NCBI Conserved Domain Search

ADP-ribose pyrophosphatase, UDP-glucose pyrophosphatase, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) ( NUDIX (Nucleoside diphosphate-linked moiety X)) motif 5; Nudt5) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

Pssm-ID: 467530 [Multi-domain] Cd Length: 134 Bit Score: 166.91 E-value: 1.07e-53

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  42 HNGAVAVLVVH-VGKILLVRQYRKAIEAHTLEIPAGKLDhDGESPLEAAKRELEEEAQLSANEWKKVVDLVPTPGYCNEK 120
Cdd:cd03424    1 HPGAVAVLAITdDGKVVLVRQYRHPVGRVLLELPAGKID-PGEDPEEAARRELEEETGYTAGDLELLGSFYPSPGFSDER 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 537924563 121 IHLYEAKGIqHLENAAPLDEDEFVSIEWIPVEEVIQKIHNGEITDAKTIIAVQYA 175
Cdd:cd03424   80 IHLFLAEDL-TPVSEQALDEDEFIEVVLVPLEEALEMIEDGEITDAKTLAALLLA 133

Bdellovibrio Bacteriovorus nucleoside diphosphate sugar hydrolase, and similar proteins; Bdellovibrio bacteriovorus nucleoside diphosphate sugar (NDPS) hydrolase Bd3179 has been shown to similarities to the Escherichia coli adenosine diphosphate ribose (ADPR) hydrolase and the guanosine diphosphate mannose (GDPM) hydrolase. It may have a role when Bdellovibrio degrades and metabolizes host cell. ADP-ribose pyrophosphatase (ADPRase) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

Pssm-ID: 467607 [Multi-domain] Cd Length: 173 Bit Score: 162.17 E-value: 2.50e-51

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563   3 DFTEVTVQKEVKYKGGIFTVEHHVVSLPNGKQSTRDIVLHNGAVAVL-VVHVGKILLVRQYRKAIEAHTLEIPAGKLDHd 81
Cdd:cd24159    1 HLEEKTLSSRVVYKGGFLKVHRDQVRLPDGSTSTREYITHPGAVAVVpLLDDGRVVMERQYRYPLKRVFLEFPAGKIDP- 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  82 GESPLEAAKRELEEEAQLSANEWKKVVDLVPTPGYCNEKIHLYEAKGIQHLENAapLDEDEFVSIEWIPVEEVIQKIHNG 161
Cdd:cd24159   80 GEDTLETAKRELLEETGYEAQEWAFLTTIHPAIGYSNEHIEIYLARGLTHVEQK--LDDGEFLEVVEVSLAELLEMVLSG 157

                        170
                 ....*....|.
gi 537924563 162 EITDAKTIIAV 172
Cdd:cd24159  158 EITDVKTIIGL 168

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.

Pssm-ID: 467606 [Multi-domain] Cd Length: 174 Bit Score: 151.99 E-value: 3.28e-47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563   8 TVQKEVKYKGGIFTVEHHVVSLPNGKQSTRDIVLHNGAVAVLVVH-VGKILLVRQYRKAIEAHTLEIPAGKLDHDGESPL 86
Cdd:cd24158    2 VLSSEVVYEGAIWDVRRDTVDLPGGGTVTREYVEHPGAVAVVALDdDGRVLLIRQYRHPVRRRLWELPAGLLDVAGEPPL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  87 EAAKRELEEEAQLSANEWKKVVDLVPTPGYCNEKIHLYEAKGIQHLENA---APLDEDEFVSIEWIPVEEVIQKIHNGEI 163
Cdd:cd24158   82 EAAARELAEEADLEAARWEVLVDLFTSPGFSSEAVRVYLARGLSEVPEAdrhEREDEEADMTLRWVPLDEAVAAVLAGRI 161


                 ....*....
gi 537924563 164 TDAKTIIAV 172
Cdd:cd24158  162 TNSTAVAGV 170

NUDIX family Ndx2; NUDIX family protein Ndx2 found in Thermus thermophilus has ADP-ribose pyrophosphatase (ADPRase) as well as flavin adenine dinucleotide (FAD) activity. ADPRase (EC 3.6.1.13) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the NUDIX hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also contains a 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity.Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467609 [Multi-domain] Cd Length: 137 Bit Score: 134.61 E-value: 7.17e-41

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  47 AVLVVHV---GKILLVRQYRKAIEAHTLEIPAGKLdHDGESPLEAAKRELEEEAQLSANEWKKVVDLVPTPGYCNEKIHL 123
Cdd:cd24161    5 AVGVLPItddGEVVLVEQYRYPLGGWSWEIPAGGW-PEGEDPEEAARRELREETGLRAERWTPLGRFYPSNGVSDERAHV 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 537924563 124 YEAKGIQHLEnAAPLDEDEFVSIEWIPVEEVIQKIHNGEITDAKTIIAVQYAALH 178
Cdd:cd24161   84 FLATGLTPGE-PAPEETEEDLEVRRVPLAEALAMVLDGEITDAMSVAALLLARLH 137

Adp-ribose pyrophosphatase (ADPRase) found in Thermus thermophilus, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) such as found in extreme thermophile Thermus thermophilus (TtADPRase) catalyzes the hydrolysis of ADPR to AMP and ribose 5'-phosphate in the presence of Mg2+ and Zn2+ ions. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

Pssm-ID: 467608 [Multi-domain] Cd Length: 151 Bit Score: 124.92 E-value: 6.04e-37

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  38 DIVLHNGAVAVLVVHVGKILLVRQYRKAIEAHTLEIPAGKLDhDGESPLEAAKRELEEEAQLSANeWKKVVDLVPTPGYC 117
Cdd:cd24160   16 EIVEHADAVAVLALREGRMLFVRQMRPAVGAATLEIPAGLID-PGETPEEAARRELAEETGLSGD-LTYLTRFYVSPGFC 93

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563 118 NEKIHLYEAKGIQhlENAAPLDEDEFVSIEWIPVEEVIQKIHNGEI-TDAKTIIAVQYAA 176
Cdd:cd24160   94 DEKLHVFLAENLR--EVEAHPDEDEAIEVVWMRPEEVLERLRRGEVeFSATTLVGVLYYH 151

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

Pssm-ID: 440260 [Multi-domain] Cd Length: 143 Bit Score: 116.29 E-value: 1.06e-33

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  43 NGAVAVLVVHVGKILLVRQYRKAIEAHTLEIPAGKLDhDGESPLEAAKRELEEEAQLSANEWKKVVDLvPTPGYCNEKIH 122
Cdd:COG0494   14 PAVVVVLLDDDGRVLLVRRYRYGVGPGLWEFPGGKIE-PGESPEEAALRELREETGLTAEDLELLGEL-PSPGYTDEKVH 91

