NCBI Conserved Domain Search

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

Pssm-ID: 467540 Cd Length: 144 Bit Score: 239.76 E-value: 7.04e-77

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  96 VPVCGAIILNDAMDKCILVKGWTARSGWGFPKGKINKDEPDASCAVREVWEETGFDATEKIRDEDFVEQTIKDQRIRLYI 175
Cdd:cd03672     1 VPVRGAILLNEDLDKVLLVKGWKSNSSWGFPKGKINKDESDADCAIREVYEETGFDISDLINDKDYIELTINGQRVRLYI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079 176 IKSVSENTVFEPQTRKEISKIEWHYIADLPTSKpkpiekgthsgresgterSNGIKNPSRYYMVTPFVHKLKNWIITQRR 255
Cdd:cd03672    81 IPGVPEDTPFEPQTRKEISKIEWFDIDDLPKNK------------------KKKGKNSNKFYMVNPFVKPLKKWIKKRKQ 142


                  ..
gi 1936086079 256 SN 257
Cdd:cd03672   143 KK 144

Dcp2, box A domain; This domain is always found to the amino terminal side of pfam00293. This domain is specific to mRNA decapping protein 2 and this region has been termed Box A. Removal of the cap structure is catalyzed by the Dcp1-Dcp2 complex.

Pssm-ID: 428265 Cd Length: 83 Bit Score: 163.07 E-value: 1.45e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  10 HVLDDLSSRFIINVPDEELASVERICFQIEQAHWFYEDFIREQNPSLPSFNLKSFSAKFFQHCPLLHEWANEHETAFANF 89
Cdd:pfam05026   1 EILDDLCVRFIINLPEEELSSFERLFFQIEEAHWFYEDFVREDNPSLPSLSLKEFAELIFHHCPLLSKWDDDIDEALAEF 80


                  ...
gi 1936086079  90 MEY 92
Cdd:pfam05026  81 KEY 83

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: 71.99 E-value: 5.79e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  90 MEYKIRVPVCGAIILNDAmDKCILVKGWTARSG---WGFPKGKINKDEPDASCAVREVWEETGFDATEKIRDEDFVEQTI 166
Cdd:COG0494     7 SEPEHYRPAVVVVLLDDD-GRVLLVRRYRYGVGpglWEFPGGKIEPGESPEEAALRELREETGLTAEDLELLGELPSPGY 85

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1936086079 167 KDQRIRLYIIKSVSENTVFEPQTRKEISKIEWHYIADLP 205
Cdd:COG0494    86 TDEKVHVFLARGLGPGEEVGLDDEDEFIEVRWVPLDEAL 124

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 63.84 E-value: 2.65e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  90 MEYKIRVpVCGAIILNDAmDKCILVK-GWTARSG-WGFPKGKINKDEPDASCAVREVWEETGFDATE----KIRDEDFVE 163
Cdd:COG1051     1 MTKVPKV-AVDAVIFRKD-GRVLLVRrADEPGKGlWALPGGKVEPGETPEEAALRELREETGLEVEVlellGVFDHPDRG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1936086079 164 QTIkdqrIRLYIIKSVSEntvfEPQTRKEISKIEWHYIADLP 205
Cdd:COG1051    79 HVV----SVAFLAEVLSG----EPRADDEIDEARWFPLDELP 112

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: 62.42 E-value: 5.49e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  97 PVCGAIILNDAmDKCILVK--GWTARSGWGFPKGKINKDEPDASCAVREVWEETGFDAT---EKIRDEDFVEQTIKDQRI 171
Cdd:cd02883     1 VAVGAVVFDDE-GRVLLVRrsDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEvlrLLGVYEFPDPDEGRHVVV 79

                          90       100
                  ....*....|....*....|....*..
gi 1936086079 172 RLYIIKSVSENTVFEPQTrkEISKIEW 198
Cdd:cd02883    80 LVFLARVVGGEPPPLDDE--EISEVRW 104

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 62.89 E-value: 8.11e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079 100 GAIILNDAmDKCILVKGW--TARSGWGFPKGKINKDEPDASCAVREVWEETGFDA-----TEKIRDEDFVEQTIKDQRIR 172
Cdd:pfam00293   7 GVVLLNEK-GRVLLVRRSkkPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPellelLGSLHYLAPFDGRFPDEHEI 85

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1936086079 173 LYIIKSVSENTVfEPQTRKEISKIEWHYIADLP 205
Cdd:pfam00293  86 LYVFLAEVEGEL-EPDPDGEVEEVRWVPLEELL 117

