NCBI Conserved Domain Search

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 543.06 E-value: 0e+00

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B         2 AMDPMYDISVFIGRFQPFHKGHLHNIIIALQNSKKVIINIGSCFNTPNIKNPFSFEQRKQMIESDLQvaGIDLDTVVIEP 81
Cdd:PRK05379   1 PMNRRYDYLVFIGRFQPFHNGHLAVIREALSRAKKVIVLIGSADLARSIKNPFSFEERAQMIRAALA--GIDLARVTIRP 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B        82 LADYFYQEQKWQDELRKNVYKHAKNNNSIAIVGHIKDSSSYYIRSFPEWDYIGVDNYKNFNATEFRQKFYNGIISKQYMC 161
Cdd:PRK05379  79 LRDSLYNDSLWLAEVQAAVAEHAGADARIGLIGHEKDASSYYLRSFPQWELVDVPNTEDLSATEIRDAYFEGRISSFYGW 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B       162 snDPKLGTYNFLTKFMDTQVYQDLVAENNYVIEYKRLWLKAPFKPNFVTVDALVIVNDHILMVQRKAHPGKDLWALPGGF 241
Cdd:PRK05379 159 --AVPAPVYAFLEAFRQTPAYAQLVAEADFIEQYRKAWAAAPYPPTFVTVDAVVVQSGHVLLVRRRAEPGKGLWALPGGF 236

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B       242 LECDETIAQAIIRELFEETNINLTHEQLAIAKRCEKVFDYPDRSVRGRTISHVGLFVFDQWPsLPEINAADDAKDVKWIS 321
Cdd:PRK05379 237 LEQDETLLDACLRELREETGLKLPEPVLRGSIRDQQVFDHPGRSLRGRTITHAFLFEFPAGE-LPRVKGGDDADKARWVP 315

                        330       340
                 ....*....|....*....|....*.
2QJT_B       322 LgSNIKNICDRMLEDHYQIITILLEE 347
Cdd:PRK05379 316 L-AELLAMRDRMFEDHFQIITHFLGR 340

Nicotinamide/nicotinate mononucleotide adenylyltransferase of bifunctional proteins, also containing a Nudix hydrolase domain; N-terminal NMNAT (Nicotinamide/nicotinate mononucleotide adenylyltransferase) domain of a novel bifunctional enzyme endowed with NMN adenylyltransferase and Nudix hydrolase activities. This domain is highly homologous to the archeal NMN adenyltransferase that catalyzes NAD synthesis from NMN and ATP. NMNAT is an essential enzyme in the biosynthesis of NAD(+) and NADP(+). Nicotinamide-nucleotide adenylyltransferase synthesizes NAD via the salvage pathway, while nicotinate-nucleotide adenylyltransferase synthesizes the immediate precursor of NAD via the de novo pathway. The C-terminal domain of this enzyme shares homology with the archaeal ADP-ribose pyrophosphatase, a member of the 'Nudix' hydrolase family.

Pssm-ID: 173919 Cd Length: 181 Bit Score: 317.01 E-value: 1.82e-109

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B        9 ISVFIGRFQPFHKGHLHNIIIALQNSKKVIINIGSCFNTPNIKNPFSFEQRKQMIESDLQVAGIDLDTVVIEPLADYFYQ 88
Cdd:cd02168   1 YLVYIGRFQPFHNGHLAVVLIALEKAKKVIILIGSARTARNIKNPWTSEEREVMIEAALSDAGADLARVHFRPLRDHLYS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B       89 EQKWQDELRKNVYKHAKNNNSIAIVGHIKDSSSYYIRSFPEWDYIGVDNYKNFNATEFRQKFYNGiisKQYMCSNDPKLG 168
Cdd:cd02168  81 DNLWLAEVQQQVLEIAGGSASVGLVGHRKDASSYYLRSFPQWDYLEVPNYPDLNATDIRRAYFEG---KEAMYRAALPAG 157

                       170       180
                ....*....|....*....|....
2QJT_B      169 TYNFLTKFMDTQVYQDLVAENNYV 192
Cdd:cd02168 158 VYDFLTAFQDTPRYAQLVAEYRAI 181

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: 139.60 E-value: 8.68e-41

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      208 FVTVDALVIVND----HILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTH-EQLaiakrceKVFDYP 282
Cdd:cd18873   2 SVTVDCVIFGFDdgelKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETGLKDIYlEQL-------GTFGDP 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
2QJT_B      283 DRSVRGRTISHVGLFVFDQWPslPEINAADDAKDVKWISLGSNIknicDRMLEDHYQIITILLE 346
Cdd:cd18873  75 DRDPRGRVISVAYLALVPEED--LAPKAGDDAAEARWFPVDELL----PPLAFDHAEIIADALE 132

nicotinate-nicotinamide nucleotide adenylyltransferase;

Pssm-ID: 184329 Cd Length: 196 Bit Score: 135.89 E-value: 1.79e-38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B         7 YDISVFIGRFQPFHKGHLHNIIIALQNSKKVIINIGSCFNTPNIKNPFSFEQRKQMIESDLQVAgiDLDTVVIEPLADyF 86
Cdd:PRK13793   4 FDYLVFIGRFQPFHLAHMQTIEIALQQSRYVILALGSAQMERNIKNPFLAIEREQMILSNFSLD--EQKRIRFVHVVD-V 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B        87 YQEQKWQDELRKNVYKHAKNNNSIAIVGHIKDSSSYYIRSFPEWDYIGVDNYKN-FNATEFRQKFYNGIISKQYMcsndP 165
Cdd:PRK13793  81 YNDEKWVKQVKSLVNGVIEPNSKVGLIGHFKDESSYYLRLFPEWVMVELDSLKDsISATPMREAYYQGKIKTDAF----P 156

                        170       180
                 ....*....|....*....|
2QJT_B       166 KlGTYNFLTKFMDTQVYQDL 185
Cdd:PRK13793 157 K-GTIQFLEEFQNTPLYLQL 175

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 102.36 E-value: 1.17e-26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      208 FVTVDALVI-VNDHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLAiakrceKVFDYPDrsv 286
Cdd:COG1051   6 KVAVDAVIFrKDGRVLLVRRADEPGKGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELL------GVFDHPD--- 76

                        90       100       110
                ....*....|....*....|....*....|....*.
2QJT_B      287 RGRTISHVglFVFDQWPslPEINAADDAKDVKWISL 322
Cdd:COG1051  77 RGHVVSVA--FLAEVLS--GEPRADDEIDEARWFPL 108