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 537924563 123 LYEAKGIQHLENAAPLDEDEFVSIEWIPVEEVIQKIHNGEItdAKTIIAVQYA 175
Cdd:COG0494   92 VFLARGLGPGEEVGLDDEDEFIEVRWVPLDEALALVTAGEI--AKTLAALARL 142

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

Pssm-ID: 467603 [Multi-domain] Cd Length: 187 Bit Score: 102.22 E-value: 1.05e-27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  11 KEVKYKGgIFTVEHHVVSLP--NGKQS---TRDIVLHNGAVAVLVV--HVGKILLVRQYR-KAIEAH----TLEIPAGKL 78
Cdd:cd24155    7 KETVYDG-FFRLERYRLRHRrfDGGWSaplTREIFERGDAVAVLPYdpVRDEVVLIEQFRiGALARDespwLLEIVAGMI 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  79 DhDGESPLEAAKRELEEEAQLSANEWKKVVDLVPTPGYCNEKIHLY-------EAKGIQHLEnaaplDEDEFVSIEWIPV 151
Cdd:cd24155   86 D-AGETPEDVARREAEEEAGLTLDALEPIASYYPSPGGSTERVHLYlglvdlsDLGGIHGLA-----EEGEDIRVHVVPF 159

                        170       180
                 ....*....|....*....|....*..
gi 537924563 152 EEVIQKIHNGEITDAKTIIAVQYAALH 178
Cdd:cd24155  160 DEAMALLDDGEIDNAPLIIALQWLALN 186

GDP-mannose hydrolase (GDPMK), and similar proteins; GDP-mannose hydrolase (GDPMK) is a NUDIX enzyme that uses GDP-mannose as the preferred substrate. It is distinct from Nudix ADP-ribose hydrolases. GDPMK and ADP-ribose pyrophosphatase seem to use similar catalytic mechanism. However, GDPMK hydrolysis does not rely on a single glutamate as the catalytic base; rather, it is dependent on residues that coordinate the magnesium ions and residues that position the substrate properly for catalysis. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467605 Cd Length: 146 Bit Score: 92.24 E-value: 3.39e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  45 AVAVLVVHV--GKILLVRQYRKAI---EAHT--LEIPAGKLDhdGESPLEAAKRELEEEAQLSANEWKKVVDLVPTPGYC 117
Cdd:cd24157    6 AAAVLLYDPkrKTVVLVRQFRAPAylgGGDGwlIEACAGLLD--GDDPEDCIRREAEEETGYRLGDLEKVFTAYSSPGIV 83

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 537924563 118 NEKIHLYEA---KGIQHLENAAPLDEDEFVSIEWIPVEEVIQKIHNGEITDAKTIIAVQYAAL 177
Cdd:cd24157   84 TERIHLFIAeysSADRVGAGGGLAEEGEDIEVLELPLDEALAMIETGEIRDAKTIILLQYLRL 146

ADP-ribose pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase) (also known as NUDIX (Nucleoside diphosphate-linked moiety X)) motif 5; Nudt5) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity.

Pssm-ID: 467598 [Multi-domain] Cd Length: 149 Bit Score: 75.21 E-value: 1.38e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  45 AVAVLVVHVGK-----ILLVRQYRKAIEAHTLEIPAGKLDhDGESPLEAAKRELEEEAQLSAnewKKVVD----LVPTPG 115
Cdd:cd18888    4 AVAIIAILKRKlkppeLVLVKQYRPPVNAYTIEFPAGLVD-PGESPEQAALRELKEETGYTG---EKVLSvsppLALDPG 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 537924563 116 YCNEKIHLYEAKgI--QHLENAAP---LDEDEFVSIEWIPVEEVIQKIHN 160
Cdd:cd18888   80 LSNANMKLVTVE-VdgDDPENQNPkqeLEDGEFIEVILVPLNELLERLQE 128

NUDIX domain family NudE found in Escherichia coli, and similar proteins; The adenosine nucleotide hydrolase NudE protein in Escherichia coli is a NUDIX hydrolase family member active against ADP ribose, NADH, AP2A and AP3A33, and is classified as a hydrolase (E.C. 3.6.1.-) based on gene annotations. It is an ADPRase (EC 3.6.1.13) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the NUDIX hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also contains a 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467604 [Multi-domain] Cd Length: 134 Bit Score: 71.89 E-value: 1.77e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  44 GAVAVLVVHV---GKILLVRQYRKAIEAHTLEIPAGKLDhDGESPLEAAKRELEEEAQLSANEWKKVVDLVPTPGYCNEK 120
Cdd:cd24156    1 GRGAVMIVPIlddDHLLLIREYAAGTERYELGFPKGLID-PGETPEEAANRELKEEIGFGARQLTLLRELSLAPSYMSHK 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 537924563 121 IHLYEAKGIQH--LENaaplDEDEFVSIEWIPVEEVIQKIHNGEITDAKTIIA 171
Cdd:cd24156   80 MHIVLARDLYPerLEG----DEPEPLEVVRWPLADLDELLADPDFTEARSIAA 128

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 67.70 E-value: 5.84e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  44 GAVAVLVVHVGKILLVRQYRKAiEAHTLEIPAGKLDHdGESPLEAAKRELEEEAQLSANEWkKVVDLVPTPGYCNEKIHL 123
Cdd:COG1051    8 AVDAVIFRKDGRVLLVRRADEP-GKGLWALPGGKVEP-GETPEEAALRELREETGLEVEVL-ELLGVFDHPDRGHVVSVA 84

                         90       100       110
                 ....*....|....*....|....*....|.
gi 537924563 124 YEAkgiqHLENAAPLDEDEFVSIEWIPVEEV 154
Cdd:COG1051   85 FLA----EVLSGEPRADDEIDEARWFPLDEL 111

adenosine nucleotide hydrolase NudE; Provisional

Pssm-ID: 183303 Cd Length: 185 Bit Score: 64.83 E-value: 1.82e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  19 IFTVEHhvVSL--PNGKQSTRDIVLHNGAVAVLVVHV---GKILLVRQYRKAIEAHTLEIPAGKLDHdGESPLEAAKREL 93
Cdd:PRK11762  21 LFRVES--VDLefSNGVERVYERMRPSGRGAVMIVPIlddDTLLLIREYAAGTERYELGFPKGLIDP-GETPLEAANREL 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  94 EEEAQLSANEWKKVVDLVPTPGYCNEKIHLYEAKGI--QHLENaaplDEDEFVSIEWIPVEEVIQKIHNGEITDAKTIIA 171
Cdd:PRK11762  98 KEEVGFGARQLTFLKELSLAPSYFSSKMNIVLAEDLypERLEG----DEPEPLEVVRWPLADLDELLARPDFSEARSVAA 173

