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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  19 HVVGAGALVINKNtKEVLVVQERSGFfkdKNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLAFRQSHKAiLKK 98
Cdd:cd04670     1 HQVGVGGLVINEN-NEVLVVQEKYGG---PGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFRHQHPG-RFG 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063722001  99 KTDMFFLCVLSPRSY-DITEQKSEILQAKWMPIQEYVDQPWNkkNEMFKFMANICQKK 155
Cdd:cd04670    76 KSDLYFVCRLRPLSDeEIKICPEEIAEAKWMPLEEYLKQPNV--SQINKLVAKLLLEC 131

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  19 HVVGAGALVINKNtKEVLVVQERSGFfkdKNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLAFRQSHKAiLKK 98
Cdd:cd04670     1 HQVGVGGLVINEN-NEVLVVQEKYGG---PGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFRHQHPG-RFG 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063722001  99 KTDMFFLCVLSPRSY-DITEQKSEILQAKWMPIQEYVDQPWNkkNEMFKFMANICQKK 155
Cdd:cd04670    76 KSDLYFVCRLRPLSDeEIKICPEEIAEAKWMPLEEYLKQPNV--SQINKLVAKLLLEC 131

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  21 VGAGALVINKNTKeVLVVQERSGFFKDKnvWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLAFRQSHKAIlkKKT 100
Cdd:COG1051     7 VAVDAVIFRKDGR-VLLVRRADEPGKGL--WALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHPDRG--HVV 81

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1063722001 101 DMFFLCVLSPRSydiTEQKSEILQAKWMPIQE 132
Cdd:COG1051    82 SVAFLAEVLSGE---PRADDEIDEARWFPLDE 110

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  19 HVVGAGALVINKNtKEVLVVQERSGFfkdKNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLAFRQSHKAiLKK 98
Cdd:cd04670     1 HQVGVGGLVINEN-NEVLVVQEKYGG---PGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGFRHQHPG-RFG 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063722001  99 KTDMFFLCVLSPRSY-DITEQKSEILQAKWMPIQEYVDQPWNkkNEMFKFMANICQKK 155
Cdd:cd04670    76 KSDLYFVCRLRPLSDeEIKICPEEIAEAKWMPLEEYLKQPNV--SQINKLVAKLLLEC 131

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  21 VGAGALVINKNTKeVLVVQERSGffKDKNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLAFRQSHKAILKKKT 100
Cdd:cd02883     1 VAVGAVVFDDEGR-VLLVRRSDG--PGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEGRHV 77

                          90       100
                  ....*....|....*....|....*....
gi 1063722001 101 DMFFLCVLSPRSYDITEQKSEILQAKWMP 129
Cdd:cd02883    78 VVLVFLARVVGGEPPPLDDEEISEVRWVP 106

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  20 VVGAGALVINKNtkEVLVVQERSGFFKDKnvWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLAFRQshKAILKKK 99
Cdd:cd04691     1 WLGVGGVVVKEG--KVLLVKRAYGPGKGR--WTLPGGFVEEGETLDEAIVREVLEETGIDAKPVGIIGVRS--GVIRDGK 74

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1063722001 100 TDMFFLCVLSPRSYDITEQKSEILQAKWMPIQE 132
Cdd:cd04691    75 SDNYVVFLLEYVGGEPKPDERENSEAGFLTLEE 107

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  19 HVVGAGALVINKNTKEVLVVqERSgffKD--KNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLaFRQS----H 92
Cdd:cd04681     3 HNVAAAVGVIIRNEGEILFV-RRA---KEpgKGKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYL-CSLPntylY 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1063722001  93 KAILKKKTDMFFLCVLsPRSYDITEQKSEILQAKWMPIQE 132
Cdd:cd04681    78 KGITYKTCDLFFTAEL-DEKPKLKKAEDEVAELEWLDLEE 116

