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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  15 DVEIIARETLYSGFFSMDLYRFRHRLFNGEMSGEIRREIFERGHAAVLLPFDPVRDEVVLVEQIRIAAYDVSESPWLLEM 94
Cdd:cd24155     1 DVEILSKETVYDGFFRLERYRLRHRRFDGGWSAPLTREIFERGDAVAVLPYDPVRDEVVLIEQFRIGALARDESPWLLEI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  95 VAGMIEEGETVEDVARREALEEAGLVVGRTKPVLSYLASPGGTSERLSIMVGEVDATTAEGIHGLADENEDIRVHVVSRE 174
Cdd:cd24155    81 VAGMIDAGETPEDVARREAEEEAGLTLDALEPIASYYPSPGGSTERVHLYLGLVDLSDLGGIHGLAEEGEDIRVHVVPFD 160

                         170       180
                  ....*....|....*....|....*..
gi 1542754326 175 QAYQWVEEGKIDNAASVIALQWLQLHY 201
Cdd:cd24155   161 EAMALLDDGEIDNAPLIIALQWLALNR 187

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  45 MSGEIRREIFERGHAAVLLPFDPvRDEVVLVEQIRIAAYdvsesPWLLEMVAGMIEEGETVEDVARREALEEAGLVVGRT 124
Cdd:COG0494     1 MTEILSSEPEHYRPAVVVVLLDD-DGRVLLVRRYRYGVG-----PGLWEFPGGKIEPGESPEEAALRELREETGLTAEDL 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1542754326 125 KPVLSYLaSPGGTSERLSIMVGEVdaTTAEGIHGLADENEDIRVHVVSREQAYQWVEEGKIdnAASVIALQWLQ 198
Cdd:COG0494    75 ELLGELP-SPGYTDEKVHVFLARG--LGPGEEVGLDDEDEFIEVRWVPLDEALALVTAGEI--AKTLAALARLL 143

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  15 DVEIIARETLYSGFFSMDLYRFRHRLFNGEMSGEIRREIFERGHAAVLLPFDPVRDEVVLVEQIRIAAYDVSESPWLLEM 94
Cdd:cd24155     1 DVEILSKETVYDGFFRLERYRLRHRRFDGGWSAPLTREIFERGDAVAVLPYDPVRDEVVLIEQFRIGALARDESPWLLEI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  95 VAGMIEEGETVEDVARREALEEAGLVVGRTKPVLSYLASPGGTSERLSIMVGEVDATTAEGIHGLADENEDIRVHVVSRE 174
Cdd:cd24155    81 VAGMIDAGETPEDVARREAEEEAGLTLDALEPIASYYPSPGGSTERVHLYLGLVDLSDLGGIHGLAEEGEDIRVHVVPFD 160

                         170       180
                  ....*....|....*....|....*..
gi 1542754326 175 QAYQWVEEGKIDNAASVIALQWLQLHY 201
Cdd:cd24155   161 EAMALLDDGEIDNAPLIIALQWLALNR 187

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  54 FERGHAAVLLPFDPVRDEVVLVEQIRIAAYDVSESPWLLEMVAGMIeEGETVEDVARREALEEAGLVVGRTKPVLSYLAS 133
Cdd:cd24157     1 YDRGDAAAVLLYDPKRKTVVLVRQFRAPAYLGGGDGWLIEACAGLL-DGDDPEDCIRREAEEETGYRLGDLEKVFTAYSS 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1542754326 134 PGGTSERLSIMVGEVDAT--TAEGiHGLADENEDIRVHVVSREQAYQWVEEGKIDNAASVIALQWLQL 199
Cdd:cd24157    80 PGIVTERIHLFIAEYSSAdrVGAG-GGLAEEGEDIEVLELPLDEALAMIETGEIRDAKTIILLQYLRL 146

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  45 MSGEIRREIFERGHAAVLLPFDPvRDEVVLVEQIRIAAYdvsesPWLLEMVAGMIEEGETVEDVARREALEEAGLVVGRT 124
Cdd:COG0494     1 MTEILSSEPEHYRPAVVVVLLDD-DGRVLLVRRYRYGVG-----PGLWEFPGGKIEPGESPEEAALRELREETGLTAEDL 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1542754326 125 KPVLSYLaSPGGTSERLSIMVGEVdaTTAEGIHGLADENEDIRVHVVSREQAYQWVEEGKIdnAASVIALQWLQ 198
Cdd:COG0494    75 ELLGELP-SPGYTDEKVHVFLARG--LGPGEEVGLDDEDEFIEVRWVPLDEALALVTAGEI--AKTLAALARLL 143