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

Pssm-ID: 467528 [Multi-domain] Cd Length: 106 Bit Score: 62.81 E-value: 2.36e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  44 GAVAVLVVHVGKILLVRQYRKAiEAHTLEIPAGKLDHdGESPLEAAKRELEEEA--QLSANEWKKVVDLVPTPGYCNEKI 121
Cdd:cd02883    2 AVGAVVFDDEGRVLLVRRSDGP-GPGGWELPGGGVEP-GETPEEAAVREVREETglDVEVLRLLGVYEFPDPDEGRHVVV 79

                         90       100
                 ....*....|....*....|....*....
gi 537924563 122 HLYEAKGIQhlENAAPLDEDEFVSIEWIP 150
Cdd:cd02883   80 LVFLARVVG--GEPPPLDDEEISEVRWVP 106

nudix-type nucleoside diphosphatase, YffH/AdpP family; Members of this family include proteins of about 200 amino acids, including the recently characterized nudix hydrolase YffH, shows to be highly active as a GDP-mannose pyrophosphatase. It also includes the C-terminal half of a 361-amino acid protein, TrgB from Rhodobacter sphaeroides, shown experimentally to help confer tellurite resistance. This model also hits a region near the C-terminus of a 1092-amino acid protein of C. elegans. [Unknown function, Enzymes of unknown specificity]

Pssm-ID: 129162 [Multi-domain] Cd Length: 185 Bit Score: 62.15 E-value: 2.42e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563   36 TRDIVLHNGAVAVLVVHVGK--ILLVRQYRKAIEAHT-----LEIPAGKLDhDGESPLEAAKRELEEEAQLSANEWKKVV 108
Cdd:TIGR00052  37 TREIYDRGNAAAVLLYDPKKdtVVLIEQFRIAAYVNGeepwlLELSAGMVE-KGESPEDVARREAIEEAGYQVKNLRKLL 115

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 537924563  109 DLVPTPGYCNEKIHLYEAKGIQHLE-NAAPLDEDEFVSIEWIPVEEVIQKIHNGEITDAKTIIAVQY 174
Cdd:TIGR00052 116 SFYMSPGGVTELIHLFIAEVDDNQAaGIGGGADEEEIEVLHLVFSQALQWIKEGKIDNGKTVILLQW 182

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 60.57 E-value: 2.81e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563   40 VLHNGAVAVLVVHVGKILLVRQYRKAIEAHtLEIPAGKLDhDGESPLEAAKRELEEEAQLSANEWKKVVDLVPTPGY--- 116
Cdd:pfam00293   1 KRRVAVGVVLLNEKGRVLLVRRSKKPFPGW-WSLPGGKVE-PGETPEEAARRELEEETGLEPELLELLGSLHYLAPFdgr 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 537924563  117 ---CNEKIHLYEAkgiQHLENAAPLDEDEFVSIEWIPVEEVIQKIHN 160
Cdd:pfam00293  79 fpdEHEILYVFLA---EVEGELEPDPDGEVEEVRWVPLEELLLLKLA 122

GDP-mannose pyrophosphatase NudK; Provisional

Pssm-ID: 184971 Cd Length: 191 Bit Score: 57.16 E-value: 1.99e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  43 NGAVAVLV-VHVGKILLVRQYRKAI------EAHTLEIPAGKLDHDgeSPLEAAKRELEEEAQLSANEWKKVVDLVPTPG 115
Cdd:PRK15009  46 NGATILLYnAKKKTVVLIRQFRVATwvngneSGQLIETCAGLLDND--EPEVCIRKEAIEETGYEVGEVRKLFELYMSPG 123

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563 116 YCNEKIHLYEAK-GIQHLENAAPLDEDEFVSIEWIPVEEVIQKIHNGEITDAKTIIAVQY 174
Cdd:PRK15009 124 GVTELIHFFIAEySDSQRANAGGGVEDEDIEVLELPFSQALEMIKTGEIRDGKTVLLLNY 183

ADP-ribose pyrophosphatase NudF; Provisional

Pssm-ID: 182682 [Multi-domain] Cd Length: 202 Bit Score: 56.67 E-value: 3.34e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  56 ILLVRQYR-KAIEAHT----LEIPAGKLDhDGESPLEAAKRELEEEAQLSANEWKKVVDLVPTPGYCNEKIHLY------ 124
Cdd:PRK10729  64 VVLIEQIRiAAYDTSEtpwlLEMVAGMIE-EGESVEDVARREAIEEAGLIVGRTKPVLSYLASPGGTSERSSIMvgevda 142

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 537924563 125 -EAKGIQHLEnaaplDEDEFVSIEWIPVEEVIQKIHNGEITDAKTIIAVQYAALH 178
Cdd:PRK10729 143 tTASGIHGLA-----DENEDIRVHVVSREQAYQWVEEGKIDNAASVIALQWLQLH 192

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

Pssm-ID: 467564 [Multi-domain] Cd Length: 135 Bit Score: 51.03 E-value: 1.28e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  42 HN--GAVAVLVVHVGKILLVRQyRKAIEAHTLEIPAGKLDHdGESPLEAAKRELEEEAQLSANEWKKVVDLvPtpgycNE 119
Cdd:cd04681    3 HNvaAAVGVIIRNEGEILFVRR-AKEPGKGKLDLPGGFVDP-GESAEEALRRELREELGLKIPKLRYLCSL-P-----NT 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 537924563 120 kihlYEAKGIQ----------HLENAAPL--DEDEFVSIEWIPVEEV 154
Cdd:cd04681   75 ----YLYKGITyktcdlfftaELDEKPKLkkAEDEVAELEWLDLEEI 117

MutT homolog 2; MutT Homolog 2 (MTH2; EC 3.6.1.9), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 15/Nudt15, may catalyze the hydrolysis of nucleoside diphosphates, triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP, and prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP. MTH2 may also play a role in DNA synthesis and cell cycle progression by stabilizing PCNA. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467561 [Multi-domain] Cd Length: 128 Bit Score: 50.64 E-value: 1.40e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 537924563  46 VAVLVVH-VGKILLVRqyRK-AIEAHTLEIPAGKLDHdGESPLEAAKRELEEEAQLSANEWKK---VVDLVPTPGY 116
Cdd:cd04678    5 VGVIVLNdDGKVLLGR--RKgSHGAGTWALPGGHLEF-GESFEECAAREVLEETGLEIRNVRFltvTNDVFEEEGK 77