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: 92.58 E-value: 5.17e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      209 VTVDALVIVNDHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLAiakrceKVFDYPDRSVRG 288
Cdd:cd04673   2 VAVGAVVFRDGRVLLVRRGNPPDAGLWSFPGGKVELGETLEDAALRELREETGLEAEVVGLL------TVVDVIERDEAG 75

                        90       100       110
                ....*....|....*....|....*....|....*
2QJT_B      289 RTISH-VGLFVFDQWPSlPEINAADDAKDVKWISL 322
Cdd:cd04673  76 RVRFHyVILDFLAEWVS-GEPVAGDDALDARWFSL 109

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: 90.54 E-value: 2.00e-22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      209 VTVDALVIVN-DHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLAiakrceKVFDYPDRSVR 287
Cdd:cd02883   1 VAVGAVVFDDeGRVLLVRRSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLL------GVYEFPDPDEG 74

                        90       100       110
                ....*....|....*....|....*....|....
2QJT_B      288 GRTISHVglFVFDQWPSLPEINAADDAKDVKWIS 321
Cdd:cd02883  75 RHVVVLV--FLARVVGGEPPPLDDEEISEVRWVP 106

Nicotinamide mononucleotide adenylyltransferase [Coenzyme transport and metabolism]; Nicotinamide mononucleotide adenylyltransferase is part of the Pathway/BioSystem: NAD biosynthesis

Pssm-ID: 440676 [Multi-domain] Cd Length: 162 Bit Score: 91.80 E-value: 2.91e-22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B        6 MYDISVFIGRFQPFHKGHLHNIIIALQNSKKVIINIGSCfNTP-NIKNPFSFEQRKQMIESDLqvAGIDLDTVVIEPLAD 84
Cdd:COG1056   1 MMKRGLFIGRFQPFHLGHLAVIKWALEEVDELIIGIGSA-QEShTPRNPFTAGERIEMIRAAL--KEEGLSRVYIVPIPD 77

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
2QJT_B       85 yFYQEQKWqdelRKNVYKHAKN------NNSiaIVGHIKDSSSYYIRSFPEWdyigvdNYKNFNATEFRQKFYNG 153
Cdd:COG1056  78 -INNNSLW----VSHVKSLVPPfdvvysNNP--LVGRLFKEAGYEVLLPPLF------EREEYSGTEIRRLMLEG 139

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 83.30 E-value: 1.74e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B        206 PNFVTVDALVIVND-HILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNInlTHEQLAIAKRCEKVFDYPDR 284
Cdd:pfam00293   1 KRRVAVGVVLLNEKgRVLLVRRSKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGL--EPELLELLGSLHYLAPFDGR 78

                          90       100       110
                  ....*....|....*....|....*....|....*...
2QJT_B        285 SVRGRTISHVglfVFDQWPSLPEINAADDAKDVKWISL 322
Cdd:pfam00293  79 FPDEHEILYV---FLAEVEGELEPDPDGEVEEVRWVPL 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: 467564 [Multi-domain] Cd Length: 135 Bit Score: 71.06 E-value: 4.79e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      211 VDALVIVNDHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLaiakrcekVFDYPDRSV-RGR 289
Cdd:cd04681   9 VGVIIRNEGEILFVRRAKEPGKGKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRY--------LCSLPNTYLyKGI 80

                        90       100       110
                ....*....|....*....|....*....|....
2QJT_B      290 TISHVGLFVFDQWPSLPEINAA-DDAKDVKWISL 322
Cdd:cd04681  81 TYKTCDLFFTAELDEKPKLKKAeDEVAELEWLDL 114

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: 69.25 E-value: 1.78e-14

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
2QJT_B      209 VTVDALVIVNDHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNInLTHEQLAIAKRC 275
Cdd:cd04691   2 LGVGGVVVKEGKVLLVKRAYGPGKGRWTLPGGFVEEGETLDEAIVREVLEETGI-DAKPVGIIGVRS 67

Nicotinamide/nicotinate mononucleotide adenylyltransferase, archaeal; This family of archaeal proteins exhibits nicotinamide-nucleotide adenylyltransferase (NMNAT) activity utilizing the salvage pathway to synthesize NAD. In some cases, the enzyme was tested and found also to have the activity of nicotinate-nucleotide adenylyltransferase an enzyme of NAD de novo biosynthesis, although with a higher Km. In some archaeal species, a number of proteins which are uncharacterized with respect to activity, are also present.

Pssm-ID: 173917 Cd Length: 163 Bit Score: 70.02 E-value: 2.35e-14

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
2QJT_B       11 VFIGRFQPFHKGHLHNIIIALQNSKKVIINIGSCFNTPNIKNPFSFEQRKQMIESDLQVAGIDLDTVVIEPLADYFY 87
Cdd:cd02166   3 LFIGRFQPFHLGHLKVIKWILEEVDELIIGIGSAQESHTLENPFTAGERVLMIRRALEEEGIDLSRYYIIPVPDIER 79

nicotinamide-nucleotide adenylyltransferase; Provisional

Pssm-ID: 179235 Cd Length: 174 Bit Score: 68.36 E-value: 9.28e-14

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
2QJT_B        12 FIGRFQPFHKGHLHNIIIALQNSKKVIINIGSCFNTPNIKNPFSFEQRKQMIESDLQVAGIDLDTVVIEPLAD 84
Cdd:PRK01153   5 FIGRFQPFHKGHLEVIKWILEEVDELIIGIGSAQESHTLKNPFTAGERILMIRKALEEEGIDLSRYYIIPIPD 77

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: 66.98 E-value: 1.79e-13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      213 ALVIVND--HILMVQRKAHP-GKDLWALPGGFLECDETIAQAIIRELFEETNINltheqlaiAKRCEKVFDYPDRSVRGR 289
Cdd:COG0494  17 VVVLLDDdgRVLLVRRYRYGvGPGLWEFPGGKIEPGESPEEAALRELREETGLT--------AEDLELLGELPSPGYTDE 88

                        90       100       110
                ....*....|....*....|....*....|....*
2QJT_B      290 TIsHVglFVFDQWPSLPEINAADDA--KDVKWISL 322
Cdd:COG0494  89 KV-HV--FLARGLGPGEEVGLDDEDefIEVRWVPL 120

