NCBI Conserved Domain Search

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

Pssm-ID: 442065 [Multi-domain] Cd Length: 288 Bit Score: 306.84 E-value: 3.13e-102

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 119 NYFSRTLLDRRSDKRNNSDWLQAKeshPTTVYLLFSDLNPLVTLGGnkessqqPEVRLCQLNYPDvkgyLAQPEKitLVF 198
Cdd:COG2816   5 LAFAGSPLDRAAELRADPDWLAAW---ADPRVLVVDGGRLLLLEDG-------GELLLPAGEAAD----LGPPAE--AVF 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 199 LGvelemrkgspaqaggvpeeEEDGlVAWFALGIEPGAAEEfkQRHEncyfLHPPMPALLQLKEKEAGVVAQARSVLAWH 278
Cdd:COG2816  69 LG-------------------LDDG-RPVFAVDLPAELELP--EGAE----FVDLRELGGLLDPRDAGLAARAVALLNWH 122

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 279 SRYKFCPTCGSATKIEEGGYKRVCvrETCpslqgvHNTSYPRVDPVVIMQVIhpDGTKCLLGRQKRFPPGMFTCLAGFIE 358
Cdd:COG2816 123 RTHRFCGRCGAPTVVAAAGWARRC--PAC------GAEHYPRTDPAVIVLVT--DGDRILLARQARWPPGRYSLLAGFVE 192

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 359 PGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPSSLMIGCLAVAVSTEIKVDKNEIEDARWFTREQVVDVLTkgkqqA 438
Cdd:COG2816 193 PGETLEQAVRREVFEEVGVRVKNVRYVGSQPWPFPSSLMLGFTAEADSGEITVDGDEIEDARWFSRDELPAALA-----G 267

                       330
                ....*....|....*....
gi 21312664 439 FFVPPSRAIAHQLIKHWVG 457
Cdd:COG2816 268 LLLPPPGSIARRLIEAWLA 286

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

Pssm-ID: 467535 [Multi-domain] Cd Length: 126 Bit Score: 222.75 E-value: 7.18e-72

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 322 DPVVIMQVIHPDGtKCLLGRQKRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPSSLMIGCL 401
Cdd:cd03429   1 DPAVIVLVTNGED-KILLARQPRWPPGRYSLLAGFVEPGETLEEAVRREVKEEVGLRVKNVRYVGSQPWPFPSSLMLGFT 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 21312664 402 AVAVSTEIKVDKNEIEDARWFTREQVVDVLtkgkqqafFVPPSRAIAHQLIKHWV 456
Cdd:cd03429  80 AEADSGEITVDDDELEDARWFSRDELPEAL--------FLPPPGSIARRLIRAWL 126

NAD(+) diphosphatase;

Pssm-ID: 234699 [Multi-domain] Cd Length: 256 Bit Score: 199.69 E-value: 3.94e-61

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664  257 LLQLKEKEAGVVAQARSVLAWHSRYKFCPTCGSATKIEEGGYKRVCvrETCpslqgvHNTSYPRVDPVVIMqVIHpDGTK 336
Cdd:PRK00241  75 LLDLDDGLFQLLGRAVQLAEFYRSHRFCGYCGHPMHPSKTEWAMLC--PHC------RERYYPRIAPCIIV-AVR-RGDE 144

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664  337 CLLGRQKRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPSSLMIGCLAVAVSTEIKVDKNEI 416
Cdd:PRK00241 145 ILLARHPRHRNGVYTVLAGFVEVGETLEQCVAREVMEESGIKVKNLRYVGSQPWPFPHSLMLGFHADYDSGEIVFDPKEI 224

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 21312664  417 EDARWFTREQVVDvltkgkqqaffVPPSRAIAHQLIKHWV 456
Cdd:PRK00241 225 ADAQWFRYDELPL-----------LPPSGTIARRLIEDTV 253

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 75.98 E-value: 1.57e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664   329 VIHPDGTKCLLGRQ-KRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQ--------PWPMPSSLMIG 399
Cdd:pfam00293   9 VLLNEKGRVLLVRRsKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLhylapfdgRFPDEHEILYV 88