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

Pssm-ID: 467557 [Multi-domain] Cd Length: 128 Bit Score: 50.21 E-value: 2.14e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 537924563  45 AVAVLVVHVGKILLVRQyRKAIEAHTLEIPAGKLDHdGESPLEAAKRELEEEAQLSA 101
Cdd:cd04673    3 AVGAVVFRDGRVLLVRR-GNPPDAGLWSFPGGKVEL-GETLEDAALRELREETGLEA 57

nudix hydrolase; Provisional

Pssm-ID: 215602 Cd Length: 291 Bit Score: 52.13 E-value: 2.27e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  13 VKYKGGIFTVEhhvvslpnGKQSTRDIVLHNG-AVAVLVVHVGK----ILLVRQYRKAIEAHTLEIPAGKLDHDGESPLE 87
Cdd:PLN03143 105 LKFKADIIDKE--------TGQKVPGIVFARGpAVAVLILLESEgetyAVLTEQVRVPVGKFVLELPAGMLDDDKGDFVG 176

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  88 AAKRELEEEAQLSANEwKKVVDL------------VPTPGYCNEKIHLYEAKGIQHLENAAPL--------DEDEFVSIE 147
Cdd:PLN03143 177 TAVREVEEETGIKLKL-EDMVDLtafldpstgcrmFPSPGGCDEEISLFLYRGHVDKETIRQLqgketglrDHGELIKVH 255

                        170       180
                 ....*....|....*....|....*
gi 537924563 148 WIPVEEVIQKihngeITDAKTIIAV 172
Cdd:PLN03143 256 VVPYRELWRM-----TADAKVLMAI 275

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

Pssm-ID: 467579 [Multi-domain] Cd Length: 118 Bit Score: 48.77 E-value: 5.73e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 537924563  45 AVAVLVVHVGKILLVRqyRKAIEAHTLEIPAGKLDhDGESPLEAAKRELEEEAQLSAnewkKVVDLVPT 113
Cdd:cd04699    4 SVKGVIFDNGRVLLLR--RSRAGAGEWELPGGRLE-PGESPEEALKREVKEETGLDV----SVGELLDT 65

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

Pssm-ID: 467588 [Multi-domain] Cd Length: 121 Bit Score: 48.74 E-value: 6.49e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  44 GAVAVLVVH-VGKILLVR-QYRKaieahTLEIPAGKLDhDGESPLEAAKRELEEE-------AQLsanewkKVVDLVPTP 114
Cdd:cd18876    1 AAAGALFTDaAGRVLLVKpTYKD-----GWELPGGVVE-AGESPLQAARREVREElgldvpvGRL------LAVDWVPPA 68

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 537924563 115 GYCNEKI-HLYEAKGIQHLENAA-PLDEDEFVSIEWIPVEE 153
Cdd:cd18876   69 GGGDDAVlFVFDGGVLTPEQAAAiRLQDEELSAYRFVTPEE 109

NUDIX domain family found in Deinococcus radiodurans, and similar proteins; Deinococcus radiodurans protein DR_0079 is one of 21 NUDIX hydrolases that it encodes, and it has been observed to have a marked preference for cytosine ribonucleoside 5'-diphosphate (CDP) and cytosine ribonucleoside 5'-triphosphate (CTP), and for their corresponding deoxyribose nucleotides, dCDP and dCTP, to a lesser degree. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467602 [Multi-domain] Cd Length: 121 Bit Score: 47.59 E-value: 1.85e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  82 GESPLEAAKRELEEEAQL--SANEWKKVVDLVPTPGYCNEKIHLYEakgIQHleNAAP-LDEDEFVSIEWIPVEEVIQKI 158
Cdd:cd24154   43 GETYEQAFVRELQEELNLdlDQLSYRVLGKLTPYEHGVSAFMKVYE---IRS--DETPdYNPDDFSEAFWLTPEELLKRI 117


                 ....
gi 537924563 159 HNGE 162
Cdd:cd24154  118 AAGE 121

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

Pssm-ID: 467589 [Multi-domain] Cd Length: 141 Bit Score: 47.35 E-value: 2.92e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  42 HNGAVAVLVVHV---GKILLVRQYRkAIEAH---TLEIPAGKLDHdGESPLEAAKRELEEEAQLSAN------------- 102
Cdd:cd18877   15 RHGAAGLLLFAPaedGGPHVLLQHR-AWWTHqggTWALPGGARDS-GETPEAAALRETEEETGLDADtlrvvgthvddhg 92

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 537924563 103 EWK--KVVDLVPTPgycnekihlyeakgiqhlENAAPLDEdEFVSIEWIPVEEV 154
Cdd:cd18877   93 GWSytTVLASAPEP------------------LPVRPANE-ESVELRWVPLDEV 127

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

Pssm-ID: 467533 [Multi-domain] Cd Length: 136 Bit Score: 47.14 E-value: 3.74e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  76 GKLDhDGESPLEAAKRELEEEAQLSANEWKKVVDL---VPTPGYcNEKIHLYEA---KGiqhlenaAPLDEDEfVSIEWI 149
Cdd:cd03427   34 GKVE-PGETIEEAAVRELEEEAGLTATELEKVGRLkfeFPDDPE-AMDVHVFRAdswTG-------EPQETEE-MRPQWF 103


                 ....*
gi 537924563 150 PVEEV 154
Cdd:cd03427  104 DLDDI 108

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

Pssm-ID: 467572 [Multi-domain] Cd Length: 123 Bit Score: 46.76 E-value: 4.19e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 537924563  45 AVAVLVVHVGKILLVRQYRKAIeahtLEIPAGKLDhDGESPLEAAKRELEEE 96
Cdd:cd04690    3 KAAVIIIKDGRLLLVRKRGTDA----FYLPGGKRE-PGETPLQALVRELKEE 49

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

Pssm-ID: 441052 [Multi-domain] Cd Length: 162 Bit Score: 47.12 E-value: 5.96e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  82 GESPLEAAKRELEEEAQLSANEWKKVVD------LVPTPGYCNEKIHLYEAkgiqHLENAAPLDEDEFVSIEWIPVEEVI 155
Cdd:COG1443   70 GETYEEAAVRELEEELGITVDDDLRPLGtfryraVDANGLVENEFCHVFVA----RLDGPLTPQPEEVAEVRWVTLEELL 145


