm-ID: 467566 [Multi-domain] Cd Length: 137 Bit Score: 54.53 E-value: 3.07e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  15 ESSVLIAKRPLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQA--QPLIQVRHDYPDKQVLLDV-WEVLAFA 91
Cdd:cd04683   10 GDEVLLLRRANTGYDDGWWHLPAGHVEAGETVRAAAVREAKEELGVEIDPEdlRLVHTMHRRSDGGRERIDFfFRATRWS 89

                         90       100
                 ....*....|....*....|....*....
gi 504410385  92 GEPHGAEGQP---LAWVA----PEELVDY 113
Cdd:cd04683   90 GEPRNREPDKcaeLRWFPldalPENTVPY 118

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: 54.55 E-value: 4.04e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   4 IHVAAAV-IRGPESSVLIAKRPLDKH-QGGLWE-FPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQV 80
Cdd:cd04697   25 IHRATYIvVRNAAGRLLVQKRTMDKDyCPGYLDpATGGVVGAGESYEENARRELEEELGIDGVPLRPLFTFYYEDDRSRV 104

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 504410385  81 LLDVWEVLafagepHGAEGQPlawvAPEELVDYSFpaanRPIVTAARLPQHYLITPDGL-AMPRLLE 146
Cdd:cd04697  105 WGALFECV------YDGPLKL----QPEEVAEVDW----MSEDEILQAARGEEFTPDGRvALERYLA 157

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: 53.67 E-value: 5.55e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   7 AAAVIRGPESSVLIAKRPldkhQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQpLIQV------RHDYP--DK 78
Cdd:cd04677   15 AAVIILNEQGRILLQKRT----DTGDWGLPGGAMELGESLEETARREVFEETGLTVEELE-LLGVysgkdlYYTYPngDE 89

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 504410385  79 -QVLLDVWEVLAFAGEPH--GAEGQPLAWVAPEEL 110
Cdd:cd04677   90 vYNVTAVYLVRDVSGELKvdDEESLELRFFSLDEL 124

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: 54.05 E-value: 6.09e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   4 IHVaaaVIRGPESSVLIAKRPLDK-HQGGLWEFP-GGKVEDGESVESALARELQEELGIEVTQA-QPLIQVRHDYPDKQV 80
Cdd:COG1443   32 FSV---FVFNSDGRLLLQRRALTKdHWPGLWDNTvCGHPRAGETYEEAAVRELEEELGITVDDDlRPLGTFRYRAVDANG 108

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 504410385  81 LLDvWEVLA-FAGEPHGA-EGQP-----LAWVAPEELVD 112
Cdd:COG1443  109 LVE-NEFCHvFVARLDGPlTPQPeevaeVRWVTLEELLA 146

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

Pssm-ID: 467587 [Multi-domain] Cd Length: 144 Bit Score: 53.34 E-value: 8.60e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 504410385   4 IHVAAAVIRGPESSVLIAKRPLDKHQGglWEFPGGKVEDGESVESALARELQEELGIEVTQ 64
Cdd:cd18875    2 ELTNMCMIYDGEDRVLVLDRVKKDWGG--YTFPGGHVEPGESFVDSVIREVKEETGLTIKN 60

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: 51.80 E-value: 2.90e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   7 AAAVIRGPESSVLIAKRpldKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRH----DYPDKQVLL 82
Cdd:cd03671    6 VGIVLFNRDGQVLVGRR---IDVPGAWQFPQGGIDEGEDPEEAALRELYEETGLSPEDVEIIAETPDwltyDLPEDLIRK 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 504410385  83 D----------VWEVLAFAGE--------PHGAEGQPLAWVAPEELVDYSFP 116
Cdd:cd03671   83 GwggkyrgqkqKWFLFRFTGDdseinldtHEHPEFDAWRWVDLEELPDLVVP 134

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: 51.74 E-value: 2.94e-08

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 504410385  32 LWEFPGGKVEDGESVESALARELQEELGIEVTQAQPL 68
Cdd:cd03424   30 LLELPAGKIDPGEDPEEAARRELEEETGYTAGDLELL 66