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: 59.10 E-value: 1.40e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079 122 GWGFPKGKINKDEPDASCAVREVWEETGFDAtEKIRDEDFVEQTIKDQRIRlyIIKSV------SENTVFEPQTRKEISK 195
Cdd:cd03673    28 DWSLPKGKLEPGETPEEAAVREVEEETGLRV-RLGRPLGTTRYTYTRKGKG--ILKKVhywlmrALGGEFLPQPEEEIDE 104


                  ...
gi 1936086079 196 IEW 198
Cdd:cd03673   105 VRW 107

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: 58.72 E-value: 2.05e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  99 CGAIILNDAMDKC--ILVKgwTARSG-WGFPKGKINKDEPDASCAVREVWEETGFdaTEKIRDEDFVE------QTIKDQ 169
Cdd:cd03428     5 AGAIIYRRDNGEIefLLLQ--HSYGGhWDFPKGHVEPGESELETALRETKEETGL--TVDDLPPGFREtltysfKEGVEK 80

                          90       100
                  ....*....|....*....|....*....
gi 1936086079 170 RIRLYIIKSVSENTVfepQTRKEISKIEW 198
Cdd:cd03428    81 TVVYFLAELTPDVEV---KLSEEHQDYKW 106

Antisense Basic Fibroblast Growth Factor; Antisense Basic Fibroblast Growth Factor (ASFGF2; EC 3.6.1.-), also known as nucleoside diphosphate-linked moiety X)) motif 6/Nudt6, and similar proteins including peroxisomal coenzyme A diphosphatase/Nudt7 and mitochondrial coenzyme A diphosphatase/Nudt8. The Nudt6 gene overlaps and lies on the opposite strand from FGF2 gene, and is thought to be the FGF2 antisense gene. The two genes are independently transcribed, and their expression shows an inverse relationship, suggesting that this antisense transcript may regulate FGF2 expression. This gene has also been shown to have hormone-regulatory and antiproliferative actions in the pituitary that are independent of FGF2 expression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467554 [Multi-domain] Cd Length: 131 Bit Score: 52.15 E-value: 3.78e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1936086079  99 CGAIILNDamDKCILV---KGWTaRSGWGFPKGKINKDEPDASCAVREVWEETGFDA 152
Cdd:cd04670     5 VGGLVINE--NNEVLVvqeKYGG-PGGWKLPGGLVDPGEDIGEAAVREVFEETGIDT 58

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: 48.22 E-value: 6.94e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  96 VPVCGAIILNDamDKcILVkgwTARS-------GWGFPKGKINKDEPDASCAVREVWEETGFDatekIRDEDFVEQTI-- 166
Cdd:cd03425     1 IEVVAAIIVDD--GR-VLI---AQRPegkhlagLWEFPGGKVEPGETPEQALVRELREELGIE----VEVGEPLGTVEhd 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1936086079 167 -KDQRIRL--YIIKSVSEntvfEPQTRkEISKIEWHYIADLPT 206
Cdd:cd03425    71 yPDFHVRLhvYLCTLWSG----EPQLL-EHQELRWVTPEELDD 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: 467586 [Multi-domain] Cd Length: 125 Bit Score: 48.44 E-value: 7.41e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1936086079  96 VPVCGAIILNDAmDKCILVKGWTARSGWGFPKGKINKDEPDASCAVREVWEETGFDAT--------EKIRDEDF 161
Cdd:cd18874     2 EPTVGALIFNPD-GKVLLVRSHKWNDLYGIPGGKVEWGETLEEALKREVKEETGLDITdirfilvqESINSEEF 74

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: 47.56 E-value: 1.58e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  94 IRVPVcGAIILNDamDKCILV---KGWTARSGWGFPKGKINKDEPDASCAVREVWEETGFDatekIRDEDF--VEQTIKD 168
Cdd:cd04678     1 PRVGV-GVIVLND--DGKVLLgrrKGSHGAGTWALPGGHLEFGESFEECAAREVLEETGLE----IRNVRFltVTNDVFE 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1936086079 169 QRIRLYIiksvsenTVF--------EPQTRKEISKIE---WHYIADLPTSKP--KPIEK 214
Cdd:cd04678    74 EEGKHYV-------TIFvlaevddgEPEENMEPDKCEgweWFSWDELPPLRPlfLPLAN 125

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: 45.97 E-value: 6.01e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1936086079 100 GAIILNDamDKCILVK-------GWtarsgWGFPKGKINKDEPDASCAVREVWEETGFDAT 153
Cdd:cd04673     5 GAVVFRD--GRVLLVRrgnppdaGL-----WSFPGGKVELGETLEDAALRELREETGLEAE 58