                 ....*..
gi 537924563 156 QKIHNGE 162
Cdd:COG1443  146 ALLEAGP 152

RNA pyrophosphohydrolase; The initiation of mRNA degradation often requires deprotection of its 5' end. In eukaryotes, the 5'-methylguanosine (cap) structure is principally removed by the NUDIX family decapping enzyme Dcp2, yielding a 5'-monophosphorylated RNA that is a substrate for 5' exoribonucleases. In bacteria, the 5'-triphosphate group of primary transcripts is also converted to a 5' monophosphate by a NUDIX protein called RNA pyrophosphohydrolase (RppH), allowing access to both endo- and 5' exoribonucleases. NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

Pssm-ID: 467550 [Multi-domain] Cd Length: 121 Bit Score: 43.78 E-value: 4.17e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 537924563  46 VAVLVVHVGKILLVRQYRKaieaHTLEIPAGKLDHdGESPLEAAKRELEEEA 97
Cdd:cd04665    3 VVVIARYKGKWLFTRHKER----RGWEFPGGKREP-GETIEEAARRELYEET 49

thiamine diphosphokinase Tnr3 from Schizosaccharomyces pombe and similar proteins; Tnr3 is a bifunctional enzyme composed of a C-terminal thiamine pyrophosphokinase domain, which transfers pyrophosphate from ATP to thiamine and an N-terminal NUDIX hydrolase domain that converts oxidized derivatives of thiamine diphosphate (oxothiamine and oxythiamine) to their respective monophosphates. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belong to this superfamily requires a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467544 Cd Length: 153 Bit Score: 42.87 E-value: 1.54e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  76 GKLDH-------DGESPLEAAKRELEEEAQLSANEWKKVV---------DLVPTPGYCNEKIHLYEakgiqhLEnaapLD 139
Cdd:cd03676   37 GKLDNlvaggvpAGESPLETLVREAEEEAGLPEDLARQARpaagrvsyfYRSDEGGLQPEVLYVYD------LE----LP 106

                         90       100       110
                 ....*....|....*....|....*....|...
gi 537924563 140 ED--------EFVSIEWIPVEEVIQKIHNGEIT 164
Cdd:cd03676  107 EDfvpkpqdgEVESFELMSVDEVLEALRAGEFK 139

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

Pssm-ID: 467542 [Multi-domain] Cd Length: 130 Bit Score: 42.25 E-value: 1.80e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  74 PAGKLDHDgESPLEAAKRELEEEAQLSAN---EWKKV---VDLVPTPGYCNEKIH-------LYEAKgiqhlENAAPLDE 140
Cdd:cd03674   30 PGGHVEPD-EDPLEAALREAREETGLDVEllsPLSPDpldIDVHPIPANPGEPAHlhldvryLAVAD-----GDEALRKS 103

                         90
                 ....*....|....
gi 537924563 141 DEFVSIEWIPVEEV 154
Cdd:cd03674  104 DESSDVRWFPLDEL 117

UDP-glucose pyrophosphatase; UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

Pssm-ID: 467597 [Multi-domain] Cd Length: 181 Bit Score: 42.54 E-value: 2.88e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  31 NGKQSTRDIVLHNGAVAVLVVHVGK--ILLVRQYRKAIEAH----------------------TLEIPAGKLDHDgESPL 86
Cdd:cd18887    4 NGKKKTWDFVKSHDSVAILLYNKTRdaFVLVKQFRPAVYASqvraaernggkdtekyppelgyTYELCAGLVDKD-KSLE 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  87 EAAKRELEEEA--QLSANEWKKV---VDLVPTPG------YC----NEKIHlyEAKGIQHlenaapldEDEFVSIEWIPV 151
Cdd:cd18887   83 EIAQEEILEECgyDVPLEDLEKItsfRSGVGTSGsrqtlfYAevtdDMKVS--EGGGVEE--------EGEMIEVVELPV 152

                        170
                 ....*....|..
gi 537924563 152 EEVIQKIHNGEI 163
Cdd:cd18887  153 EEAKEFIFDEEI 164

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

Pssm-ID: 467552 [Multi-domain] Cd Length: 117 Bit Score: 41.50 E-value: 3.33e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 537924563  48 VLVVHVGKILLVRQyRKAIEAhtleIPAGKLDHdGESPLEAAKRELEEEAQLSANE 103
Cdd:cd04667    5 VICRRGDRILLVAR-RGGRWL----LPGGKIEP-GESPLEAAIRELKEETGLAALS 54

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

Pssm-ID: 467549 [Multi-domain] Cd Length: 132 Bit Score: 40.70 E-value: 6.33e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  75 AGKLDhDGESPLEAAKRELEEEAQLSANEWKKV---------VDLVPTPGYCNEKIHLYeakgiqhlenAAPLDEDEFVS 145
Cdd:cd04664   32 TGGIE-DGETPWQAALRELKEETGLDPLELQLIdlnvsnfyeIFDDWRPGVTVNTEHVF----------AVEVPEEQPIR 100

                         90       100
                 ....*....|....*....|.
gi 537924563 146 I-------EWIPVEEVIQKIH 159
Cdd:cd04664  101 LspehtdyRWLPYEEAAELLF 121

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

Pssm-ID: 467543 [Multi-domain] Cd Length: 138 Bit Score: 40.97 E-value: 6.86e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  46 VAVLVVHVGKILLVRQYRKaiEAHTLEIPAGKLDHdGESPLEAAKRELEEEAQLSA--NEWKKVVDLVPTPGYCNEKIHL 123
Cdd:cd03675    3 VAAVVERDGRFLLVEEETD--GRLVLNQPAGHLEP-GESLLEAAIRETLEETGWEVepTALLGIYQWTAPDNGVTYLRFA 79

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 537924563 124 YEAKGIQHLENaAPLDEDeFVSIEWIPVEEVIQKIH 159
Cdd:cd03675   80 FAGELLEHLPD-QPLDSG-IIRAHWLTLEEILALQA 113

NADH pyrophosphatase; NADH pyrophosphatase, also known as NUDIX (nucleoside diphosphate linked moiety X)) motif 13/Nudt13, is thought to have NADH pyrophosphatase activity, be involved in NADH metabolic process and NADP catabolic process, catalyzing the cleavage of NADH into reduced nicotinamide mononucleotide (NMNH) and AMP, and located in mitochondrion. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity. Members of this family are also recognized by the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. A block of 8 conserved amino acids downstream of the NUDIX motif is thought to give NADH pyrophosphatase its specificity for NADH. NADH pyrophosphatase forms a dimer.

