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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321936  24 HAAVLIAIT-DEAQPKVLLTRRSAYLNSHAGEVSFPGGKRDPQDTSNIVVALREAQEETALNPFDVELIGDLPMQKSRNG 102
Cdd:cd03426    2 RAAVLIPLVeGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSG 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 491321936 103 MLVKPIVGLIPPEVQLSAQPTEIDRIFFASLKNLMEAPPVPYE---VRYAHQSLYFPSMRVENEIVWGLTARMLVAL 176
Cdd:cd03426   82 FVVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYEtflRSGPRGTYRVPFYPYEGYVIWGLTARILSEL 158

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321936  24 HAAVLIAIT-DEAQPKVLLTRRSAYLNSHAGEVSFPGGKRDPQDTSNIVVALREAQEETALNPFDVELIGDLPMQKSRNG 102
Cdd:cd03426    2 RAAVLIPLVeGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSG 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 491321936 103 MLVKPIVGLIPPEVQLSAQPTEIDRIFFASLKNLMEAPPVPYE---VRYAHQSLYFPSMRVENEIVWGLTARMLVAL 176
Cdd:cd03426   82 FVVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYEtflRSGPRGTYRVPFYPYEGYVIWGLTARILSEL 158

8-oxo-dGTP pyrophosphatase MutT and related house-cleaning NTP pyrophosphohydrolases, NUDIX family [Defense mechanisms];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 491321936  17 SRSMREAHAAVLIAITDEAQpkVLLTRRSAYlNSHAGEVSFPGGKRDPQDTSnIVVALREAQEETALNPFDVELIGDLP 95
Cdd:COG0494    7 SEPEHYRPAVVVVLLDDDGR--VLLVRRYRY-GVGPGLWEFPGGKIEPGESP-EEAALRELREETGLTAEDLELLGELP 81

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321936  24 HAAVLIAIT-DEAQPKVLLTRRSAYLNSHAGEVSFPGGKRDPQDTSNIVVALREAQEETALNPFDVELIGDLPMQKSRNG 102
Cdd:cd03426    2 RAAVLIPLVeGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSG 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 491321936 103 MLVKPIVGLIPPEVQLSAQPTEIDRIFFASLKNLMEAPPVPYE---VRYAHQSLYFPSMRVENEIVWGLTARMLVAL 176
Cdd:cd03426   82 FVVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYEtflRSGPRGTYRVPFYPYEGYVIWGLTARILSEL 158

nudix hydrolase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321936  33 DEAQPKVLLTRRSAYLNSHAGEVSFPGGKRDPQDTSNIVVALREAQEETALNPFDVELIGDLPMQKSRNGMLVKPIVGLI 112
Cdd:PLN02709  47 DKNELRVILTKRSSTLSSHPGEVALPGGKRDEEDKDDIATALREAREEIGLDPSLVTIISVLEPFVNKKGMSVAPVIGFL 126

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321936 113 PPEVQLS--AQPTEIDRIFFASLKNLMEAPPVPYE------VRYAHQSL-YFPSMRVENEIVWGLTARMLV----ALFQY 179
Cdd:PLN02709 127 HDKKAFKplPNPAEVEEIFDVPLEMFLKDKNKRAEerehegERYLLQYFdYYSEDKERNFIIWALTAGILIrvasIVYQR 206

                        170
                 ....*....|....*.
gi 491321936 180 GLDYQKEWPFLLNSPT 195
Cdd:PLN02709 207 LPEFQERKPRFWNQPN 222

NUDIX domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 491321936   24 HAAVLIAITDEAQpKVLLTRRSAYlnSHAGEVSFPGGKRDPQDTsNIVVALREAQEETALNPFDVELIGDLPMQKSRNG 102
Cdd:pfam00293   3 RVAVGVVLLNEKG-RVLLVRRSKK--PFPGWWSLPGGKVEPGET-PEEAARRELEEETGLEPELLELLGSLHYLAPFDG 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 491321936  28 LIAITDEAQPKVLLTRRSAYLNsHAGEVSFPGGKRDPQDTSnIVVALREAQEETALNPFDVELIGDLP 95
Cdd:cd18877   23 LFAPAEDGGPHVLLQHRAWWTH-QGGTWALPGGARDSGETP-EAAALRETEEETGLDADTLRVVGTHV 88

8-oxo-dGTP diphosphatase MutT;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 491321936  20 MREAHAAVliAITDEAQPKVLLTRRSAylNSH-AGEVSFPGGKRDPQDTSNIVVAlREAQEETALNPFDVELIGDL 94
Cdd:PRK10776   1 MKKLQIAV--GIIRNPNNEIFITRRAA--DAHmAGKWEFPGGKIEAGETPEQALI-RELQEEVGITVQHATLFEKL 71

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 491321936  25 AAVLIAITDEaqPKVLLTRRSAylNSHAGEVSFPGGKRDP----QDTsnivvALREAQEETAL 83
Cdd:cd04673    2 VAVGAVVFRD--GRVLLVRRGN--PPDAGLWSFPGGKVELgetlEDA-----ALRELREETGL 55

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 491321936  25 AAVLIAITDEaqPKVLLTR--RSAylnshAGEVS--FPGGKRDPQDTSnIVVALREAQEETALNPFDVELIGDL 94
Cdd:cd03424    4 AVAVLAITDD--GKVVLVRqyRHP-----VGRVLleLPAGKIDPGEDP-EEAARRELEEETGYTAGDLELLGSF 69

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 491321936  23 AHAAVLIAIT-DEAQPKVLLTRRSAYlnSHAGEVSFPGG----KRDPQDTsnivvALREAQEETALNPFDVELIG 92
Cdd:cd18873    2 SVTVDCVIFGfDDGELKVLLIKRKNE--PFKGGWALPGGfvreDETLEDA-----ARRELREETGLKDIYLEQLG 69

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321936  27 VLIAITDEAQPkvLLTR---RSAYlnshagevSFPGGKRDPQDTSnIVVALREAQEETALNPFDVELIGD 93
Cdd:cd04665    3 VVVIARYKGKW--LFTRhkeRRGW--------EFPGGKREPGETI-EEAARRELYEETGAVIFELKPLGQ 61

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 491321936  31 ITDEaQPKVLLTRRsayLNSH-AGEVSFPGGKRDPqDTSNIVVALREAQEETALNPFDVELIG 92
Cdd:cd04678    9 VLND-DGKVLLGRR---KGSHgAGTWALPGGHLEF-GESFEECAAREVLEETGLEIRNVRFLT 66

Nudix family hydrolase;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 491321936  19 SMREAHAAVLIaITDeAQPKVLLTRRSAYlNSHAGEVSFPGGKRDPQDTSniVVAL-REAQEE 80
Cdd:PRK08999   1 SMKRIHVAAGV-IRD-ADGRILLARRPEG-KHQGGLWEFPGGKVEPGETV--EQALaRELQEE 58