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: 45.58 E-value: 8.34e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1936086079 101 AIILNDAMDKCILVKGW---TARSGWGFPKGKINKDEPDASCAVREVWEETGFDATE 154
Cdd:cd03424     6 AVLAITDDGKVVLVRQYrhpVGRVLLELPAGKIDPGEDPEEAARRELEEETGYTAGD 62

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: 45.38 E-value: 8.84e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  99 CGAIILNDamDKCILVKGWTA--RSGWGFPKGKINKDEPDASCAVREVWEETGFDatekIRDEDF---VEQTIKDQRIR- 172
Cdd:cd04679     5 CGAAILDD--GRLLLVLRLRApeAGHWGLPGGKVDWLETVEDAVRREILEELGLE----IELTRLlcvVDQIDAADGEHw 78

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1936086079 173 ---LYIIKSVS-ENTVFEPQtrkEISKIEWHYIADLPT 206
Cdd:cd04679    79 vapVYLAEIFSgEPRLMEPE---KHGGIGWFALDALPQ 113

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

Pssm-ID: 467559 [Multi-domain] Cd Length: 144 Bit Score: 44.70 E-value: 1.98e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1936086079  94 IRVPVCGAIILNDamDKCILVKGWTARSGWGFPKGKINKDEPDASCAVREVWEETG 149
Cdd:cd04676    15 LFTPSVAAVILNE--DGRILLQRKGGLGLWSLPAGAIEPGEHPAEAVIREVREETG 68

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: 43.73 E-value: 3.13e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1936086079  98 VCGAIILNDAMDKCILVKGwTARSGWGFPKGKINKDEPDASCAVREVWEETGFDAT 153
Cdd:cd18876     1 AAAGALFTDAAGRVLLVKP-TYKDGWELPGGVVEAGESPLQAARREVREELGLDVP 55

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: 43.43 E-value: 3.61e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079 109 DKCILVKGwtARSGWGFPKGKINKDEPDASCAVREVWEETGFDATEKIRDEDFveqtikDQRIRLYIIKSVSENTVFEPQ 188
Cdd:cd04667    11 DRILLVAR--RGGRWLLPGGKIEPGESPLEAAIRELKEETGLAALSLLYLFEH------EGPHKLHHVFLAEAPDGGRPR 82

                          90       100       110
                  ....*....|....*....|....*....|
gi 1936086079 189 TRKEISKIEWHYIADLPTSKPKPIEKGTHS 218
Cdd:cd04667    83 PGNEIARCRWVSADQLRDLNLSRATRLIVR 112

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: 43.39 E-value: 3.71e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1936086079 109 DKCILVKGwTARSGWGFPKGKINKDEPDASCAVREVWEETG 149
Cdd:cd04665    11 GKWLFTRH-KERRGWEFPGGKREPGETIEEAARRELYEETG 50

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: 43.29 E-value: 3.83e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  98 VCGAIILNDamDKCILV-KGWTARsgWGFPKGKINKDEPDASCAVREVWEETGFDatekirdedfveqtIKDQRIR-LYI 175
Cdd:cd04690     3 KAAVIIIKD--GRLLLVrKRGTDA--FYLPGGKREPGETPLQALVRELKEELGLD--------------LDPDSLRfLGT 64

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1936086079 176 IKSVSEN--------TVF------EPQTRKEISKIEW 198
Cdd:cd04690    65 FEAPAANepgttvrmTCFtadydgEPQPAAEIEELRW 101

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: 43.00 E-value: 4.57e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1936086079 101 AIILNDamDKCILVKGWTARSG-WGFPKGKINKDEPDASCAVREVWEETGFD 151
Cdd:cd04699     7 GVIFDN--GRVLLLRRSRAGAGeWELPGGRLEPGESPEEALKREVKEETGLD 56

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: 467587 [Multi-domain] Cd Length: 144 Bit Score: 42.94 E-value: 7.40e-05

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1936086079 120 RSGWGFPKGKINKDEPDASCAVREVWEETGFD 151
Cdd:cd18875    26 WGGYTFPGGHVEPGESFVDSVIREVKEETGLT 57

nucleoside diphosphate-linked moiety X)) motif 17; Nucleoside diphosphate-linked moiety X)) motif 17 (EC 3.6.1.-) encoded by the NUDT17 gene on chromosome 1q21.1 and encodes an enzyme thought to hydrolyse some nucleoside diphosphate derivatives. 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: 467576 [Multi-domain] Cd Length: 135 Bit Score: 42.28 E-value: 1.12e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  94 IRVPVCGAIIlndAMDKCILVkgwTARSG--------WGFPKGKINKDEPDASCAVREVWEETG--FDATEKIRDEDFVE 163
Cdd:cd04694     1 VDVGVVVLIE---DSDDRVLL---TRRAKhmrtfpgvWVPPGGHVELGESLLEAGLRELQEETGleVSDIQSLSLLGLWE 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1936086079 164 QTI---------KDQRIRLYIIKSVSENTVFEPQ---TRKEISKIEW 198
Cdd:cd04694    75 SVYptllsiglpKRHHIVVYYLVKLSESHENQEQlklQEDEVDAAVW 121