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: 51.15 E-value: 3.80e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   3 RIHVAAAVIRgpESSVLIAKRPLDKHQGGlWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQV-- 80
Cdd:cd04679    2 RVGCGAAILD--DGRLLLVLRLRAPEAGH-WGLPGGKVDWLETVEDAVRREILEELGLEIELTRLLCVVDQIDAADGEhw 78

                         90
                 ....*....|....
gi 504410385  81 LLDVWEVLAFAGEP 94
Cdd:cd04679   79 VAPVYLAEIFSGEP 92

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: 50.37 E-value: 5.66e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  31 GLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQ---VRHDYPDKQVLLDV--WEVLAFAGEPHGAEGQPLAWV 105
Cdd:cd04682   28 NLWDLPGGGREGDETPFACVLRELREELGLALPEDRLVWErvyPSNHNPGRQSWFFVarLPADEVDAIRFGDEGQEWALM 107


                 ....*..
gi 504410385 106 APEELVD 112
Cdd:cd04682  108 PVDDFLA 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: 467594 Cd Length: 136 Bit Score: 50.93 E-value: 6.12e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 504410385   5 HVAAAVIRGPESsVLIAKRPLDKHqgglWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQVL 81
Cdd:cd18883    1 YTARGVIISDEH-LLLARVKGDDK----TFLPGGHIEIGESAEIALVRELREELGLSCKVGRYLGAVENQWQDKEVI 72

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: 50.33 E-value: 6.72e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  33 WEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQV---RHDYPDKQVLLDVweVLAFAGEP---HGAEGQPLAWVA 106
Cdd:cd04680   25 WYLPGGGVDKGETAEEAARRELREEAGVVLTGPPRLFGVyfnRRVSPRDHVALYR--VREFEQTEppePNGEIAEAGFFA 102

                         90
                 ....*....|....*.
gi 504410385 107 PEELVDYSFPAANRPI 122
Cdd:cd04680  103 LDALPEDTTPATRRRL 118

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

Pssm-ID: 467554 [Multi-domain] Cd Length: 131 Bit Score: 50.23 E-value: 7.76e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 504410385   6 VAAAVIRgPESSVLIAKrplDKHQG-GLWEFPGGKVEDGESVESALARELQEELGIEvTQAQPLIQVRH 73
Cdd:cd04670    5 VGGLVIN-ENNEVLVVQ---EKYGGpGGWKLPGGLVDPGEDIGEAAVREVFEETGID-TEFVSILGFRH 68

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

Pssm-ID: 467569 [Multi-domain] Cd Length: 130 Bit Score: 50.37 E-value: 7.92e-08

                         10        20        30
                 ....*....|....*....|....*....|...
gi 504410385  31 GLWEFPGGKVEDGESVESALARELQEELGIEVT 63
Cdd:cd04686   26 GRYDLPGGSQEFGESLEDALKREFAEETGMTVT 58

nucleoside triphosphatase NudI; Provisional

Pssm-ID: 185369 [Multi-domain] Cd Length: 141 Bit Score: 50.13 E-value: 1.08e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  31 GLWEFPGGKVEDGESVESALARELQEELG--IEVTQAQPL-----IQVRhDYPDKQ-----VLLDVWEVLAFAGEPH-GA 97
Cdd:PRK15472  31 GQWALSGGGVEPGERIEEALRREIREELGeqLLLTEITPWtfrddIRTK-TYADGRkeeiyMIYLIFDCVSANRDVKiNE 109

                         90       100
                 ....*....|....*....|...
gi 504410385  98 EGQPLAWVAPEELVDYSFPAANR 120
Cdd:PRK15472 110 EFQDYAWVKPEDLVHYDLNVATR 132

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: 49.56 E-value: 1.30e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   6 VAAAVIRGPESS-VLIAKRPLDkhqGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQpLIQVRHD 74
Cdd:cd04664    3 VLVVIYRKDEEGeVLLLKRTDD---GGFWQSVTGGIEDGETPWQAALRELKEETGLDPLELQ-LIDLNVS 68