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: 64.78 E-value: 5.45e-13

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
2QJT_B      215 VIVND-HILMVQR---KAHPGkdLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLaiakRCEKVFDYPDRSVR 287
Cdd:cd03425   7 IIVDDgRVLIAQRpegKHLAG--LWEFPGGKVEPGETPEQALVRELREELGIEVEVGEP----LGTVEHDYPDFHVR 77

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: 64.86 E-value: 5.72e-13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      213 ALVIVNDHILMVqRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLAIakrcekVFDYPDRSVRGRTIS 292
Cdd:cd18880   6 AIIIEDGKLLLV-KHRDEGGIFYILPGGGQEHGETLPEALKRECLEETGLDVEVGDLLF------VREYIGPNKPVHQVE 78

                        90       100       110
                ....*....|....*....|....*....|..
2QJT_B      293 HVglFVFDQWPSLPEINAADDA--KDVKWISL 322
Cdd:cd18880  79 LF--FLCTLEGGELTLGSDPDLnqVGVEWIPL 108

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: 64.51 E-value: 8.35e-13

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
2QJT_B      213 ALVIVND--HILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLT 265
Cdd:cd04678   6 GVIVLNDdgKVLLGRRKGSHGAGTWALPGGHLEFGESFEECAAREVLEETGLEIR 60

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: 63.64 E-value: 1.45e-12

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
2QJT_B      209 VTVdALVIVNDHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNI 262
Cdd:cd04674   6 VVV-ALLPVRDGLLVIRRGIEPGHGELALPGGYIEYGETWQEAAVRELREETGV 58

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: 63.41 E-value: 3.08e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      214 LVIVN-DHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLaiakRCEKVFDYPDRSVRGrtis 292
Cdd:cd18886   5 CFIIRdDEVLLLNRNKKPNMGKWNGVGGKLEPGESPEECAIREVFEETGLELEDLQL----RGIVTFPSFDGGEDW---- 76


                ....*..
2QJT_B      293 hvGLFVF 299
Cdd:cd18886  77 --LMYVF 81

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 65.28 E-value: 7.01e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B       209 VTVDALVI--VNDHILMVQRKAH---PGkdLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLAIakrcEKVFDYPD 283
Cdd:PRK08999   5 IHVAAGVIrdADGRILLARRPEGkhqGG--LWEFPGGKVEPGETVEQALARELQEELGIEVTAARPLI----TVRHDYPD 78


                 ....
2QJT_B       284 RSVR 287
Cdd:PRK08999  79 KRVR 82

Uncharacterized conserved protein [Function unknown];

Pssm-ID: 443287 [Multi-domain] Cd Length: 170 Bit Score: 62.88 E-value: 7.80e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      236 ALPGGFLECDETIAQAIIRELFEETNINLTH-EQLAiakrcekVFDYPDRSVRGRTIShVGLFvfdqwpSL--PEINAAD 312
Cdd:COG4111   1 ALPGGFVREHESLEDAARRWLAEQTGLELGYlEQLY-------TFGDPDRDPRGRVIS-VAYL------ALvrEEELRAD 66

                        90       100
                ....*....|....*....|....*....
2QJT_B      313 DAKDVKWIslgsNIKNIcDRMLEDHYQII 341
Cdd:COG4111  67 DADDAAWF----PVDEL-PPLAFDHRRIL 90

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: 61.81 E-value: 8.02e-12

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
2QJT_B      209 VTVDALVIVNDHILMVQRKAhpgKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLA 270
Cdd:cd04672   3 VDVRAAVFKDGKILLVREKS---DGRWTLPGGWADVGLSPAENAVKEVREESGYEVRARKLL 61

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: 61.01 E-value: 1.80e-11

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
2QJT_B      208 FVTVDALVIvNDH--ILMVQRKaHPGKDLWALPGGFLECDETIAQAIIRELFEETNIN 263
Cdd:cd04670   2 QVGVGGLVI-NENneVLVVQEK-YGGPGGWKLPGGLVDPGEDIGEAAVREVFEETGID 57

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

Pssm-ID: 467563 [Multi-domain] Cd Length: 121 Bit Score: 58.80 E-value: 7.14e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      211 VDALVIVND-HILMVQRKAHPGkdlWALPGGFLECDETIAQAIIRELFEETNINLTHEQLAIAkrcekVFDYPDRSVRgr 289
Cdd:cd04680   3 VRAIVLDDAgRVLLVRHTYVPG---WYLPGGGVDKGETAEEAARRELREEAGVVLTGPPRLFG-----VYFNRRVSPR-- 72

                        90       100       110
                ....*....|....*....|....*....|....*
2QJT_B      290 tiSHVGLFVFDQWPSLPEINAADDAKDVKWISLGS 324
Cdd:cd04680  73 --DHVALYRVREFEQTEPPEPNGEIAEAGFFALDA 105

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: 57.17 E-value: 4.05e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      213 ALVIVNDHILMVQrkaHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQL-AIAkrcEKVFDYPDRSVrgrti 291
Cdd:cd04688   7 AIIIRDGKVLLAR---GEDDDYYRLPGGRVEFGETSEDALVREFKEELGVEVEVVRLlFVV---ENFFTYDGKPF----- 75


                ....*....
2QJT_B      292 sHVGLFVFD 300
Cdd:cd04688  76 -HEIGFYYL 83

nicotinamide-nucleotide adenylyltransferase; This model describes a family of archaeal proteins with the activity of the NAD salvage biosynthesis enzyme nicotinamide-nucleotide adenylyltransferase (EC 2.7.7.1). In some cases, the enzyme was tested and found also to have the activity of nicotinate-nucleotide adenylyltransferase (EC 2.7.7.18), an enzyme of NAD de novo biosynthesis, although with a higher Km. In some archaeal species, a lower-scoring paralog, uncharacterized with respect to activity, is also present. These score between trusted and noise cutoffs. [Biosynthesis of cofactors, prosthetic groups, and carriers, Pyridine nucleotides]

Pssm-ID: 273671 Cd Length: 165 Bit Score: 57.90 E-value: 4.69e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B         12 FIGRFQPFHKGHLHNIIIALQNSKKVIINIGSCFNTPNIKNPFSFEQRKQMIESDLQvaGIDLDTVVIEPLADyFYQEQK 91
Cdd:TIGR01527   4 YIGRFQPFHLGHLEVIKKIAEEVDELIIGIGSAQESHTLENPFTAGERILMITQSLK--EVGDLTYYIIPIED-IERNSI 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
2QJT_B         92 WQDELRKNVYKH--AKNNNSIAIVghIKDSSSYYIRSFPEWdyigvdNYKNFNATEFRQKFYNG 153
Cdd:TIGR01527  81 WVSYVESMTPPFdvVYSNNPLVRR--LFKEAGYEVKRPPMF------NRKEYSGTEIRRRMLNG 136