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  20 VVGAGALVINKNTK--EVLVVQERSGffkdkNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLA-----FRQSH 92
Cdd:cd03673     1 VEAAGGVVWRGRGGggEVLLIHRPRY-----DDWSLPKGKLEPGETPEEAAVREVEEETGLRVRLGRPLGttrytYTRKG 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1063722001  93 KAILkKKTDmFFLcvLSPRSYDITEQK-SEILQAKWMPIQE 132
Cdd:cd03673    76 KGIL-KKVH-YWL--MRALGGEFLPQPeEEIDEVRWLPPDE 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  24 GALVINKNTKEVLVVQersGFFKDKNvWKLPTGVINEGEDIWTGVAREVEEETGI-IADFVEVLAFrqSHKAILKKKTDM 102
Cdd:cd03672     5 GAILLNEDLDKVLLVK---GWKSNSS-WGFPKGKINKDESDADCAIREVYEETGFdISDLINDKDY--IELTINGQRVRL 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1063722001 103 FFlCVLSPRSYDI-TEQKSEILQAKWMPIQEYVDQPWNKKNEMFKFMANIC 152
Cdd:cd03672    79 YI-IPGVPEDTPFePQTRKEISKIEWFDIDDLPKNKKKKGKNSNKFYMVNP 128

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  22 GAGALVINKNTKEVLVVQERSGFfkDKNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLAFRQSHKAILKKKTD 101
Cdd:cd03424     4 AVAVLAITDDGKVVLVRQYRHPV--GRVLLELPAGKIDPGEDPEEAARRELEEETGYTAGDLELLGSFYPSPGFSDERIH 81

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1063722001 102 MFFLCVLSPRSYDITEQkSEILQAKWMPIQE 132
Cdd:cd03424    82 LFLAEDLTPVSEQALDE-DEFIEVVLVPLEE 111

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  21 VGAGALVINKNTKeVLVVQERSGFFKDKnvWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLAFRQSHKAILKKKT 100
Cdd:cd04678     3 VGVGVIVLNDDGK-VLLGRRKGSHGAGT--WALPGGHLEFGESFEECAAREVLEETGLEIRNVRFLTVTNDVFEEEGKHY 79

                          90
                  ....*....|
gi 1063722001 101 -DMFFLCVLS 109
Cdd:cd04678    80 vTIFVLAEVD 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  19 HVVgAGALVINKNTKEVLVVQERsgffkdK-NVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLA---------- 87
Cdd:cd03674     1 HFT-ASAFVVNPDRGKVLLVHHR------KlGRWLQPGGHVEPDEDPLEAALREAREETGLDVELLSPLSpdpldidvhp 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063722001  88 -----FRQSHKAIlkkktDMFFLCVLSPRsyDITEQKSEILQAKWMPIQE 132
Cdd:cd03674    74 ipanpGEPAHLHL-----DVRYLAVADGD--EALRKSDESSDVRWFPLDE 116

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063722001  19 HVVGAgalVINKNTKEVLVVQE--RSGFFKdknvWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLA 87
Cdd:cd04671     1 YVVAA---VIINEQGEVLMIQEakRSCRGK----WYLPAGRVEPGESIVEAAKREVKEETGLKCEPSTLLS 64

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  21 VGAGALVINKnTKEVLVVQERSgffkdKNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLA------FRQSHKA 94
Cdd:cd18876     1 AAAGALFTDA-AGRVLLVKPTY-----KDGWELPGGVVEAGESPLQAARREVREELGLDVPVGRLLAvdwvppAGGGDDA 74

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1063722001  95 ILKkktdMFFLCVLSP-RSYDITEQKSEILQAKWMPIQE 132
Cdd:cd18876    75 VLF----VFDGGVLTPeQAAAIRLQDEELSAYRFVTPEE 109

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063722001  23 AGALVINKNTkEVLVVQER--SGFFKDKNVWKLPTGVINEGEDIWTGVAREVEEETGI 78
Cdd:cd04700    16 AGVVLLNERG-DILLVQEKgiSGHPEKAGLWHIPSGAVEDGENPQDAAVREACEETGL 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063722001  34 EVLVvQERSGFFKDKNVWKLPTGVINEGEDIWTGVAREVEEETGIIAD-----FVEVLafrQSHKAILKKKTDMFFLC 106
Cdd:cd04683    12 EVLL-LRRANTGYDDGWWHLPAGHVEAGETVRAAAVREAKEELGVEIDpedlrLVHTM---HRRSDGGRERIDFFFRA 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063722001  21 VGAGALVINKNTkEVLVVQeRSgffkDKNVWKLPTGVINEGEDIWTGVAREVEEETGIIADfVEVLA 87
Cdd:cd18879    19 PGVTAVVLRDAG-RVLLVR-RA----DNGRWTPVTGIVEPGEQPADAAVREVLEETGVDVE-VERLA 78