Pssm-ID: 467535 [Multi-domain] Cd Length: 126 Bit Score: 40.17 E-value: 9.45e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 537924563  45 AVAVLVVH-VGKILLVRQYRKAIEAHTLeiPAGKLDHdGESPLEAAKRELEEEA 97
Cdd:cd03429    3 AVIVLVTNgEDKILLARQPRWPPGRYSL--LAGFVEP-GETLEEAVRREVKEEV 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.

Pssm-ID: 467595 [Multi-domain] Cd Length: 125 Bit Score: 40.09 E-value: 1.06e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  46 VAVLVVHVGKILLVRQyrKAIEAHTLEIPAGKLDHdGESPLEAAKRELEEEAQLSANEwKKVVDLVPTPGYcNEKIHLYE 125
Cdd:cd18884   12 VAAIVEHDGHIVLARN--KAWPEGWYGLVTGFLEA-GESPEEAVLREVKEELGLDGHE-AKFIGHYAFPER-NQLIIAYH 86

                         90       100
                 ....*....|....*....|..
gi 537924563 126 AKGIQHLENAAPLDEDEFVSIE 147
Cdd:cd18884   87 VRARGNVKLNEELDDYKIVPID 108

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

Pssm-ID: 467569 [Multi-domain] Cd Length: 130 Bit Score: 39.97 E-value: 1.13e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  54 GKILLVRQYRkAIEAHTLEIPAGKLDHdGESPLEAAKRELEEEAQLSANEWKKV---VDLVPTPGYCNEKIH----LYEA 126
Cdd:cd04686   12 DKLLLIRKTR-GPYQGRYDLPGGSQEF-GESLEDALKREFAEETGMTVTSYDNLgvyDFFVPWSDKELGDVHhigvFYDV 89

                         90       100       110
                 ....*....|....*....|....*....|...
gi 537924563 127 kgiqHLENAAPLDEDEFVS-----IEWIPVEEV 154
Cdd:cd04686   90 ----ELLDNNISELLQFEGqdslgAVWIPLQDL 118

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

Pssm-ID: 467548 [Multi-domain] Cd Length: 132 Bit Score: 39.97 E-value: 1.21e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 537924563  45 AVAVLVVHVGKILLVRQYRKAIEAhTLEIPAGKLDHdGESPLEAAKRELEEEAQLSA 101
Cdd:cd04663    3 VCAYVTRGRNRELLVFEHPDFPEA-GLQVPKGTVEP-GESPEEAALRELAEETGLTG 57

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

Pssm-ID: 467574 [Multi-domain] Cd Length: 142 Bit Score: 40.23 E-value: 1.30e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  50 VVHV-------GKILLvrQYR---KAIEAHTLEIP-AGKLDHdGESPLEAAKRELEEEAQLSAnEWKKVVDLVPTP---- 114
Cdd:cd04692   28 TVHVwlvnpeeGRLLL--QKRsanKDDFPGLWDISaAGHIDA-GETYEEAAVRELEEELGLTV-SPEDLIFLGVIReevi 103

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 537924563 115 ---GYCNEKIHLYEAKGIQHLEnAAPLDEDEFVSIEWIPV 151
Cdd:cd04692  104 ggdFIDNEFVHVYLYETDRPLE-EFKLQPEEVAGVVFVDL 142

diadenosine hexaphosphate (Ap6A) hydrolase; Diadenosine hexaphosphate (Ap6A) hydrolase is a member of the NUDIX hydrolase superfamily. Ap6A hydrolase specifically hydrolyzes diadenosine polyphosphates, but not ATP or diadenosine triphosphate, and it generates ATP as the product. Ap6A, the most preferred substrate, hydrolyzes to produce two ATP molecules, which is a novel hydrolysis mode for Ap6A. These results indicate that Ap6A hydrolase is a diadenosine polyphosphate hydrolase. It requires the presence of a divalent cation, such as Mn2+, Mg2+, Zn2+, and Co2+, for activity. Members of the NUDIX hydrolase superfamily are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site.

Pssm-ID: 467541 [Multi-domain] Cd Length: 131 Bit Score: 39.84 E-value: 1.46e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  74 PAGKLDhDGESPLEAAKRELEEEAQLSAnewkKVVDLVPT--------PGYCNEKIHLYEAKGIQhlENAAPLDEDEFVS 145
Cdd:cd03673   32 PKGKLE-PGETPEEAAVREVEEETGLRV----RLGRPLGTtrytytrkGKGILKKVHYWLMRALG--GEFLPQPEEEIDE 104


                 ....*...
gi 537924563 146 IEWIPVEE 153
Cdd:cd03673  105 VRWLPPDE 112

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

Pssm-ID: 467555 [Multi-domain] Cd Length: 130 Bit Score: 39.22 E-value: 2.07e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 537924563  45 AVAVLVVHVGKILLVRQYRKAIeAHTLEIPAGKLDHdGESPLEAAKRELEEEAQLSA 101
Cdd:cd04671    3 VAAVIINEQGEVLMIQEAKRSC-RGKWYLPAGRVEP-GESIVEAAKREVKEETGLKC 57

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

Pssm-ID: 467560 [Multi-domain] Cd Length: 137 Bit Score: 39.42 E-value: 2.36e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 537924563  36 TRDIVLhNGAVAVLVVHVGKILLvrQYRKaiEAHTLEIPAGKLDHdGESPLEAAKRELEEEAQLSANE 103
Cdd:cd04677    7 HRPLIL-VGAAVIILNEQGRILL--QKRT--DTGDWGLPGGAMEL-GESLEETARREVFEETGLTVEE 68

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

Pssm-ID: 467573 [Multi-domain] Cd Length: 122 Bit Score: 38.82 E-value: 3.13e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 537924563  45 AVAVLVVHVGKILLVRQYRKAIEAHTLeIPAGKLdHDGESPLEAAKRELEEEAQLSA 101
Cdd:cd04691    3 GVGGVVVKEGKVLLVKRAYGPGKGRWT-LPGGFV-EEGETLDEAIVREVLEETGIDA 57

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

Pssm-ID: 467593 [Multi-domain] Cd Length: 130 Bit Score: 38.78 E-value: 3.93e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 537924563  42 HNGAVAVLVVHVGKILLvrQYRKAIEAhtleIPA--------GKLDhDGESPLEAAKRELEEE 96
Cdd:cd18882    1 HEVAIAILYDDRGKVLL--QLRDDKPG----IPYpgywglfgGHLE-PGETPEEAIRRELEEE 56

plant diadenosine tetraphosphate (Ap4A) hydrolase and similar proteins; Diadenosine tetraphosphate (Ap4A) hydrolase is a member of the NUDIX hydrolase superfamily. Members of this family are well represented in a variety of prokaryotic and eukaryotic organisms. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one group (represented by this subfamily) and fungi/animals/archaea enzymes fall into another. Bacterial enzymes are found in both subfamilies. Ap4A is a potential by-product of aminoacyl tRNA synthesis, and accumulation of Ap4A has been implicated in a range of biological events, such as DNA replication, cellular differentiation, heat shock, metabolic stress, and apoptosis. Ap4A hydrolase cleaves Ap4A asymmetrically into ATP and AMP. It is important in the invasive properties of bacteria and thus presents a potential target for the inhibition of such invasive bacteria. Besides the signature NUDIX motif (G[X5]E[X7]REUXEEXGU where U is Ile, Leu, or Val), Ap4A hydrolase is structurally similar to the other members of the NUDIX hydrolase superfamily with some degree of variations. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies.