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: 56.50 E-value: 6.07e-10

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
2QJT_B      209 VTVDALVIVNDH--ILMVQRK-----AHPGKdlWALPGGFLECDETIAQAIIRELFEETNINLTHEQL 269
Cdd:cd18882   1 HEVAIAILYDDRgkVLLQLRDdkpgiPYPGY--WGLFGGHLEPGETPEEAIRRELEEEIGYEPGEFRF 66

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: 56.52 E-value: 6.11e-10

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
2QJT_B      208 FVTVDALVIVND-HILMVqrKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLAIAKrcEKVFD 280
Cdd:cd18874   2 EPTVGALIFNPDgKVLLV--RSHKWNDLYGIPGGKVEWGETLEEALKREVKEETGLDITDIRFILVQ--ESINS 71

8-oxo-dGTP diphosphatase MutT;

Pssm-ID: 182721 [Multi-domain] Cd Length: 129 Bit Score: 56.53 E-value: 6.70e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B       218 NDHILMVQRKA--HPGkDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLAiakrcEKV-FDYPDRsvrgrtisHV 294
Cdd:PRK10776  15 NNEIFITRRAAdaHMA-GKWEFPGGKIEAGETPEQALIRELQEEVGITVQHATLF-----EKLeYEFPDR--------HI 80

                         90
                 ....*....|
2QJT_B       295 GLFVF--DQW 302
Cdd:PRK10776  81 TLWFWlvESW 90

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: 56.39 E-value: 6.80e-10

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
2QJT_B      209 VTVDALVIVNDHILMVqRKAhpGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQL 269
Cdd:cd04690   2 VKAAVIIIKDGRLLLV-RKR--GTDAFYLPGGKREPGETPLQALVRELKEELGLDLDPDSL 59

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: 56.09 E-value: 7.29e-10

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
2QJT_B      209 VTVDALVIVNDHILMVQR-KAHPGKdlWALPGGFLECDETIAQAIIRELFEETNINLTHEQLA 270
Cdd:cd04699   3 VSVKGVIFDNGRVLLLRRsRAGAGE--WELPGGRLEPGESPEEALKREVKEETGLDVSVGELL 63

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

Pssm-ID: 467562 [Multi-domain] Cd Length: 126 Bit Score: 55.78 E-value: 9.44e-10

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
2QJT_B      209 VTVDALVIVNDHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQL 269
Cdd:cd04679   3 VGCGAAILDDGRLLLVLRLRAPEAGHWGLPGGKVDWLETVEDAVRREILEELGLEIELTRL 63

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

Pssm-ID: 467560 [Multi-domain] Cd Length: 137 Bit Score: 55.60 E-value: 1.34e-09

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
2QJT_B      215 VIVNDH--ILMVQRKahpGKDLWALPGGFLECDETIAQAIIRELFEETNINL 264
Cdd:cd04677  18 IILNEQgrILLQKRT---DTGDWGLPGGAMELGESLEETARREVFEETGLTV 66

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: 55.66 E-value: 1.47e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      214 LVIVN--DHILMVQrkAH----PGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLA--IAKRCEkVFDYPDRS 285
Cdd:cd04685   5 VLLLDpdGRVLLFR--FHdpddPGRSWWFTPGGGVEPGESPEQAAVRELREETGLRLEPDDLGgpVWRRRA-VFDFSGET 81


                ....
2QJT_B      286 VRGR 289
Cdd:cd04685  82 VRQD 85

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: 53.83 E-value: 4.44e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      213 ALVIV--NDHILMVQRKahpgKDLWALPGGFLECDETIAQAIIRELFEETNINltheqlaiAKRCEKVFDYPDRSVRgrt 290
Cdd:cd04667   3 ATVICrrGDRILLVARR----GGRWLLPGGKIEPGESPLEAAIRELKEETGLA--------ALSLLYLFEHEGPHKL--- 67

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
2QJT_B      291 isHvglFVFD-QWPSLPEINAADDAKDVKWISLGS----NIKNICDRMLEDHYQ 339
Cdd:cd04667  68 --H---HVFLaEAPDGGRPRPGNEIARCRWVSADQlrdlNLSRATRLIVRRYLR 116

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: 53.28 E-value: 8.88e-09

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      206 PNFVTVdaLVIVND-HILMVQ--RKAhPGKDLWALPGGFLECDETIAQAIIRELFEETNI 262
Cdd:cd03424   2 PGAVAV--LAITDDgKVVLVRqyRHP-VGRVLLELPAGKIDPGEDPEEAARRELEEETGY 58

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: 53.03 E-value: 9.56e-09

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
2QJT_B      209 VTVDALVIVND--HILMVQrkaHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLT 265
Cdd:cd03674   2 FTASAFVVNPDrgKVLLVH---HRKLGRWLQPGGHVEPDEDPLEAALREAREETGLDVE 57

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

Pssm-ID: 467545 [Multi-domain] Cd Length: 123 Bit Score: 52.96 E-value: 1.06e-08

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
2QJT_B      209 VTVDALVIVNDHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETN 261
Cdd:cd04511   3 IVVGCLPEWEGKVLLCRRAIEPRKGYWTLPAGFMELGETTEQGAARETREEAG 55

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: 52.25 E-value: 1.69e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      213 ALVIV--NDHILMVQrkaHPGKDLWALPGGFLECDETIAQAIIRELFEETNinltheqlAIAKRCEKVFDYpdrSVRGRT 290
Cdd:cd04665   3 VVVIAryKGKWLFTR---HKERRGWEFPGGKREPGETIEEAARRELYEETG--------AVIFELKPLGQY---SVHGKG 68


                ....*
2QJT_B      291 ISHVG 295
Cdd:cd04665  69 QEFFG 73

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: 4.14e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      203 PFKPNfvtVdALVIVND--HILMVQRKAHPGKdlWALPGGFLECDETIAQAIIRELFEETNINLTHEQLaIAKRCEKV-F 279
Cdd:cd03671   1 PYRPN---V-GIVLFNRdgQVLVGRRIDVPGA--WQFPQGGIDEGEDPEEAALRELYEETGLSPEDVEI-IAETPDWLtY 73