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: 49.93 E-value: 1.35e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  15 ESSVLIAKRPLDKHQ-GGLWEFPGGKVEDGESVESALARELQEELGIE--VTQAQPLIqVRHD-----YPD--KQVLLDV 84
Cdd:cd04696   12 EGCYLLCKMADDRGVfPGQWALSGGGVEPGERIEEALRREIREELGEQliLSDITPWT-FRDDiriktYPDgrQEEIYMI 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 504410385  85 WEVLAFAGEPHGA----EGQPLAWVAPEELVDYSFPAANR 120
Cdd:cd04696   91 YLIFDCVSANRDVcindEFQDYAWVKPADLANYDLNVATR 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: 467589 [Multi-domain] Cd Length: 141 Bit Score: 49.28 E-value: 2.05e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   6 VAAAVIRGPEssVLIAKRPLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIevtqaqPLIQVRHDyPDKQVLLDVW 85
Cdd:cd18877   24 FAPAEDGGPH--VLLQHRAWWTHQGGTWALPGGARDSGETPEAAALRETEEETGL------DADTLRVV-GTHVDDHGGW 94

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 504410385  86 E---VLAFAGEP-----HGAEGQPLAWVAPEELVDY 113
Cdd:cd18877   95 SyttVLASAPEPlpvrpANEESVELRWVPLDEVESL 130

RNA pyrophosphohydrolase; Reviewed

Pssm-ID: 234820 [Multi-domain] Cd Length: 156 Bit Score: 49.00 E-value: 3.65e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 504410385   8 AAVIRGPESSVLIAKRPLDKHqggLWEFPGGKVEDGESVESALARELQEELGI 60
Cdd:PRK00714  12 GIILLNRQGQVFWGRRIGQGH---SWQFPQGGIDPGETPEQAMYRELYEEVGL 61

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: 47.54 E-value: 8.33e-07

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 504410385  18 VLIAKRPLDKHQGGlWEFPGGKVEDGESVESALARELQEELGIEV 62
Cdd:cd18873   19 VLLIKRKNEPFKGG-WALPGGFVREDETLEDAARRELREETGLKD 62

RNA pyrophosphohydrolase; The initiation of mRNA degradation often requires deprotection of its 5' end. In eukaryotes, the 5'-methylguanosine (cap) structure is principally removed by the NUDIX family decapping enzyme Dcp2, yielding a 5'-monophosphorylated RNA that is a substrate for 5' exoribonucleases. In bacteria, the 5'-triphosphate group of primary transcripts is also converted to a 5' monophosphate by a NUDIX protein called RNA pyrophosphohydrolase (RppH), allowing access to both endo- and 5' exoribonucleases. 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: 467550 [Multi-domain] Cd Length: 121 Bit Score: 47.24 E-value: 8.86e-07

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 504410385  33 WEFPGGKVEDGESVESALARELQEELGIEVTQAQPL 68
Cdd:cd04665   24 WEFPGGKREPGETIEEAARRELYEETGAVIFELKPL 59

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

Pssm-ID: 467552 [Multi-domain] Cd Length: 117 Bit Score: 46.89 E-value: 9.41e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 504410385   7 AAAVIRGPESSVLIAKRpldkhqGGLWEFPGGKVEDGESVESALARELQEELGI 60
Cdd:cd04667    3 ATVICRRGDRILLVARR------GGRWLLPGGKIEPGESPLEAAIRELKEETGL 50

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

Pssm-ID: 467568 [Multi-domain] Cd Length: 138 Bit Score: 47.18 E-value: 1.09e-06

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 504410385  33 WEFPGGKVEDGESVESALARELQEELGIEVTQAQPL 68
Cdd:cd04685   30 WFTPGGGVEPGESPEQAAVRELREETGLRLEPDDLG 65

nucleoside diphosphate-linked moiety X)) motif 16; U8 SnoRNA-decapping enzyme, also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 16/Nudt16, is encoded by the human NUDT16 gene and a RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. 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: 467581 Cd Length: 175 Bit Score: 47.74 E-value: 1.19e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   3 RIHVAAAVIRGPESSVLIAKRPLdKHQ-------GGLWEFPGGKVEDGESVESALARELQEELG-----IEVTQAQPLIQ 70
Cdd:cd18869    2 YRHACHAMLYAPNPGKLFGRYPI-RATllmqmrfDGLLGFPGGFVDTGESLEEGLNRELREELGlahavFPVTEDDYRSS 80