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 1063722001  22 GAGALVI---NKNTKEVLVvQERSGFFKDKNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLA 87
Cdd:cd18877    18 AAGLLLFapaEDGGPHVLL-QHRAWWTHQGGTWALPGGARDSGETPEAAALRETEEETGLDADTLRVVG 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  17 ASHVvgagaLVINKNtKEVLVvQERSgffKDKNVWklP-------TGVINEGEDIWTGVAREVEEETGIIADFVEVLAFR 89
Cdd:COG1443    31 AFSV-----FVFNSD-GRLLL-QRRA---LTKDHW--PglwdntvCGHPRAGETYEEAAVRELEEELGITVDDDLRPLGT 98

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063722001  90 QSHKAILkkKTDMF-------FLCVLSPrsyDITEQKSEILQAKWMPIQE 132
Cdd:COG1443    99 FRYRAVD--ANGLVenefchvFVARLDG---PLTPQPEEVAEVRWVTLEE 143

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  26 LVINKNTKEVLVVQeRSgffKDKNVWKLPTGVINEGEDIWTGVAREVEEETGIIAD-----------FVEVLAFRQSHKA 94
Cdd:cd04664     7 IYRKDEEGEVLLLK-RT---DDGGFWQSVTGGIEDGETPWQAALRELKEETGLDPLelqlidlnvsnFYEIFDDWRPGVT 82

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1063722001  95 ILKKKTdmFFLCVlsPRSYDITEQkSEILQAKWMPIQE 132
Cdd:cd04664    83 VNTEHV--FAVEV--PEEQPIRLS-PEHTDYRWLPYEE 115

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  26 LVINKNtKEVLVVQERSGffkDKNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLA-----FRQShkaiLkkkt 100
Cdd:cd03429     7 LVTNGE-DKILLARQPRW---PPGRYSLLAGFVEPGETLEEAVRREVKEEVGLRVKNVRYVGsqpwpFPSS----L---- 74

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1063722001 101 dMF-FLCVLSPRsyDITEQKSEILQAKWMPIQEYVD 135
Cdd:cd03429    75 -MLgFTAEADSG--EITVDDDELEDARWFSRDELPE 107

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  21 VGAGALVINKNTKEVLVVQERSGFFkdknvwkLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLA-----FRQSHKAI 95
Cdd:cd04684    16 PGAYAVIFNDEGKVLLVQTPNGGYF-------LPGGGIEPGETPEEALHREVLEETGWEIEIGEFLGnasryFYSPDYDR 88

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1063722001  96 LKKKTDMFFLCVLSPRSYDITEQKSEILqakWMPIQEYVD 135
Cdd:cd04684    89 YYLNIGYFYLAELVRKVSEPTEEDHELV---WLPPEEAAD 125

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1063722001  33 KEVLVVQERSGFfkdknvWKLPTGVINEGEDIWTGVAREVEEETGIIAD 81
Cdd:cd04667    11 DRILLVARRGGR------WLLPGGKIEPGESPLEAAIRELKEETGLAAL 53

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 1063722001  53 LPTGVINEGEDIWTGVAREVEEETGIIADFVEV-LAFRQSHKAILKKKTdMFFLCVLSPR 111
Cdd:cd04663    30 VPKGTVEPGESPEEAALRELAEETGLTGARVVVdLGSHDEGFEELHQRW-FFHLCLAGEP 88