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      280 DYPDRSV-RGRTISHVG----LFVFdQWPSL-PEINAADDAK----DVKWISLGSNIKNI 329
Cdd:cd03671  74 DLPEDLIrKGWGGKYRGqkqkWFLF-RFTGDdSEINLDTHEHpefdAWRWVDLEELPDLV 132

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

Pssm-ID: 182536 [Multi-domain] Cd Length: 135 Bit Score: 50.90 E-value: 5.73e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
2QJT_B       211 VDALVIVNDHILMVQRKAH---PGkdLWALPGGFLECDETIAQAIIRELFEETNI 262
Cdd:PRK10546   7 VAAIIERDGKILLAQRPAHsdqAG--LWEFAGGKVEPGESQPQALIRELREELGI 59

Cytidylyltransferase-like; This family includes: Cholinephosphate cytidylyltransferase; glycerol-3-phosphate cytidylyltransferase. It also includes putative adenylyltransferases, and FAD synthases.

Pssm-ID: 396172 [Multi-domain] Cd Length: 134 Bit Score: 50.40 E-value: 9.68e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B         11 VFIGRFQPFHKGHLHNIIIALQN-SKKVIINIGSC-FNTPNIKNPFSFEQRKQMIES---DLQVAGIDLDTVVIEPL--- 82
Cdd:pfam01467   1 LFGGTFDPIHLGHLRLLEQAKELfDEDLIVGVPSDePPHKLKRPLFSAEERLEMLELakwVDEVIVVAPWELTRELLkel 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
2QJT_B         83 -ADYF--------YQEQKWQDEL---------RKNVYKHAKNNNSIaivghikdSSSYYIR 125
Cdd:pfam01467  81 nPDVLvigadsllDFWYELDEILgnvklvvvvRPVFFIPLKPTNGI--------SSTDIRE 133

dihydroneopterin triphosphate pyrophosphatase; Provisional

Pssm-ID: 236516 [Multi-domain] Cd Length: 148 Bit Score: 50.66 E-value: 1.07e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
2QJT_B       211 VDALVIV---NDHILMVQRKAHPGkdLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLAI 271
Cdd:PRK09438   8 VSVLVVIytpDLGVLMLQRADDPD--FWQSVTGSLEEGETPAQTAIREVKEETGIDVLAEQLTL 69

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: 49.98 E-value: 1.28e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      211 VDALVIVNDHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTheqlaIAKRCEKVFDYPDRSVRGRT 290
Cdd:cd04686   4 VYGIIIRNDKLLLIRKTRGPYQGRYDLPGGSQEFGESLEDALKREFAEETGMTVT-----SYDNLGVYDFFVPWSDKELG 78

                        90       100       110
                ....*....|....*....|....*....|....*....
2QJT_B      291 -ISHVGLF----VFDQWPSLPEINAADDAKDVKWISLGS 324
Cdd:cd04686  79 dVHHIGVFydveLLDNNISELLQFEGQDSLGAVWIPLQD 117

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: 49.71 E-value: 1.97e-07

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
2QJT_B      213 ALVIVN-DHILMVQRKAhpGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQL 269
Cdd:cd04676  21 AAVILNeDGRILLQRKG--GLGLWSLPAGAIEPGEHPAEAVIREVREETGLLVKPTRL 76

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: 49.02 E-value: 2.33e-07

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
2QJT_B      215 VIV-----NDHILMVQRKAHPGKdLWALPGGFLECDETIAQAIIRELFEETNINLTH 266
Cdd:cd03429   4 VIVlvtngEDKILLARQPRWPPG-RYSLLAGFVEPGETLEEAVRREVKEEVGLRVKN 59

cytidyltransferase-like domain; Protein families that contain at least one copy of this domain include citrate lyase ligase, pantoate-beta-alanine ligase, glycerol-3-phosphate cytidyltransferase, ADP-heptose synthase, phosphocholine cytidylyltransferase, lipopolysaccharide core biosynthesis protein KdtB, the bifunctional protein NadR, and a number whose function is unknown. Many of these proteins are known to use CTP or ATP and release pyrophosphate.

Pssm-ID: 272920 [Multi-domain] Cd Length: 66 Bit Score: 47.30 E-value: 2.69e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
2QJT_B          9 ISVFIGRFQPFHKGHLHNIIIALQNSKKVIINIGSCFNTPNIKNP--FSFEQRKQMIES 65
Cdd:TIGR00125   1 RVIFVGTFDPFHLGHLDLLERAKELFDELIVGVGSDQFVNPLKGEpvFSLEERLEMLKA 59

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: 49.07 E-value: 2.71e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
2QJT_B      231 GKDLWALPGGFLECDETIAQAIIRELFEETNINltheqlaiAKRCEKV----FDYPDRSVrgRTISHVglFVFDQW 302
Cdd:cd03427  25 GAGKWNGFGGKVEPGETIEEAAVRELEEEAGLT--------ATELEKVgrlkFEFPDDPE--AMDVHV--FRADSW 88

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

Pssm-ID: 467549 [Multi-domain] Cd Length: 132 Bit Score: 48.79 E-value: 3.67e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      214 LVIV-----NDHILMVQRKAHPGkdLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLAiakRCEKVFDYPDRSVRG 288
Cdd:cd04664   4 LVVIyrkdeEGEVLLLKRTDDGG--FWQSVTGGIEDGETPWQAALRELKEETGLDPLELQLI---DLNVSNFYEIFDDWR 78

                        90
                ....*....|.
2QJT_B      289 RTISHVGLFVF 299
Cdd:cd04664  79 PGVTVNTEHVF 89

Cytidylyltransferase-like domain; Cytidylyltransferase-like domain. Many of these proteins are known to use CTP or ATP and release pyrophosphate. Protein families that contain at least one copy of this domain include citrate lyase ligase, pantoate-beta-alanine ligase, glycerol-3-phosphate cytidyltransferase, ADP-heptose synthase, phosphocholine cytidylyltransferase, lipopolysaccharide core biosynthesis protein KdtB, the bifunctional protein NadR, and a number whose function is unknown.