                         90
                 ....*....|.
gi 504410385  71 VRHDYPDKQVL 81
Cdd:cd18869   81 HVREGPKRLVL 91

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

Pssm-ID: 467553 [Multi-domain] Cd Length: 120 Bit Score: 46.58 E-value: 1.27e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 504410385   7 AAAVIRGPESSVLIAK-RPLDKHqgglWEFPGGKVEDGESVESALARELQEELGIEV 62
Cdd:cd04669    3 AVLVIYDDDKLLLIRRtKPGEEY----YVFPGGGIEPGETPEEAALREAVEELGLDV 55

nucleoside triphosphatase YtkD; The functional assignment to the proteins of this family is contentious, with papers disagreeing in both interpretation and enzyme assay results. This protein belongs to the nudix family and shares some sequence identity with E. coli MutT but appears not to be functionally interchangeable with it. [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 131752 Cd Length: 156 Bit Score: 46.60 E-value: 2.31e-06

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 504410385   25 LDKHQGGLWEFPGGKVEDGESVESALARELQEELG 59
Cdd:TIGR02705  39 LTEHKRRGLEFPGGKVEPGETSKEAAIREVMEETG 73

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: 46.10 E-value: 2.68e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  31 GLWEFPGGKVEDGESVESALARELQEELGIEVT-----QAQPLIQVRHDYPDK-----QVLLDV---WEVLAFAGEPHGA 97
Cdd:cd03674   25 GRWLQPGGHVEPDEDPLEAALREAREETGLDVEllsplSPDPLDIDVHPIPANpgepaHLHLDVrylAVADGDEALRKSD 104

                         90       100
                 ....*....|....*....|.
gi 504410385  98 EGQPLAWVAPEELVDYSFPAA 118
Cdd:cd03674  105 ESSDVRWFPLDELEELSMDPN 125

coenzyme A pyrophosphatase and similar proteins; Coenzyme A pyrophosphatase (CoAse; EC 3.6.1.1), also called nucleoside diphosphate-linked moiety X)) motif 7, is a member of the NUDIX hydrolase superfamily, functions to catalyze the elimination of oxidized inactive CoA, which can inhibit CoA-utilizing enzymes. The need of CoAses mainly arises under conditions of oxidative stress. CoAse has a conserved NUDIX fold and requires a single divalent cation for catalysis. In addition to a signature NUDIX motif G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val, CoAse contains an additional motif upstream called the NuCoA motif (LLTXT(SA)X3RX3GX3FPGG) which is postulated to be involved in CoA recognition. CoA plays a central role in lipid metabolism. It is involved in the initial steps of fatty acid sythesis in the cytosol, in the oxidation of fatty acids and the citric acid cycle in the mitochondria, and in the oxidation of long-chain fatty acids in peroxisomes. CoA has the important role of activating fatty acids for further modification into key biological signalling molecules.

Pssm-ID: 467532 [Multi-domain] Cd Length: 158 Bit Score: 45.95 E-value: 3.68e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 504410385   6 VAAAVIRGP-ESSVLIAKRPLD-KHQGGLWEFPGGKVEDG-ESVESALARELQEELGIEVTQAQPL 68
Cdd:cd03426    5 VLIPLVEGDgELHVLLTKRASHlRSHPGQIAFPGGKREPGdESPVETALRETEEEIGLPPESVEVL 70