DR1025 and similar proteins; DR1025 from Deinococcus radiodurans, a member of the NUDIX hydrolase superfamily, show nucleoside triphosphatase and dinucleoside polyphosphate pyrophosphatase activities. Like other enzymes belonging to this superfamily, it requires a divalent cation, in this case Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. In general, substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

Pssm-ID: 467580 [Multi-domain] Cd Length: 147 Bit Score: 42.59 E-value: 1.13e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  90 MEYKIR--VPV----CGAIILNDAMDKCIL----VKGWTARSG-WGFPKGKINKDEPDASCAVREVWEETGFdateKIRD 158
Cdd:cd04700     1 MQHGERthVPVtlraAGVVLLNERGDILLVqekgISGHPEKAGlWHIPSGAVEDGENPQDAAVREACEETGL----RVRL 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1936086079 159 EDFVEQTI-----KDQRIRLYIIKSVSENTVFEPQTRKEISKIEWHYIADL 204
Cdd:cd04700    77 VKFLGAYLgrfpdGVLVLRHVWLAEPEPGQVLAPAFTDEIAEASFVSREEF 127

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.

Pssm-ID: 467551 [Multi-domain] Cd Length: 128 Bit Score: 42.13 E-value: 1.20e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1936086079  97 PVCGAI--ILNDAMDKCILVkgwTARSG--WGFPKGKINKDEPDASCAVREVWEETG 149
Cdd:cd04666     1 LQAGALpyRITKGELEVLLI---TSRKTgrWILPKGGPEKGETPAEAAAREAWEEAG 54

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: 41.86 E-value: 1.43e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1936086079  98 VCGAIILNDAMDKCILVKGWTARSgWGFPKGKINKDE-PDAsCAVREVWEETGFDAT 153
Cdd:cd03674     3 TASAFVVNPDRGKVLLVHHRKLGR-WLQPGGHVEPDEdPLE-AALREAREETGLDVE 57

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: 41.78 E-value: 1.86e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1936086079 100 GAIILNDamDKCILvkgWTARSG----WGFPKGKINKDEPDASCAVREVWEETGFDAT-----EKIRDE 159
Cdd:cd03671     7 GIVLFNR--DGQVL---VGRRIDvpgaWQFPQGGIDEGEDPEEAALRELYEETGLSPEdveiiAETPDW 70

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: 41.47 E-value: 1.86e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079 101 AIILNDAmDKCILVKGwTARSGWGFPKGKINKDEPDASCAVREVWEETGFDATEKIR--DEDFVEQTIKDQRIRLYIIKS 178
Cdd:cd04680     5 AIVLDDA-GRVLLVRH-TYVPGWYLPGGGVDKGETAEEAARRELREEAGVVLTGPPRlfGVYFNRRVSPRDHVALYRVRE 82

                          90       100
                  ....*....|....*....|....*..
gi 1936086079 179 VSENTVFEPQtrKEISKIEWHYIADLP 205
Cdd:cd04680    83 FEQTEPPEPN--GEIAEAGFFALDALP 107

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: 40.31 E-value: 6.17e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1936086079 109 DKCILVKGWTA---RSGWGFPKGKINKDEPDASCAVREVWEETGFDATE 154
Cdd:cd24156    14 DHLLLIREYAAgteRYELGFPKGLIDPGETPEEAANRELKEEIGFGARQ 62

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: 40.25 E-value: 7.06e-04

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1936086079 120 RSGWGFPKGKINKDEPDASCAVREVWEETGFDA 152
Cdd:cd04662    32 EGAWSIPKGEVEPGEDPLAAARREFEEETGFPA 64

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: 39.82 E-value: 8.53e-04

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1936086079 124 GFPKGKIN----KDEPDAS---CAVREVWEETGFDATE 154
Cdd:cd03427    23 GFGAGKWNgfggKVEPGETieeAAVRELEEEAGLTATE 60

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: 40.44 E-value: 9.32e-04

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1936086079 119 ARSGWGFPKGKINKDEPDASCAVREVWEETGFDATE 154
Cdd:cd24159    66 KRVFLEFPAGKIDPGEDTLETAKRELLEETGYEAQE 101