Pssm-ID: 185678 [Multi-domain] Cd Length: 143 Bit Score: 48.59 E-value: 4.32e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B        9 ISVFIGRFQPFHKGHLHNIIIALQNSKKVIInIGSCFNTP---NIKNPFSFEQRKQMIESDLQvagidlDTVVIEPLADY 85
Cdd:cd02039   1 VGIIIGRFEPFHLGHLKLIKEALEEALDEVI-IIIVSNPPkkkRNKDPFSLHERVEMLKEILK------DRLKVVPVDFP 73

                        90       100
                ....*....|....*....|....*....
2QJT_B       86 FYQEQKWQDELRKNVYKHaknNNSIAIVG 114
Cdd:cd02039  74 EVKILLAVVFILKILLKV---GPDKVVVG 99

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

Pssm-ID: 467543 [Multi-domain] Cd Length: 138 Bit Score: 47.91 E-value: 7.62e-07

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
2QJT_B      209 VTVDALVIVNDHILMVQRKAHpGKDLWALPGGFLECDETIAQAIIRELFEET 260
Cdd:cd03675   1 VTVAAVVERDGRFLLVEEETD-GRLVLNQPAGHLEPGESLLEAAIRETLEET 51

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: 47.69 E-value: 7.91e-07

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
2QJT_B      210 TVDALVIVNDH--ILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQL 269
Cdd:cd04671   1 YVVAAVIINEQgeVLMIQEAKRSCRGKWYLPAGRVEPGESIVEAAKREVKEETGLKCEPSTL 62

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: 46.78 E-value: 1.39e-06

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
2QJT_B      221 ILMVQRkahPGKDLWALPGGFLECDETIAQAIIRELFEETNIN 263
Cdd:cd03673  18 VLLIHR---PRYDDWSLPKGKLEPGETPEEAAVREVEEETGLR 57

UDP-X diphosphatase; UDP-X diphosphatase hydrolyzes UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-alanine, the last step of the Mur pathway of peptidoglycan biosynthesis. 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: 467601 [Multi-domain] Cd Length: 128 Bit Score: 46.62 E-value: 1.65e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
2QJT_B      215 VIVNDH-ILMVQRKAHpgkDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQL 269
Cdd:cd18891   8 FIQNENkVLLVQDKHT---KEWALPGGFAEVGLSPKENILKEVKEETGLHVEVERL 60

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: 46.44 E-value: 2.23e-06

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
2QJT_B      209 VTVDALVIVNDHILMvQRKAHPGKD--LWALPGGFLECDETIAQAIIRELFEETNINLTHEQLAIA 272
Cdd:cd04683   1 VDVHLLLVRGDEVLL-LRRANTGYDdgWWHLPAGHVEAGETVRAAAVREAKEELGVEIDPEDLRLV 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: 467587 [Multi-domain] Cd Length: 144 Bit Score: 46.41 E-value: 2.96e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
2QJT_B      215 VIVN--DHILmVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQL 269
Cdd:cd18875   8 MIYDgeDRVL-VLDRVKKDWGGYTFPGGHVEPGESFVDSVIREVKEETGLTIKNPEL 63

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: 45.75 E-value: 3.50e-06

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
2QJT_B      209 VTVDALVI-VNDHILMVQRKAHPGK--DLWALPGGFLECDETIAQAIIRELFEETNINLTHEQL 269
Cdd:cd04694   3 VGVVVLIEdSDDRVLLTRRAKHMRTfpGVWVPPGGHVELGESLLEAGLRELQEETGLEVSDIQS 66

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: 45.27 E-value: 4.76e-06

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
2QJT_B      221 ILMVQRkahPGKDLWALPGGFLECDETIAQAIIRELFEETNINLT 265
Cdd:cd18876  14 VLLVKP---TYKDGWELPGGVVEAGESPLQAARREVREELGLDVP 55

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: 5.43e-06

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
2QJT_B      213 ALVIVND--HILMVQR----KAHPGKdlWALPGGFLE-CDETIAQAIIRELFEETNINLTHEQL 269
Cdd:cd03426   8 PLVEGDGelHVLLTKRashlRSHPGQ--IAFPGGKREpGDESPVETALRETEEEIGLPPESVEV 69

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: 45.60 E-value: 7.50e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      209 VTVDALVIVNDH-ILMVQRkaHPGKDLWAL-----PGGFLECDETIAQAIIRELFEETNINLTHEQLAIAKRCEKVFDYP 282
Cdd:cd04693  30 LVVHVWIFNSDGeILIQQR--SPDKKGFPGmweasTGGSVLAGETSLEAAIRELKEELGIDLDADELRPILTIRFDNGFD 107

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
2QJT_B      283 DrsvrgrtishvgLFVFDQWPSLPEIN-AADDAKDVKWISLgSNIKNICDR 332
Cdd:cd04693 108 D------------IYLFRKDVDIEDLTlQKEEVQDVKWVTL-EEILEMIES 145

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: 44.59 E-value: 9.25e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
2QJT_B      218 NDHILMVQRKAHPG---KDLWALPGGFLECDETIAQAIIRELFEETNINLT 265
Cdd:cd04682  10 GDKLLTILRDDKPGipfPNLWDLPGGGREGDETPFACVLRELREELGLALP 60

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: 43.73 E-value: 2.02e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
2QJT_B      198 LWLKApfkpnfVTVdalVIVND--HILMVQRkAHPGKdlWALPGGFLECDETIAQAIIRELFEETNINLTHEQLA 270
Cdd:cd18879  16 LWLPG------VTA---VVLRDagRVLLVRR-ADNGR--WTPVTGIVEPGEQPADAAVREVLEETGVDVEVERLA 78

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: 43.37 E-value: 2.22e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      213 ALVIVNDHILMVQRKahpgKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLaIA 272
Cdd:cd18889   7 AAIFKDDKILLVQEK----DGRWSLPGGWVDVNQSIKENTIKEAKEEAGLDVEPKRI-IA 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: 467574 [Multi-domain] Cd Length: 142 Bit Score: 43.70 E-value: 2.38e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      220 HILMVQRKA--------HPGKDLWalPG-------GFLECDETIAQAIIRELFEETNINLTHEQLAIAKRCEKVFDYPDr 284
Cdd:cd04692  30 HVWLVNPEEgrlllqkrSANKDDF--PGlwdisaaGHIDAGETYEEAAVRELEEELGLTVSPEDLIFLGVIREEVIGGD- 106

