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 1084782384  13 AAVLVLCHKKNGENYLLLTKRSENVAHHKGQICFPGGVKDKNDPTLWDTALRETWEEIGLPKEHVSFRRELSVITTPTGF 92
Cdd:cd03426     3 AAVLIPLVEGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSGF 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1084782384  93 RVTPFVGSITNLHDLNPSPIEIAEVFWVPMNHLLDAKNFSLEKKIYFG--ITYDDPTYIYKDYKIWGATGRIMRDF 166
Cdd:cd03426    83 VVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGprGTYRVPFYPYEGYVIWGLTARILSEL 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 1084782384  13 AAVLVLCHKKNGENYLLLTKRSENVAHHKGQICFPGGVKDKNDPTLWDTALRETWEEIGLPKEHVSFRRELSVITTPTGF 92
Cdd:cd03426     3 AAVLIPLVEGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSGF 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1084782384  93 RVTPFVGSITNLHDLNPSPIEIAEVFWVPMNHLLDAKNFSLEKKIYFG--ITYDDPTYIYKDYKIWGATGRIMRDF 166
Cdd:cd03426    83 VVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGprGTYRVPFYPYEGYVIWGLTARILSEL 158

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1084782384  12 DAAVLVLChkkNGENYLLLTKRSENvAHHKGQICFPGGVKDKNDpTLWDTALRETWEEIGLPKEHVsfrRELSVITTP-- 89
Cdd:COG0494    14 PAVVVVLL---DDDGRVLLVRRYRY-GVGPGLWEFPGGKIEPGE-SPEEAALRELREETGLTAEDL---ELLGELPSPgy 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1084782384  90 TGFRVTPFVGSI---TNLHDLNPSPiEIAEVFWVPMNHLLD 127
Cdd:COG0494    86 TDEKVHVFLARGlgpGEEVGLDDED-EFIEVRWVPLDEALA 125

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1084782384  13 AAVLVLCHKKNGENYLLLTKRSENVAHHKGQICFPGGVKDKNDPTLWDTALRETWEEIGLPKEHVSFRRELSVITTPTGF 92
Cdd:cd03426     3 AAVLIPLVEGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSGF 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1084782384  93 RVTPFVGSITNLHDLNPSPIEIAEVFWVPMNHLLDAKNFSLEKKIYFG--ITYDDPTYIYKDYKIWGATGRIMRDF 166
Cdd:cd03426    83 VVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGprGTYRVPFYPYEGYVIWGLTARILSEL 158

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1084782384  12 DAAVLVLChkkNGENYLLLTKRSENvAHHKGQICFPGGVKDKNDpTLWDTALRETWEEIGLPKEHVsfrRELSVITTP-- 89
Cdd:COG0494    14 PAVVVVLL---DDDGRVLLVRRYRY-GVGPGLWEFPGGKIEPGE-SPEEAALRELREETGLTAEDL---ELLGELPSPgy 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1084782384  90 TGFRVTPFVGSI---TNLHDLNPSPiEIAEVFWVPMNHLLD 127
Cdd:COG0494    86 TDEKVHVFLARGlgpGEEVGLDDED-EFIEVRWVPLDEALA 125

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1084782384  13 AAVLVLChkkNGENYLLLTKRSEnvAHHKGQICFPGGVKDKNDpTLWDTALRETWEEIGLPKEHVSFRRELSVITTPTGF 92
Cdd:pfam00293   5 AVGVVLL---NEKGRVLLVRRSK--KPFPGWWSLPGGKVEPGE-TPEEAARRELEEETGLEPELLELLGSLHYLAPFDGR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1084782384  93 RVTP------FVGSITNLHDLNPSPiEIAEVFWVPMNHLLDAKNFSLEKKIY 138
Cdd:pfam00293  79 FPDEheilyvFLAEVEGELEPDPDG-EVEEVRWVPLEELLLLKLAPGDRKLL 129