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: 38.88 E-value: 1.68e-03

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1936086079 116 GWTARSG-WGFPKGKINKDEPDASCAVREVWEETGFDA 152
Cdd:cd18877    41 WWTHQGGtWALPGGARDSGETPEAAALRETEEETGLDA 78

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

Pssm-ID: 443295 [Multi-domain] Cd Length: 153 Bit Score: 39.04 E-value: 2.01e-03

                          10        20        30
                  ....*....|....*....|....*....|
gi 1936086079 123 WGFPKGKINKDEPDASCAVREVWEETGFDA 152
Cdd:COG4119    38 WSIPKGEYEPGEDPLAAARREFAEETGVPA 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.

Pssm-ID: 467560 [Multi-domain] Cd Length: 137 Bit Score: 38.65 E-value: 2.16e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1936086079  97 PVCGAIILNDAmDKCILVKgwtaRS---GWGFPKGKINKDEPDASCAVREVWEETGFDA 152
Cdd:cd04677    13 VGAAVIILNEQ-GRILLQK----RTdtgDWGLPGGAMELGESLEETARREVFEETGLTV 66

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: 38.28 E-value: 2.60e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1936086079  99 CGAIILNDamDKCILVKGWTARSG-WGFPKGKINKDEPDASCAVREVWEETGFD 151
Cdd:cd18880     4 AKAIIIED--GKLLLVKHRDEGGIfYILPGGGQEHGETLPEALKRECLEETGLD 55

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: 37.62 E-value: 4.16e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1936086079 123 WGFPKGKINKDEPDASCAVREVWEETGFDATEkIRDEDFVEQTIKDQRIR 172
Cdd:cd18882    32 WGLFGGHLEPGETPEEAIRRELEEEIGYEPGE-FRFFLLYTEDDGEDRIR 80

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: 37.99 E-value: 4.17e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  91 EYKIRvPVCGAIILNDAmDKCILVKgwTARSGWGFPKGKINKDEPDASCAVREVWEETGF 150
Cdd:cd04684    11 NYKDR-PGAYAVIFNDE-GKVLLVQ--TPNGGYFLPGGGIEPGETPEEALHREVLEETGW 66

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: 36.89 E-value: 6.43e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  98 VCGAIILNDamdKCILVK---GwTARSGWGFPKGKINKDEPDASCAVREVWEETGFDATEK----IRDEdfVEQTIKDQR 170
Cdd:cd04691     4 VGGVVVKEG---KVLLVKrayG-PGKGRWTLPGGFVEEGETLDEAIVREVLEETGIDAKPVgiigVRSG--VIRDGKSDN 77

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1936086079 171 IRLYIIKSVSENTvfEPQTRkEISKIEWHYIADL 204
Cdd:cd04691    78 YVVFLLEYVGGEP--KPDER-ENSEAGFLTLEEA 108

dihydroneopterin triphosphate pyrophosphatase; Provisional

Pssm-ID: 236516 [Multi-domain] Cd Length: 148 Bit Score: 37.57 E-value: 6.77e-03

                          10        20
                  ....*....|....*....|....*.
gi 1936086079 128 GKINKDEPDASCAVREVWEETGFDAT 153
Cdd:PRK09438   38 GSLEEGETPAQTAIREVKEETGIDVL 63

RNA pyrophosphohydrolase; Reviewed

Pssm-ID: 234820 [Multi-domain] Cd Length: 156 Bit Score: 37.06 E-value: 8.69e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1936086079 100 GAIILNDamdkcilvKG---WTARSG----WGFPKGKINKDEPDASCAVREVWEETG 149
Cdd:PRK00714   12 GIILLNR--------QGqvfWGRRIGqghsWQFPQGGIDPGETPEQAMYRELYEEVG 60

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: 467570 [Multi-domain] Cd Length: 130 Bit Score: 36.37 E-value: 9.91e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1936086079  92 YKIRVpvcGAIILNDamdKCILVKGWTARSGWGFPKGKINKDEPDASCAVREVWEETGfdatekirdedfveqtIKDQRI 171
Cdd:cd04688     1 FNIRV---AAIIIRD---GKVLLARGEDDDYYRLPGGRVEFGETSEDALVREFKEELG----------------VEVEVV 58

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1936086079 172 RLyiiKSVSENT-VFEPQTRKEiskIEWHYIADLPTskPKPIEKGTHSGRESGTE 225
Cdd:cd04688    59 RL---LFVVENFfTYDGKPFHE---IGFYYLVELSD--EALYEQDIFFLEEDGEK 105