ADP-ribose pyrophosphatase from Mycobacterium tuberculosis (Mt-ADPRase), and similar proteins; Mycobacterium tuberculosis ADP-ribose pyrophosphatase mt-ADPRase(also called Rv1700) is a NUDIX protein that catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  17 EIIARETLYSG-FFSMdlyrfRHRLFNGEMSGEIRREIFERGHAAVLLPFDPvRDEVVLVEQIRIAaydVSESPWllEMV 95
Cdd:cd24158     1 PVLSSEVVYEGaIWDV-----RRDTVDLPGGGTVTREYVEHPGAVAVVALDD-DGRVLLIRQYRHP---VRRRLW--ELP 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  96 AGMIE-EGETVEDVARREALEEAGLVVGRTKPVLSYLASPGGTSERLSIMVGE-VDATTAEGIHGLADENEDIRVHVVSR 173
Cdd:cd24158    70 AGLLDvAGEPPLEAAARELAEEADLEAARWEVLVDLFTSPGFSSEAVRVYLARgLSEVPEADRHEREDEEADMTLRWVPL 149

                         170       180
                  ....*....|....*....|.
gi 1542754326 174 EQAYQWVEEGKIDNAASVIAL 194
Cdd:cd24158   150 DEAVAAVLAGRITNSTAVAGV 170

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  70 DEVVLVEQIR--IAAYdvsespwLLEMVAGMIEEGETVEDVARREALEEAGLV---VGRTKPVLSYlaSPGGTSERLSIM 144
Cdd:cd18888    18 PELVLVKQYRppVNAY-------TIEFPAGLVDPGESPEQAALRELKEETGYTgekVLSVSPPLAL--DPGLSNANMKLV 88

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1542754326 145 VGEVDATTAEGIHGLA--DENEDIRVHVVSREQAYQWVEE 182
Cdd:cd18888    89 TVEVDGDDPENQNPKQelEDGEFIEVILVPLNELLERLQE 128

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  19 IARETLYSGFFsMDLYRFRHRLFNGEMSgeiRREIFERGHAAVLLPFDPvRDEVVLVEQIRIAAYDVsespwLLEMVAGM 98
Cdd:cd24159     7 LSSRVVYKGGF-LKVHRDQVRLPDGSTS---TREYITHPGAVAVVPLLD-DGRVVMERQYRYPLKRV-----FLEFPAGK 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  99 IEEGETVEDVARREALEEAGLV------VGRTKPVLSYlaspggTSERLSIMVgevdattAEGIHGLA---DENEDIRVH 169
Cdd:cd24159    77 IDPGEDTLETAKRELLEETGYEaqewafLTTIHPAIGY------SNEHIEIYL-------ARGLTHVEqklDDGEFLEVV 143

                         170       180
                  ....*....|....*....|....*....
gi 1542754326 170 VVSREQAYQWVEEGKIDNAASVIALQWLQ 198
Cdd:cd24159   144 EVSLAELLEMVLSGEITDVKTIIGLFWLQ 172

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  58 HAAVLLPFDPvRDEVVLVEQIRiaaydvSESPWLLEMVAGMIEEGETVEDVARREALEEAGLVVGRTKPVLSYLASPGGT 137
Cdd:cd02883     1 VAVGAVVFDD-EGRVLLVRRSD------GPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDE 73

                          90       100       110
                  ....*....|....*....|....*....|
gi 1542754326 138 SERLSIMVGEVDATTAEGIHGLADENEDIR 167
Cdd:cd02883    74 GRHVVVLVFLARVVGGEPPPLDDEEISEVR 103