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  19 HVVGAgalVInKNTKEVLVVQeRSgffKDKNV---WKLPTGVINEGEDIWTGVAREVEEETGI---IADFVEVLAFRQSH 92
Cdd:cd03425     2 EVVAA---II-VDDGRVLIAQ-RP---EGKHLaglWEFPGGKVEPGETPEQALVRELREELGIeveVGEPLGTVEHDYPD 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1063722001  93 KAIlkkktDM-FFLCvlspRSYDITEQKSEILQAKWMPIQEYVDQPW 138
Cdd:cd03425    74 FHV-----RLhVYLC----TLWSGEPQLLEHQELRWVTPEELDDLDW 111

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063722001  21 VGAGALVINKNtkEVLVVQERSgfFKDKNVWKLPTGVINEGEDIWTGVAREVEEETGI 78
Cdd:PRK05379  204 VTVDAVVVQSG--HVLLVRRRA--EPGKGLWALPGGFLEQDETLLDACLRELREETGL 257

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  26 LVINKNTKEVLVvQERSGFFKD-KNVWKLP-TGVINEGEDIWTGVAREVEEETGIIA---DFVEVLAFRQSHKAilKKKT 100
Cdd:cd04692    32 WLVNPEEGRLLL-QKRSANKDDfPGLWDISaAGHIDAGETYEEAAVRELEEELGLTVspeDLIFLGVIREEVIG--GDFI 108

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1063722001 101 DM-F---FLCVLSPRSYDITEQKSEILQAKWMPI 130
Cdd:cd04692   109 DNeFvhvYLYETDRPLEEFKLQPEEVAGVVFVDL 142

ADP-ribose pyrophosphatase from Mycobacterium tuberculosis (Mt-ADPRase), and similar proteins; Mycobacterium tuberculosis ADP-ribose pyrophosphatase mt-ADPRase(also called Rv1700) is a NUDIX protein that 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 1063722001  22 GAGALVINKNTKEVLVVQE-----RSgffkdkNVWKLPTGVIN-EGEDIWTGVAREVEEETGIIADFVEVLA 87
Cdd:cd24158    38 GAVAVVALDDDGRVLLIRQyrhpvRR------RLWELPAGLLDvAGEPPLEAAARELAEEADLEAARWEVLV 103

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063722001  21 VGAGALVINKNtkEVLVVQERsgffKD--KNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLA 87
Cdd:cd04679     3 VGCGAAILDDG--RLLLVLRL----RApeAGHWGLPGGKVDWLETVEDAVRREILEELGLEIELTRLLC 65

Nucleoside diphosphate-linked moiety X)) motif 19; Acyl CoA diphosphohydrolase (also known as NUDIX (nucleoside diphosphate linked moiety X))-type motif 10; Nudt19; testosterone-regulated protein rp2) has activity towards CoA, oxidized CoA and a wide range of CoA esters, including choloyl-CoA and branched-chain fatty-acyl-CoA esters. CoA is the major acyl carrier in mammals and a key cofactor in energy metabolism. Dynamic regulation of CoA in different tissues and organs supports metabolic flexibility. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063722001  69 AREVEEETGIiadfveVLAFrqSHkAI----LKKKTD-MFFLCVLsPRSYDITEQKSEILQAKWMPIQEYVDQ 136
Cdd:cd18870    78 IRETFEETGL------LLAW--AR-WItppgMPRRFDtRFFLAPL-PAGQEPVHDGGETVEARWVTPREALEA 140

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  34 EVLVVQERSGFFKdkNVWKLPTGVINEGEDIWTGVAREVEEETGiiadfVEVLAFRQSHKAIL------KKKTDMFFLCV 107
Cdd:cd04686    13 KLLLIRKTRGPYQ--GRYDLPGGSQEFGESLEDALKREFAEETG-----MTVTSYDNLGVYDFfvpwsdKELGDVHHIGV 85

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1063722001 108 LsprsYDI---TEQKSEILQ--------AKWMPIQE 132
Cdd:cd04686    86 F----YDVellDNNISELLQfegqdslgAVWIPLQD 117

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063722001  33 KEVLVVQERSGFF-----KDKNVWKLPTGVINEGEDIWTGVAREVEEETGIIADFVEVLA 87
Cdd:cd04665     1 KHVVVIARYKGKWlftrhKERRGWEFPGGKREPGETIEEAARRELYEETGAVIFELKPLG 60