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1084782384  14 AVLVLCHKKNGEnyLLLTKRSEnvAHHKGQICFPGGVKDKNDpTLWDTALRETWEEIGLpkeHVSFRRELSVITTPTGFR 93
Cdd:COG1051     8 AVDAVIFRKDGR--VLLVRRAD--EPGKGLWALPGGKVEPGE-TPEEAALRELREETGL---EVEVLELLGVFDHPDRGH 79

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1084782384  94 V--TPFVGSITNlHDLNPSPiEIAEVFWVPMNHLLD 127
Cdd:COG1051    80 VvsVAFLAEVLS-GEPRADD-EIDEARWFPLDELPE 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1084782384  13 AAVLVLCHKKN-GENYLLLTKRSENVaHHKGQICFPGGVKDkNDPTLWDTALRETWEEIGLPKEHVSFRRElsVITTPTG 91
Cdd:cd18877    18 AAGLLLFAPAEdGGPHVLLQHRAWWT-HQGGTWALPGGARD-SGETPEAAALRETEEETGLDADTLRVVGT--HVDDHGG 93

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1084782384  92 FRVTPFVGSITNLHDLNPSPIEIAEVFWVPMNHLLD 127
Cdd:cd18877    94 WSYTTVLASAPEPLPVRPANEESVELRWVPLDEVES 129

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 1084782384   9 NPIDA-AVLVLChkkngENYLLLTKRSENVAhhKGQICFPGGVKDKNDpTLWDTALRETWEEIGLPKEHVSFRRELSVIT 87
Cdd:cd04681     4 NVAAAvGVIIRN-----EGEILFVRRAKEPG--KGKLDLPGGFVDPGE-SAEEALRRELREELGLKIPKLRYLCSLPNTY 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1084782384  88 TPTGFRVTP----FVGSITNLHDLNPSPIEIAEVFWVPMNHL 125
Cdd:cd04681    76 LYKGITYKTcdlfFTAELDEKPKLKKAEDEVAELEWLDLEEI 117

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1084782384  12 DAAVLVLCHKKNGENYLLLTKRSenvAHHK---GQICFPGGVKDKND--PTLWD------------------------TA 62
Cdd:cd18870     1 PAATVILLRDGADGLEVLLLRRS---STMSfmpGAYVFPGGRVDPADrdAPWAGllppdvasasrpgksdpearalriAA 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1084782384  63 LRETWEEIGLpkehvsfrreLSVIT---TPTGFRV---TPF-VGSITNLHDLNPSPIEIAEVFWVPMNHLLDA 128
Cdd:cd18870    78 IRETFEETGL----------LLAWArwiTPPGMPRrfdTRFfLAPLPAGQEPVHDGGETVEARWVTPREALEA 140

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 1084782384  23 NGENYLLLTK-RSENVAHHKgqicFPGGVKDKNDpTLWDTALRETWEEIGL---PKEHVSFRRelsviTTPTGF------ 92
Cdd:cd04670    11 NENNEVLVVQeKYGGPGGWK----LPGGLVDPGE-DIGEAAVREVFEETGIdteFVSILGFRH-----QHPGRFgksdly 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1084782384  93 ---RVTPfvgsiTNLHDLNPSPIEIAEVFWVPMNHLLDAKNFSLEKK 136
Cdd:cd04670    81 fvcRLRP-----LSDEEIKICPEEIAEAKWMPLEEYLKQPNVSQINK 122

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1084782384  17 VLCHKKNGENYLLLTKRsenVAHHKGQICFPGGvKDKNDPTLWDTALRETWEEIGLPKEHVSFRrelSVIT--TPTG--- 91
Cdd:cd18875     5 NMCMIYDGEDRVLVLDR---VKKDWGGYTFPGG-HVEPGESFVDSVIREVKEETGLTIKNPELC---GIKQwiNPDGery 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1084782384  92 ----FRVTPFVGSITnlhdlnpSPIEiAEVFWVPMNHLLDAKNFSLEKKIYFGITYDDPTYIYKDYKIWGATGRI 162
Cdd:cd18875    78 ivflYKTDHFSGELL-------SSEE-GELFWIPIEELKKLPLATDFDEMLRVFESDDLSEFFYYREGDDWNKKL 144