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

Pssm-ID: 467567 [Multi-domain] Cd Length: 140 Bit Score: 45.31 E-value: 4.70e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   7 AAAVIRGPESSVLIAKRPLDKHQgglweFPGGKVEDGESVESALARELQEELGIEVtQAQPLIQVRHDY---PDKQvllD 83
Cdd:cd04684   18 AYAVIFNDEGKVLLVQTPNGGYF-----LPGGGIEPGETPEEALHREVLEETGWEI-EIGEFLGNASRYfysPDYD---R 88

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 504410385  84 VWEVLA--FAGEPHGAEGQP------LAWVAPEELVD 112
Cdd:cd04684   89 YYLNIGyfYLAELVRKVSEPteedheLVWLPPEEAAD 125

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: 45.24 E-value: 5.50e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  28 HQGGLWEFPGGKVEDGES-VESALaRELQEELGIEVTQAQPLIQVRHDYP-----DKQVLLdvWevLAFAGEPH----GA 97
Cdd:cd03428   25 SYGGHWDFPKGHVEPGESeLETAL-RETKEETGLTVDDLPPGFRETLTYSfkegvEKTVVY--F--LAELTPDVevklSE 99

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 504410385  98 EGQPLAWVAPEELVDYSFPAANRPIVTAArlpQHYL 133
Cdd:cd03428  100 EHQDYKWLPYEEALQLLTYENIKELLKEA---NEYL 132

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: 43.74 E-value: 1.22e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 504410385   9 AVIRGPESSVLIAKRPLDKHQgglweFP-------GGKVEDGESVESALARELQEELGIEVTQAQ 66
Cdd:cd24154    7 AFLINSQGQLWIPRRTADKRI-----FPlaldmsvGGHVSSGETYEQAFVRELQEELNLDLDQLS 66

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: 43.63 E-value: 1.35e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   6 VAAAVIRGpESSVLIAKRPldKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQ-----AQPliqvrhdYPDKQV 80
Cdd:cd03429    4 VIVLVTNG-EDKILLARQP--RWPPGRYSLLAGFVEPGETLEEAVRREVKEEVGLRVKNvryvgSQP-------WPFPSS 73

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 504410385  81 LLdvwevLAFAGEphgAEGQPL----------AWVAPEELVDYSFPAANRPIvtAARLPQHYL 133
Cdd:cd03429   74 LM-----LGFTAE---ADSGEItvdddeledaRWFSRDELPEALFLPPPGSI--ARRLIRAWL 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: 467559 [Multi-domain] Cd Length: 144 Bit Score: 43.16 E-value: 2.91e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   8 AAVIRGPESSVLIAKrpldKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVtQAQPLIQV------RHDYPDKQ-- 79
Cdd:cd04676   21 AAVILNEDGRILLQR----KGGLGLWSLPAGAIEPGEHPAEAVIREVREETGLLV-KPTRLLGVfggkefRYTYPNGDqv 95

                         90       100       110
                 ....*....|....*....|....*....|...
gi 504410385  80 ---VLLDVWEVLAFAGEPHGAEGQPLAWVAPEE 109
Cdd:cd04676   96 eytVIAFKCVVTGGTLNAIDGETSELRYFSRTQ 128

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: 467571 Cd Length: 145 Bit Score: 43.23 E-value: 3.15e-05

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 504410385  26 DKHQGGLWEFPGGKVEDGESVESALARELQEELGIEV 62
Cdd:cd04689   25 DFGKGTLIETAGGGVEENENLEEAIRRELKEELGVEV 61

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: 42.97 E-value: 3.71e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   7 AAAVIRGPESSVLIAKR---PLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQ-VLL 82
Cdd:cd04700   16 AGVVLLNERGDILLVQEkgiSGHPEKAGLWHIPSGAVEDGENPQDAAVREACEETGLRVRLVKFLGAYLGRFPDGVlVLR 95

                         90       100       110
                 ....*....|....*....|....*....|...
gi 504410385  83 DVWevlafAGEPhgAEGQPLAWVAPEELVDYSF 115
Cdd:cd04700   96 HVW-----LAEP--EPGQVLAPAFTDEIAEASF 121

ADP-ribose pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase) (also known as 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.