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1542754326  95 VAGMIEEGETVEDVARREALEEAGLVVGRtkpvLSYLAS-----PGgtserlSIMVGEVDATTAEGIHGLADENEDIR 167
Cdd:cd03429    31 LAGFVEPGETLEEAVRREVKEEVGLRVKN----VRYVGSqpwpfPS------SLMLGFTAEADSGEITVDDDELEDAR 98

adenosine nucleotide hydrolase NudE; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326   2 QKPEKLpvtfaknDVEIIARetlySGFF---SMDLyRFRhrlfNGEmsgeirREIFER----GHAAVL-LPFDPvRDEVV 73
Cdd:PRK11762    6 QKPEIL-------NRETVAK----SRLFrveSVDL-EFS----NGV------ERVYERmrpsGRGAVMiVPILD-DDTLL 62

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  74 LVEQiriaaYDVSESPWLLEMVAGMIEEGETVEDVARREALEEAGLVVGRTKPVLSYLASPGGTSERLSIMVGEvD--AT 151
Cdd:PRK11762   63 LIRE-----YAAGTERYELGFPKGLIDPGETPLEAANRELKEEVGFGARQLTFLKELSLAPSYFSSKMNIVLAE-DlyPE 136

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1542754326 152 TAEGihglaDENEDIRVHVVSREQAYQWVEEGKIDNAASVIAL----QWLQ 198
Cdd:PRK11762  137 RLEG-----DEPEPLEVVRWPLADLDELLARPDFSEARSVAALflarEWLK 182

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1542754326  95 VAGMIEEGETVEDVARREALEEAGLVVGRtkpvLSYLAS-----PGgtserlSIMVG 146
Cdd:COG2816   187 LAGFVEPGETLEQAVRREVFEEVGVRVKN----VRYVGSqpwpfPS------SLMLG 233

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1542754326  56 RGHAAVLLPFDPvRDEVVLVEQIRIAAYDvsespwLLEMVAGMIEEGETVEDVARREALEEAGLVVGRTKPVLSY 130
Cdd:COG1051     5 PKVAVDAVIFRK-DGRVLLVRRADEPGKG------LWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVF 72

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1542754326  68 VRDEVVLVEQIRIAAYDvsESPWLLemVAGMIEEGETVEDVARREALEEAGLVV 121
Cdd:cd04683     8 VRGDEVLLLRRANTGYD--DGWWHL--PAGHVEAGETVRAAAVREAKEELGVEI 57

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

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1542754326  97 GMIEEGETVEDVARREALEEAGlVVGR--TKPVLSY 130
Cdd:cd04666    33 GGPEKGETPAEAAAREAWEEAG-VRGKvlKRPLGVY 67

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  59 AAVLLpFDPvRDEVVLVEqiriAAYdvsESPWLLemVAGMIEEGETVEDVARREALEEAGLVVGRTKP-VLSYLASPGGT 137
Cdd:cd18876     3 AGALF-TDA-AGRVLLVK----PTY---KDGWEL--PGGVVEAGESPLQAARREVREELGLDVPVGRLlAVDWVPPAGGG 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1542754326 138 SERLSIM--VGEVDATTAEGIHGlaDENEDIRVHVVSREQA 176
Cdd:cd18876    72 DDAVLFVfdGGVLTPEQAAAIRL--QDEELSAYRFVTPEEA 110

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

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1542754326  97 GMIEEGETVEDVARREALEEAGLVVGRTKPV 127
Cdd:cd04673    33 GKVELGETLEDAALRELREETGLEAEVVGLL 63

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1542754326  50 RREIFERG--HAAV-LLPFDPVRDEVVLveQIRIA-------AYDVSespwllemVAGMIEEGETVEDVARREALEEAGL 119
Cdd:cd04692    16 RSEVHRQGlwHRTVhVWLVNPEEGRLLL--QKRSAnkddfpgLWDIS--------AAGHIDAGETYEEAAVRELEEELGL 85

                  ..
gi 1542754326 120 VV 121
Cdd:cd04692    86 TV 87

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1542754326  58 HAAVLLPFDPvRDEVVLVEqiriAAYDVSESPWLLEMVAGMIEEGETVEDVARREALEEAGLVV 121
Cdd:cd04685     1 RAARVLLLDP-DGRVLLFR----FHDPDDPGRSWWFTPGGGVEPGESPEQAAVRELREETGLRL 59

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

                          10        20
                  ....*....|....*....|....*
gi 1542754326  97 GMIEEGETVEDVARREALEEAGLVV 121
Cdd:cd04678    35 GHLEFGESFEECAAREVLEETGLEI 59