                        90       100       110
                ....*....|....*....|....*....|....*...
2QJT_B      285 sVRGRTISHVGLFVFDQWPSLPEINaADDAKDVKWISL 322
Cdd:cd04692 107 -FIDNEFVHVYLYETDRPLEEFKLQ-PEEVAGVVFVDL 142

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: 42.73 E-value: 3.52e-05

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
2QJT_B      213 ALVIVNDHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNI 262
Cdd:cd04669   4 VLVIYDDDKLLLIRRTKPGEEYYVFPGGGIEPGETPEEAALREAVEELGL 53

NUDIX domain;

Pssm-ID: 464330 [Multi-domain] Cd Length: 114 Bit Score: 41.53 E-value: 7.72e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
2QJT_B        213 ALVIVN--DHILMVQRkahPGKDLWA----LPGGFLECDETIAQAIIRelFEETNINLTHEQ 268
Cdd:pfam14815   2 VLVIRNgdGRVLLRKR---PEKGLLGglweFPGGKVEPGETLEEALAR--LEELGIEVEVLE 58

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: 41.96 E-value: 9.00e-05

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
2QJT_B      220 HILMVQRKA--HPGkDLWALPGGFLECDETIAQAIIRELFEETNIN 263
Cdd:cd18877  33 HVLLQHRAWwtHQG-GTWALPGGARDSGETPEAAALRETEEETGLD 77

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: 41.30 E-value: 1.56e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
2QJT_B      209 VTVDALVIVNDHILMVQRKahpGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQL 269
Cdd:cd18883   1 YTARGVIISDEHLLLARVK---GDDKTFLPGGHIEIGESAEIALVRELREELGLSCKVGRY 58

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: 40.66 E-value: 1.56e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
2QJT_B      207 NFVTVDALvIVNDH--ILMVQRKAHpgKDLWALP-----GGFLECDETIAQAIIRELFEETNINLT 265
Cdd:cd24154   1 NFRVVNAF-LINSQgqLWIPRRTAD--KRIFPLAldmsvGGHVSSGETYEQAFVRELQEELNLDLD 63

NADH pyrophosphatase NudC, Nudix superfamily [Nucleotide transport and metabolism];

Pssm-ID: 442065 [Multi-domain] Cd Length: 288 Bit Score: 42.98 E-value: 1.64e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
2QJT_B      211 VDALVIV----NDHILMVQRKAHPGKdLWALPGGFLECDETIAQAIIRELFEETNI 262
Cdd:COG2816 157 TDPAVIVlvtdGDRILLARQARWPPG-RYSLLAGFVEPGETLEQAVRREVFEEVGV 211

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: 40.69 E-value: 2.44e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
2QJT_B      209 VTVDaLVIVNDH--ILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLT 265
Cdd:cd03430  16 VSID-LIIRNEDgeILLGKRNNRPAQGYWFVPGGRILKNETLDDAFKRIAREELGLEVT 73

diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 and similar proteins; Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 (DIPP2), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 4; Nudt4, and other proteins including DIPP1/Nudt3, DIPP3a;APS2/Nudt10 and DIPP3beta;APS1/Nudt11. DIPP regulates the turnover of diphosphoinositol polyphosphates. The turnover of these high-energy diphosphoinositol polyphosphates represents a molecular switching activity with important regulatory consequences. Molecular switching by diphosphoinositol polyphosphates may contribute to regulating intracellular trafficking. Several alternatively spliced transcript variants have been described, but the full-length nature of some variants has not been determined. Isoforms DIPP2alpha and DIPP2beta are distinguishable from each other solely by DIPP2beta possessing one additional amino acid due to intron boundary skidding in alternate splicing. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467551 [Multi-domain] Cd Length: 128 Bit Score: 40.21 E-value: 2.71e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      221 ILMVQ-RKahpgKDLWALPGGFLECDETIAQAIIRELFEEtninltheqlA-----IAKRCEKVFDYPDRSVRGRTISHV 294
Cdd:cd04666  17 VLLITsRK----TGRWILPKGGPEKGETPAEAAAREAWEE----------AgvrgkVLKRPLGVYRYRKRLKGRGLPCRV 82

                        90
                ....*....|....*
2QJT_B      295 GLF------VFDQWP 303
Cdd:cd04666  83 HVFplevteELDDWP 97

ADP-ribose pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase;EC 3.6.1.13, also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 9/Nudt9, 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: 467538 [Multi-domain] Cd Length: 179 Bit Score: 41.16 E-value: 2.97e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      199 WLKAPFKPNFVTVDALVIvndHILMVQRKAHpgkDLWALPGGFLECDETIAQAIIRELFEETNInlTHEQLAIAKRCEKV 278
Cdd:cd03670  30 WKRDADGGNVERSGKKVL---EFVAIKRKDD---GEWAIPGGFVDPGEKVSDTLKREFYEEALN--SLEEPEIEELLEEL 101

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      279 FDYPDRSVRGrtishvglFVFDQ------W---------------PSLPEINAADDAKDVKWISLGSNIK 327
Cdd:cd03670 102 FKDGVEIYKG--------YVDDPrntdnaWmetvavnfhdefgkgVGLLKLEAGDDAGKVKWMDVTSDLN 163

CDP-choline pyrophosphatase; CDP-choline pyrophosphatase catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. 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: 467600 [Multi-domain] Cd Length: 129 Bit Score: 40.10 E-value: 3.44e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
2QJT_B      215 VIVNDH--ILMVQRKAHpGKdlWALPGGFLECDETIAQAIIRELFEETNINLTHEQL 269
Cdd:cd18890   8 VVFNDKeeILLVKEKED-GK--WTLPGGWADVGYTPTEVAAKEVEEETGLEVSPKKL 61

nudix hydrolase

Pssm-ID: 215184 [Multi-domain] Cd Length: 144 Bit Score: 40.23 E-value: 3.45e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
2QJT_B       209 VTVDALVIVNDHILMVQRKAHPGKDLWALPGGFLECDETIAQAIIRELFEETNINLTHEQLA 270
Cdd:PLN02325  10 VAVVVFLLKGNSVLLGRRRSSIGDSTFALPGGHLEFGESFEECAAREVKEETGLEIEKIELL 71