Pssm-ID: 467598 [Multi-domain] Cd Length: 149 Bit Score: 42.85 E-value: 3.92e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 504410385   9 AVIRGPESS---VLIAK-R-PLDKHqggLWEFPGGKVEDGESVESALARELQEELG 59
Cdd:cd18888    9 AILKRKLKPpelVLVKQyRpPVNAY---TIEFPAGLVDPGESPEQAALRELKEETG 61

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

Pssm-ID: 467548 [Multi-domain] Cd Length: 132 Bit Score: 42.28 E-value: 5.10e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   6 VAAAVIRGPESSVLIAKRPLDKHQGglWEFPGGKVEDGESVESALARELQEELGIEVTQA 65
Cdd:cd04663    3 VCAYVTRGRNRELLVFEHPDFPEAG--LQVPKGTVEPGESPEEAALRELAEETGLTGARV 60

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: 42.61 E-value: 5.31e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  10 VIRGPESSVLIAKRpLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQ-PLIQV-RHDYPD 77
Cdd:cd03430   21 IIRNEDGEILLGKR-NNRPAQGYWFVPGGRILKNETLDDAFKRIAREELGLEVTINAaEFLGVyEHFYDD 89

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: 42.16 E-value: 7.05e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 504410385  18 VLIAKRPLDK-HQGGLWEFP-GGKVEDGESVESALARELQEELGIEVTQAQ 66
Cdd:cd04692   41 LLLQKRSANKdDFPGLWDISaAGHIDAGETYEEAAVRELEEELGLTVSPED 91

Mitochondrial ribosomal protein L46; Mitochondrial ribosomal protein L46 (MRP L46) is a component of the large subunit (39S) of the mammalian mitochondrial ribosome and a member of the NUDIX hydrolase superfamily. MRPs are thought to be involved in the maintenance of the mitochondrial DNA. In general, members of the NUDIX hydrolase superfamily require 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), which functions as a metal binding and catalytic site. MRP L46 appears to contain a modified NUDIX motif.

Pssm-ID: 467546 Cd Length: 142 Bit Score: 41.83 E-value: 8.15e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   3 RIHVAAAVIRGPESS----------------VLIAKrplDKHQGGLWEFPGGKVEDGESVESALARELQEELGIE----- 61
Cdd:cd04661    1 RISAAVILSRLPEADekndrkslerkldrtlYLLVK---QKKGKGPWQFPQGDVEEGETLREAAERGLRELGGDNmntwf 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 504410385  62 VTQAqPLIQVRHDYPDKqvlldVWEVLA----FAGEPHGAEGQPL---AWVAPEELVDYSFP 116
Cdd:cd04661   78 VGNA-PIGVYKYKYPKK-----TKEFGYksffLKGRFMPGQKKGVsdfAWLTKEELKEYVDP 133

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: 467558 [Multi-domain] Cd Length: 118 Bit Score: 40.91 E-value: 1.30e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  31 GLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQVLldvweVLAFAGEPHGAEGQPLA------- 103
Cdd:cd04674   29 GELALPGGYIEYGETWQEAAVRELREETGVEADAAEVRLFAVRSAPDGTLL-----IFGLLPERPVADLPPFAptdeate 103

                         90
                 ....*....|...
gi 504410385 104 WVAPEELVDYSFP 116
Cdd:cd04674  104 WVVLTEPVELAFP 116

NUDIX family Ndx2; NUDIX family protein Ndx2 found in Thermus thermophilus has ADP-ribose pyrophosphatase (ADPRase) as well as flavin adenine dinucleotide (FAD) activity. 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.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: 467609 [Multi-domain] Cd Length: 137 Bit Score: 41.00 E-value: 1.45e-04

                         10        20
                 ....*....|....*....|....*....
gi 504410385  33 WEFPGGKVEDGESVESALARELQEELGIE 61
Cdd:cd24161   32 WEIPAGGWPEGEDPEEAARRELREETGLR 60