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 1084782384  11 IDAAVLVlcHKKNGEnylLLTKRSENVAHhkgqicF--PGGvkdKNDP--TLWDTALRETWEEIGLPKEHVSFRReLSVI 86
Cdd:cd04690     1 IVKAAVI--IIKDGR---LLLVRKRGTDA------FylPGG---KREPgeTPLQALVRELKEELGLDLDPDSLRF-LGTF 65

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1084782384  87 TTP----TGFRVTPFVGSITNLHDLNPSPiEIAEVFWVPMNHLLDAK 129
Cdd:cd04690    66 EAPaanePGTTVRMTCFTADYDGEPQPAA-EIEELRWLDPADPDDDR 111

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1084782384  27 YLLLTKRSENvahhkgQICFPGgvkdkndptLWDT---------------ALRETWEEIGLpkeHVSFRRELSVITTPTG 91
Cdd:cd04692    40 RLLLQKRSAN------KDDFPG---------LWDIsaaghidagetyeeaAVRELEEELGL---TVSPEDLIFLGVIREE 101

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1084782384  92 FRVTPFVG----------SITNLHDLNPSPIEIAEVFWVPM 122
Cdd:cd04692   102 VIGGDFIDnefvhvylyeTDRPLEEFKLQPEEVAGVVFVDL 142

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 1084782384  12 DAAVLVLCHkkNGENYLLLTKRsenvAHHKGQ--ICFPGGVkdknDP--TLWDTALRETWEEIGLPKEHVS--------F 79
Cdd:cd03429     1 DPAVIVLVT--NGEDKILLARQ----PRWPPGrySLLAGFV----EPgeTLEEAVRREVKEEVGLRVKNVRyvgsqpwpF 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1084782384  80 RRELSVittptGFRVTPFVGSITNLHDlnpspiEIAEVFWVPMNHLLDA 128
Cdd:cd03429    71 PSSLML-----GFTAEADSGEITVDDD------ELEDARWFSRDELPEA 108

translation initiation factor IF-2B alpha subunit; Eukaryotic translation initiation factor 2B subunit alpha (EIF2B1) is one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. 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 1084782384  28 LLLTKRSENVAHHKGQICFPGGVKDKNDPTLwDTALRETWEEIGLPKEHVSFRRE---LSVITTPTG--FRVTPF 97
Cdd:cd18872    13 VLLFRRSDKVGTYQGRWAGISGSIESDDPPL-AAAWREIREETGLTPEDVELLRQgkpFEFTDESLGreWTVHPF 86

isopentenyl-diphosphate Delta-isomerase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1084782384  19 CHKKNGENYLLLTKRsenvAHHKgqICFPGgvkdkndptLW---------------DTALRETWEEIGLpkEHVSFRREL 83
Cdd:PRK03759   39 CYLFDADGRLLVTRR----ALSK--KTWPG---------VWtnsccghpqpgesleDAVIRRCREELGV--EITDLELVL 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1084782384  84 SVI----TTPTG---FRVTP-FVGSITNlhDLNPSPIEIAEVFWVPMNHLLDA 128
Cdd:PRK03759  102 PDFryraTDPNGiveNEVCPvFAARVTS--ALQPNPDEVMDYQWVDPADLLRA 152

dihydroneopterin triphosphate pyrophosphatase; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1084782384   1 MMDPKfisNPIdaAVLVLCHKKNGEnyLLLTKRsenvAHHkgqicfPG------GVKDKnDPTLWDTALRETWEEIGL 72
Cdd:PRK09438    1 MMPYK---RPV--SVLVVIYTPDLG--VLMLQR----ADD------PDfwqsvtGSLEE-GETPAQTAIREVKEETGI 60

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 1084782384  13 AAVLVLCHKkNGEnyLLLTKRseNVAHHKGQICFPGGvkdKNDP--TLWDTALRETWEEIGL 72
Cdd:cd04673     2 VAVGAVVFR-DGR--VLLVRR--GNPPDAGLWSFPGG---KVELgeTLEDAALRELREETGL 55