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: 40.28 E-value: 3.66e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
2QJT_B      214 LVIVNDH--ILMVQRKAHPG----KDLWALPGGFLECDETIAQAIIRELFEETNI 262
Cdd:cd04700  18 VVLLNERgdILLVQEKGISGhpekAGLWHIPSGAVEDGENPQDAAVREACEETGL 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: 467548 [Multi-domain] Cd Length: 132 Bit Score: 39.97 E-value: 3.88e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
2QJT_B      218 NDHILMVQRKAHPGKDLwALPGGFLECDETIAQAIIRELFEETNINLTHEQLAIAKRCEKVFDYPDR 284
Cdd:cd04663  12 NRELLVFEHPDFPEAGL-QVPKGTVEPGESPEEAALRELAEETGLTGARVVVDLGSHDEGFEELHQR 77

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

Pssm-ID: 467595 [Multi-domain] Cd Length: 125 Bit Score: 39.32 E-value: 5.99e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
2QJT_B      211 VDALVIVNDHILMVQRKAHPgKDLWALPGGFLECDETIAQAIIRELFEETNI 262
Cdd:cd18884  12 VAAIVEHDGHIVLARNKAWP-EGWYGLVTGFLEAGESPEEAVLREVKEELGL 62

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: 39.80 E-value: 6.68e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      222 LMVQRKAhPGKDLWalPG-------GFLECDETIAQAIIRELFEETNINLTHEQLAIAKrcekvFDY---PDRSVRGRTI 291
Cdd:COG1443  43 LLLQRRA-LTKDHW--PGlwdntvcGHPRAGETYEEAAVRELEEELGITVDDDLRPLGT-----FRYravDANGLVENEF 114

                        90       100       110
                ....*....|....*....|....*....|.
2QJT_B      292 SHVGLFVFDQWPSLPEinaaDDAKDVKWISL 322
Cdd:COG1443 115 CHVFVARLDGPLTPQP----EEVAEVRWVTL 141

Phosphopantetheine adenylyltransferase; Phosphopantetheine adenylyltransferase (PPAT). PPAT is an essential enzyme in bacteria, responsible for catalyzing the rate-limiting step in coenzyme A (CoA) biosynthesis. The dinucleotide-binding fold of PPAT is homologous to class I aminoacyl-tRNA synthetases. CoA has been shown to inhibit PPAT and competes with ATP, PhP, and dPCoA. PPAT is a homohexamer in E. coli.

Pssm-ID: 173914 [Multi-domain] Cd Length: 153 Bit Score: 39.76 E-value: 7.11e-04

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                ....*....|....*....|....*....|....*....|....*....|....*..
2QJT_B        9 ISVFIGRFQPFHKGHLHNIIIALQNSKKVIINIgscFNTPNiKNP-FSFEQRKQMIE 64
Cdd:cd02163   1 IAVYPGSFDPITNGHLDIIERASKLFDEVIVAV---AVNPS-KKPlFSLEERVELIR 53

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: 39.07 E-value: 9.02e-04

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                ....*....|....*....|....*....|....*....|....
2QJT_B      220 HILMVQrkaHPGKDLWALPGGFLECDETIAQAIIRELFEETNIN 263
Cdd:cd03428  18 EFLLLQ---HSYGGHWDFPKGHVEPGESELETALRETKEETGLT 58

RNA pyrophosphohydrolase; Reviewed

Pssm-ID: 234820 [Multi-domain] Cd Length: 156 Bit Score: 39.37 E-value: 9.75e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*....|...
2QJT_B       203 PFKPNfvtVdALVIVNDH--ILMVQRKAHPgkDLWALPGGFLECDETIAQAIIRELFEETNIN 263
Cdd:PRK00714   6 GYRPN---V-GIILLNRQgqVFWGRRIGQG--HSWQFPQGGIDPGETPEQAMYRELYEEVGLR 62

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: 37.99 E-value: 1.83e-03

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                ....*....|....*....|....*....|....*....|....*...
2QJT_B      215 VIVNDH--ILMVQRkahPGKDLWaLPGGFLECDETIAQAIIRELFEET 260
Cdd:cd04684  21 VIFNDEgkVLLVQT---PNGGYF-LPGGGIEPGETPEEALHREVLEET 64

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: 37.28 E-value: 2.73e-03

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                ....*....|....*....|....*....|....*....|....*....|....*....
2QJT_B      213 ALVIVN-DHILMVQRkahPGKDLWA----LPGGFLECDETIAQAIIRELFEETNINLTH 266
Cdd:cd03431   8 VLVLRDgGRVLLEKR---PEKGLLAglweFPLVETEEEEEEAEALLGLLAEELLLILEP 63

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: 36.83 E-value: 4.39e-03

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      226 RKAHPGKdlWALPGGFLECDETIAQAIIRELFEETNINLTHEQLA--IAKRCEKVFDYPDRsvRGRTISHVGLfVFDQWP 303
Cdd:cd04696  24 RGVFPGQ--WALSGGGVEPGERIEEALRREIREELGEQLILSDITpwTFRDDIRIKTYPDG--RQEEIYMIYL-IFDCVS 98

                        90
                ....*....|....*..
2QJT_B      304 SLPEINAADDAKDVKWI 320
Cdd:cd04696  99 ANRDVCINDEFQDYAWV 115

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: 37.50 E-value: 4.84e-03

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2QJT_B      208 FVTVDALVI-----VNDHILMVQ--------RKAHPgkDLWALPGGFLECDETIAQAIIRELFEETNINLtheqlaiaKR 274
Cdd:cd24155  40 FERGDAVAVlpydpVRDEVVLIEqfrigalaRDESP--WLLEIVAGMIDAGETPEDVARREAEEEAGLTL--------DA 109


                ....*..
2QJT_B      275 CEKVFDY 281
Cdd:cd24155 110 LEPIASY 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: 36.38 E-value: 6.66e-03

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                ....*....|....*....|....*....|....*....|....*....|....
2QJT_B      212 DALVIV----NDHILMVQRKAHP-GKDLWALPGGFLECDETIAQAIIRELFEET 260
Cdd:cd24161   4 DAVGVLpitdDGEVVLVEQYRYPlGGWSWEIPAGGWPEGEDPEEAARRELREET 57

nucleoside triphosphatase NudI; Provisional

Pssm-ID: 185369 [Multi-domain] Cd Length: 141 Bit Score: 36.26 E-value: 8.15e-03

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                 ....*....|....*....|....*....|....*....|...
2QJT_B       226 RKAHPGKdlWALPGGFLECDETIAQAIIRELFEE--TNINLTH 266
Cdd:PRK15472  26 RGVFPGQ--WALSGGGVEPGERIEEALRREIREElgEQLLLTE 66