NUDIX domain family NudE found in Escherichia coli, and similar proteins; The adenosine nucleotide hydrolase NudE protein in Escherichia coli is a NUDIX hydrolase family member active against ADP ribose, NADH, AP2A and AP3A33, and is classified as a hydrolase (E.C. 3.6.1.-) based on gene annotations. It is an 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. 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: 467604 [Multi-domain] Cd Length: 134 Bit Score: 40.69 E-value: 1.94e-04

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 504410385  35 FPGGKVEDGESVESALARELQEELGIEVTQAQPLIQV 71
Cdd:cd24156   33 FPKGLIDPGETPEEAANRELKEEIGFGARQLTLLREL 69

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

Pssm-ID: 467555 [Multi-domain] Cd Length: 130 Bit Score: 40.37 E-value: 2.01e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   5 HVAAAVIRGPESSVLI---AKRPLdkhqGGLWEFPGGKVEDGESVESALARELQEELGIE 61
Cdd:cd04671    1 YVVAAVIINEQGEVLMiqeAKRSC----RGKWYLPAGRVEPGESIVEAAKREVKEETGLK 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: 467545 [Multi-domain] Cd Length: 123 Bit Score: 40.25 E-value: 2.15e-04

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 504410385  31 GLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPL 68
Cdd:cd04511   27 GYWTLPAGFMELGETTEQGAARETREEAGARVEIGSLY 64

nudix hydrolase

Pssm-ID: 215184 [Multi-domain] Cd Length: 144 Bit Score: 40.61 E-value: 2.48e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 504410385   3 RIHVAAAVIRGpeSSVLIAKRpLDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPL 68
Cdd:PLN02325   9 RVAVVVFLLKG--NSVLLGRR-RSSIGDSTFALPGGHLEFGESFEECAAREVKEETGLEIEKIELL 71

NAD(+) diphosphatase;

Pssm-ID: 234699 [Multi-domain] Cd Length: 256 Bit Score: 41.76 E-value: 2.70e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 504410385   9 AVIRGPEssVLIAKRPldKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVT 63
Cdd:PRK00241 138 AVRRGDE--ILLARHP--RHRNGVYTVLAGFVEVGETLEQCVAREVMEESGIKVK 188

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: 40.17 E-value: 4.77e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385  18 VLIAKRPLDK-HQGGLWE-------FPGgkvedgESVESALARELQEELGIEVTQAQPLIQVRHDYPDKQVLLDvWE--- 86
Cdd:cd02885   42 LLLQRRALSKyTWPGLWTntccshpLPG------EGVEDAAQRRLREELGIPVCDLEELPRFRYRATDDNGLVE-HEidh 114

                         90       100       110
                 ....*....|....*....|....*....|
gi 504410385  87 VLA--FAGEPHG--AEGQPLAWVAPEELVD 112
Cdd:cd02885  115 VFVgrADGDPVPnpEEVSDYRWVSLEELRE 144

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 41.15 E-value: 5.02e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 504410385  31 GLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLIQVR----HDYPDK 78
Cdd:PRK05379 228 GLWALPGGFLEQDETLLDACLRELREETGLKLPEPVLRGSIRdqqvFDHPGR 279

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: 467599 [Multi-domain] Cd Length: 127 Bit Score: 39.13 E-value: 6.49e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 504410385  25 LDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTqAQPLIQVrHDY 75
Cdd:cd18889   17 LVQEKDGRWSLPGGWVDVNQSIKENTIKEAKEEAGLDVE-PKRIIAV-LDR 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: 467590 [Multi-domain] Cd Length: 142 Bit Score: 39.10 E-value: 7.87e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   9 AVIRGPESSVLIAKRPLDkhqgGLWEFPGGKVEDGESVESALARELQEELGIEVtQAQPLIQVRHD----YP--DKQVLL 82
Cdd:cd18879   23 AVVLRDAGRVLLVRRADN----GRWTPVTGIVEPGEQPADAAVREVLEETGVDV-EVERLASVGASppvtYPngDQCQYL 97