Pssm-ID: 467539 [Multi-domain] Cd Length: 147 Bit Score: 38.70 E-value: 4.34e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  74 PAGKLDhDGESPLEAAKRELEEEAQLSAN---------EW------KKVVDLVPTPGYCNEKIHLY------EAKGIqhl 132
Cdd:cd03671   32 PQGGID-EGEDPEEAALRELYEETGLSPEdveiiaetpDWltydlpEDLIRKGWGGKYRGQKQKWFlfrftgDDSEI--- 107

                         90       100
                 ....*....|....*....|....*.
gi 537924563 133 eNAAPLDEDEFVSIEWIPVEEVIQKI 158
Cdd:cd03671  108 -NLDTHEHPEFDAWRWVDLEELPDLV 132

Predicted NTP pyrophosphohydrolase, NUDIX family [Nucleotide transport and metabolism, General function prediction only];

Pssm-ID: 443295 [Multi-domain] Cd Length: 153 Bit Score: 38.65 E-value: 4.40e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 537924563  42 HNGAVAVLVVHVGKILLVRQyrkaiEAHTLEIPAGKLDhDGESPLEAAKRELEEE 96
Cdd:COG4119   14 RDGGLEVLLVHPGGPFWARK-----DEGAWSIPKGEYE-PGEDPLAAARREFAEE 62

MutT pyrophosphohydrolase; The MutT pyrophosphohydrolase is a prototypical NUDIX hydrolase that catalyzes the hydrolysis of nucleoside and deoxynucleoside triphosphates (NTPs and dNTPs) by substitution at a beta-phosphorus to yield a nucleotide monophosphate (NMP) and inorganic pyrophosphate (PPi). This enzyme requires two divalent cations for activity; one coordinates the phosphoryl groups of the NTP/dNTP substrate, and the other coordinates to the enzyme. It also contains the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as metal binding and catalytic site. MutT pyrophosphohydrolase is important in preventing errors in DNA replication by hydrolyzing mutagenic nucleotides such as 8-oxo-dGTP (a product of oxidative damage), which can mispair with template adenine during DNA replication, to guanine nucleotides.

Pssm-ID: 467531 [Multi-domain] Cd Length: 123 Bit Score: 38.20 E-value: 4.66e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 537924563  46 VAVLVVHVGKILLVRqyRKAIEAHTL--EIPAGKLDhDGESPLEAAKRELEEE 96
Cdd:cd03425    4 VAAIIVDDGRVLIAQ--RPEGKHLAGlwEFPGGKVE-PGETPEQALVRELREE 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.

Pssm-ID: 467566 [Multi-domain] Cd Length: 137 Bit Score: 38.35 E-value: 4.79e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 537924563  45 AVAVLVVHVGKILLVRQYRKAIEAHTLEIPAGKLDhDGESPLEAAKRELEEEA 97
Cdd:cd04683    2 DVHLLLVRGDEVLLLRRANTGYDDGWWHLPAGHVE-AGETVRAAAVREAKEEL 53

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

Pssm-ID: 467596 [Multi-domain] Cd Length: 147 Bit Score: 38.37 E-value: 5.29e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  76 GKLDhDGESPLEAAKRELEEEAQLSANEW--KKVVDLVPTPGYCNEKIHLYEAkgiqHLENAAPLDED-----EFVSIEW 148
Cdd:cd18886   32 GKLE-PGESPEECAIREVFEETGLELEDLqlRGIVTFPSFDGGEDWLMYVFLA----EAFSGELVESDregilAWVPIDW 106


                 ..
gi 537924563 149 IP 150
Cdd:cd18886  107 LL 108

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

Pssm-ID: 467567 [Multi-domain] Cd Length: 140 Bit Score: 37.60 E-value: 8.60e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 537924563  44 GAVAVLVVHVGKILLVRQYRKAieahtLEIPAGKLDHdGESPLEAAKRELEEE 96
Cdd:cd04684   17 GAYAVIFNDEGKVLLVQTPNGG-----YFLPGGGIEP-GETPEEALHREVLEE 63

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

Pssm-ID: 467562 [Multi-domain] Cd Length: 126 Bit Score: 37.67 E-value: 9.09e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 537924563  54 GKILLVRQyRKAIEAHTLEIPAGKLDHdGESPLEAAKRELEEEAQLS 100
Cdd:cd04679   13 GRLLLVLR-LRAPEAGHWGLPGGKVDW-LETVEDAVRREILEELGLE 57

RNA pyrophosphohydrolase; Reviewed

Pssm-ID: 234820 [Multi-domain] Cd Length: 156 Bit Score: 37.83 E-value: 9.59e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 537924563  47 AVLVVHVGKILLVRQYRkaiEAHTLEIPAGKLDhDGESPLEAAKRELEEE 96
Cdd:PRK00714  13 IILLNRQGQVFWGRRIG---QGHSWQFPQGGID-PGETPEQAMYRELYEE 58

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

Pssm-ID: 467547 Cd Length: 147 Bit Score: 37.17 E-value: 1.43e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  43 NGAVAVLVVHVGKILLVRQyrkaiEAHTLEIPAGkLDHDGESPLEAAKRELEEEAQLSANEwkKVVDL--VPTPGycNEK 120
Cdd:cd04662   12 DGGLEVLLVHPGGPFWARK-----DEGAWSIPKG-EVEPGEDPLAAARREFEEETGFPAPG--PFIPLgeVRQKS--GKV 81

                         90       100       110
                 ....*....|....*....|....*....|....
gi 537924563 121 IHLYEAKGiqhlenaaPLDEDEFVS----IEWIP 150
Cdd:cd04662   82 VHAWAVEG--------DLDPAAIVSntfeLEWPP 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.

Pssm-ID: 467578 [Multi-domain] Cd Length: 157 Bit Score: 37.21 E-value: 1.84e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 537924563  82 GESPLEAAKRELEEEAQLSANEWKKVVDLVPTPGYCNEKIHLYEAKgiqhLENAAPLDEDEFVSIEWIPVEEVIQ 156
Cdd:cd04697   67 GESYEENARRELEEELGIDGVPLRPLFTFYYEDDRSRVWGALFECV----YDGPLKLQPEEVAEVDWMSEDEILQ 137

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 37.68 E-value: 2.28e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 537924563  49 LVVHVGKILLVRqyRKAIEAHTL-EIPAGKLDHDgESPLEAAKRELEEEAQL 99
Cdd:PRK05379 209 VVVQSGHVLLVR--RRAEPGKGLwALPGGFLEQD-ETLLDACLRELREETGL 257

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

Pssm-ID: 467591 [Multi-domain] Cd Length: 126 Bit Score: 35.97 E-value: 3.01e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  45 AVAVLVVHVGKILLVRqYRKAIEAHTLeIPAGKLDHdGESPLEAAKRELEEEAQLSAnewkKVVDLVptpgYCNEKIHLY 124
Cdd:cd18880    3 RAKAIIIEDGKLLLVK-HRDEGGIFYI-LPGGGQEH-GETLPEALKRECLEETGLDV----EVGDLL----FVREYIGPN 71

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 537924563 125 eaKGIQHLE---------NAAPLDEDE---FVSIEWIPVEEVIQ 156
Cdd:cd18880   72 --KPVHQVElfflctlegGELTLGSDPdlnQVGVEWIPLEELDS 113

nudix hydrolase

Pssm-ID: 215184 [Multi-domain] Cd Length: 144 Bit Score: 36.38 E-value: 3.10e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 537924563  45 AVAVLVVHVGKILLVRQyRKAIEAHTLEIPAGKLDHdGESPLEAAKRELEEEAQLSANEWK 105
Cdd:PLN02325  11 AVVVFLLKGNSVLLGRR-RSSIGDSTFALPGGHLEF-GESFEECAAREVKEETGLEIEKIE 69

diadenosine tetraphosphate; Diadenosine tetraphosphate (Ap4A; EC 3.6.1.17), also called NUDIX (nucleoside diphosphate-linked moiety X)) motif 2/Nudt2, is a member of the NUDIX hydrolase superfamily. Ap4A hydrolases are well represented in a variety of prokaryotic and eukaryotic organisms. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one subfamily and fungi/animals/archaea enzymes, represented by this subfamily, fall into another. Bacterial enzymes are found in both subfamilies. Ap4A is a potential by-product of aminoacyl tRNA synthesis, and accumulation of Ap4A has been implicated in a range of biological events, such as DNA replication, cellular differentiation, heat shock, metabolic stress, and apoptosis. Ap4A hydrolase cleaves Ap4A asymmetrically into ATP and AMP. It is important in the invasive properties of bacteria and thus presents a potential target for inhibition of such invasive bacteria. Besides the signature NUDIX motif (G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val) that functions as a metal binding and catalytic site, and a required divalent cation, Ap4A hydrolase is structurally similar to the other members of the NUDIX hydrolase superfamily with some degree of variation. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies.

Pssm-ID: 467534 [Multi-domain] Cd Length: 132 Bit Score: 35.61 E-value: 4.05e-03

                         10        20        30
                 ....*....|....*....|....*....|
gi 537924563  74 PAGKLDhDGESPLEAAKRELEEEAQLSANE 103
Cdd:cd03428   33 PKGHVE-PGESELETALRETKEETGLTVDD 61

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

Pssm-ID: 467545 [Multi-domain] Cd Length: 123 Bit Score: 35.63 E-value: 4.07e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 537924563  46 VAVLVVHVGKILLVRqyrKAIEAH----TLeiPAGKLDhDGESPLEAAKRELEEEAQLSAN 102
Cdd:cd04511    5 VGCLPEWEGKVLLCR---RAIEPRkgywTL--PAGFME-LGETTEQGAARETREEAGARVE 59

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

Pssm-ID: 467563 [Multi-domain] Cd Length: 121 Bit Score: 35.69 E-value: 4.08e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  44 GAVAVLVVHVGKILLVRqyrkaieaHTL----EIPAGKLDHdGESPLEAAKRELEEEAQLSANEWKKVVDLvptpgYCNE 119
Cdd:cd04680    2 GVRAIVLDDAGRVLLVR--------HTYvpgwYLPGGGVDK-GETAEEAARRELREEAGVVLTGPPRLFGV-----YFNR 67

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 537924563 120 KIH------LYEAKGIQHLENAAPLdeDEFVSIEWIP 150
Cdd:cd04680   68 RVSprdhvaLYRVREFEQTEPPEPN--GEIAEAGFFA 102

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

Pssm-ID: 467532 [Multi-domain] Cd Length: 158 Bit Score: 35.93 E-value: 4.87e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537924563  45 AVAVLVVHVGK---ILLVRqyRKA-IEAHTLEI--PAGKLDHDGESPLEAAKRELEEEAQLSANE---WKKVVDLVPTPG 115
Cdd:cd03426    4 AVLIPLVEGDGelhVLLTK--RAShLRSHPGQIafPGGKREPGDESPVETALRETEEEIGLPPESvevLGRLDPLYTPSG 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 537924563 116 YcneKIH--LyeakGIQHLENAAPLDEDEFVSIEWIPVEE 153
Cdd:cd03426   82 F---VVTpfV----GLLDDPPPLRPNPDEVAEVFTVPLSF 114

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

Pssm-ID: 182536 [Multi-domain] Cd Length: 135 Bit Score: 35.10 E-value: 7.54e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 537924563  46 VAVLVVHVGKILLVRQYRKAIEAHTLEIPAGKLDhDGESPLEAAKRELEEEAQLSA 101
Cdd:PRK10546   7 VAAIIERDGKILLAQRPAHSDQAGLWEFAGGKVE-PGESQPQALIRELREELGIEA 61

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

Pssm-ID: 467568 [Multi-domain] Cd Length: 138 Bit Score: 34.86 E-value: 8.00e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 537924563  45 AVAVLVV-HVGKILLVR-QYRKAIEAHTLEIPAGKLDHdGESPLEAAKRELEEE 96
Cdd:cd04685    2 AARVLLLdPDGRVLLFRfHDPDDPGRSWWFTPGGGVEP-GESPEQAAVRELREE 54