                         90       100       110
                 ....*....|....*....|....*....|
gi 504410385  83 DvwevLAFAGEPHGAEgqplAWVAPEELVD 112
Cdd:cd18879   98 D----LTFRCRPVGGE----ARVNDDESLE 119

mRNA decapping enzyme 2; mRNA decapping enzyme 2 (Dcp2p; EC 3.6.1.62), nucleoside diphosphate linked moiety X))-type motif 20/Nudt20, is required for degradation of mRNAs, both in normal mRNA turnover, and in nonsense-mediated mRNA decay (NMD). Its catalytic subunit, and Dcp1p are the two components of the decapping enzyme complex. Decapping is a key step in both general and nonsense-mediated 5'->3' mRNA-decay pathways. Dcp2p contains an all-alpha helical N-terminal domain and a C-terminal domain which has the NUDIX fold. While decapping is not dependent on the N-terminus of Dcp2p, it does affect its efficiency. Dcp1p binds the N-terminal domain of Dcp2p stimulating the decapping activity of Dcp2p. Decapping permits the degradation of the transcript and is a site of numerous control inputs. It is responsible for nonsense-mediated decay as well as AU-rich element (ARE)-mediated decay. In addition, it may also play a role in the levels of mRNA. Enzymes belonging to the NUDIX hydrolase superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V).

Pssm-ID: 467540 Cd Length: 144 Bit Score: 39.07 E-value: 8.27e-04

                         10        20        30
                 ....*....|....*....|....*....|.
gi 504410385  33 WEFPGGKVEDGESVESALARELQEELGIEVT 63
Cdd:cd03672   28 WGFPKGKINKDESDADCAIREVYEETGFDIS 58

dihydroneopterin triphosphate pyrophosphatase; Provisional

Pssm-ID: 236516 [Multi-domain] Cd Length: 148 Bit Score: 38.72 E-value: 1.02e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 504410385  10 VIRGPESSVLIAKRpldKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQ 66
Cdd:PRK09438  13 VIYTPDLGVLMLQR---ADDPDFWQSVTGSLEEGETPAQTAIREVKEETGIDVLAEQ 66

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

Pssm-ID: 467603 [Multi-domain] Cd Length: 187 Bit Score: 39.05 E-value: 1.15e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 504410385  25 LDKHQGGLWEFPGGKVEDGESVESALARELQEELGIEVTQAQPL 68
Cdd:cd24155   70 ARDESPWLLEIVAGMIDAGETPEDVARREAEEEAGLTLDALEPI 113

ADP-ribose pyrophosphatase NudF; Provisional

Pssm-ID: 182682 [Multi-domain] Cd Length: 202 Bit Score: 39.33 E-value: 1.32e-03

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 504410385  32 LWEFPGGKVEDGESVESALARELQEELGIEVTQAQPLI 69
Cdd:PRK10729  83 LLEMVAGMIEEGESVEDVARREAIEEAGLIVGRTKPVL 120

CDP-Choline Pyrophosphatase and similar proteins; Members include: CDP-Choline Pyrophosphatase, ADP-ribose pyrophosphatase, and UDP-X diphosphatase. CDP-choline pyrophosphatase catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. ADP-ribose pyrophosphatase catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. UDP-X diphosphatase hydrolyzes UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-alanine. 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: 467556 [Multi-domain] Cd Length: 128 Bit Score: 37.54 E-value: 2.02e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504410385   4 IHVAAAVIRgpESSVLIAKRPLDkhqgGLWEFPGGKVEDGESVESALARELQEELGIEVTqAQPLIQVRH 73
Cdd:cd04672    3 VDVRAAVFK--DGKILLVREKSD----GRWTLPGGWADVGLSPAENAVKEVREESGYEVR-ARKLLAVFD 65

adenosine nucleotide hydrolase NudE; Provisional

Pssm-ID: 183303 Cd Length: 185 Bit Score: 37.48 E-value: 4.14e-03

                         10        20
                 ....*....|....*....|....*
gi 504410385  35 FPGGKVEDGESVESALARELQEELG 59
Cdd:PRK11762  78 FPKGLIDPGETPLEAANRELKEEVG 102