                          90       100
                  ....*....|....*....|....*....
gi 21312664   400 CLAVAVSTEIKVDKNEIEDARWFTREQVV 428
Cdd:pfam00293  89 FLAEVEGELEPDPDGEVEEVRWVPLEELL 117

Ankyrin repeat [Signal transduction mechanisms];

Pssm-ID: 440430 [Multi-domain] Cd Length: 289 Bit Score: 79.23 E-value: 2.34e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664  16 LHSSAAEGNVaKLAGILSHSPSLLNETSENGWTALMYAARNGHPDVVQFLLEKGCDRSLVNKARQTALDIAAFWGYRHIA 95
Cdd:COG0666 157 LHLAAANGNL-EIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIV 235

                        90
                ....*....|...
gi 21312664  96 NLLANAKGGKKPW 108
Cdd:COG0666 236 KLLLEAGADLNAK 248

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: 73.59 E-value: 5.54e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 329 VIHPDGTKCLLGRQKRFP-PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMP----SSLMIGCLAV 403
Cdd:cd02883   6 VVFDDEGRVLLVRRSDGPgPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPdegrHVVVLVFLAR 85

                        90       100
                ....*....|....*....|.
gi 21312664 404 AVSTEIKV-DKNEIEDARWFT 423
Cdd:cd02883  86 VVGGEPPPlDDEEISEVRWVP 106

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 73.47 E-value: 9.16e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 329 VIHPDGtKCLLGRQKRFP-PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPSS-LMIGCLAVAVS 406
Cdd:COG1051  13 IFRKDG-RVLLVRRADEPgKGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHPDRGHvVSVAFLAEVLS 91

                        90       100
                ....*....|....*....|.
gi 21312664 407 TEIKVDkNEIEDARWFTREQV 427
Cdd:COG1051  92 GEPRAD-DEIDEARWFPLDEL 111

Ankyrin repeat [Signal transduction mechanisms];

Pssm-ID: 440430 [Multi-domain] Cd Length: 289 Bit Score: 76.53 E-value: 1.98e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664  10 KEMISELHSSAAEGNVAKLAGILSHSPSLlNETSENGWTALMYAARNGHPDVVQFLLEKGCDRSLVNKARQTALDIAAFW 89
Cdd:COG0666  85 DGGNTLLHAAARNGDLEIVKLLLEAGADV-NARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAAN 163

                        90
                ....*....|...
gi 21312664  90 GYRHIANLLANAK 102
Cdd:COG0666 164 GNLEIVKLLLEAG 176

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: 71.22 E-value: 7.87e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 324 VVImqVIHPDGTKCLLGRQKRFP--PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWP-MPSSLMIGC 400
Cdd:COG0494  16 VVV--VLLDDDGRVLLVRRYRYGvgPGLWEFPGGKIEPGESPEEAALRELREETGLTAEDLELLGELPSPgYTDEKVHVF 93

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 21312664 401 LAVAVSTEIKV---DKNEIEDARWFTREQVVDVLTKGKQQA 438
Cdd:COG0494  94 LARGLGPGEEVgldDEDEFIEVRWVPLDEALALVTAGEIAK 134

Ankyrin repeat [Signal transduction mechanisms];

Pssm-ID: 440430 [Multi-domain] Cd Length: 289 Bit Score: 74.61 E-value: 7.90e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664  16 LHSSAAEGNVAKLAGILSHSPSLlNETSENGWTALMYAARNGHPDVVQFLLEKGCDRSLVNKARQTALDIAAFWGYRHIA 95
Cdd:COG0666 124 LHLAAYNGNLEIVKLLLEAGADV-NAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIV 202


                ....*..
gi 21312664  96 NLLANAK 102
Cdd:COG0666 203 KLLLEAG 209

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

Pssm-ID: 467595 [Multi-domain] Cd Length: 125 Bit Score: 65.13 E-value: 7.16e-13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 323 PVVIMQVIHPDGTkcLLGRQKRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPSSLMIGcLA 402
Cdd:cd18884  10 PVVAAIVEHDGHI--VLARNKAWPEGWYGLVTGFLEAGESPEEAVLREVKEELGLDGHEAKFIGHYAFPERNQLIIA-YH 86

                        90
                ....*....|....*.
gi 21312664 403 VAVSTEIKvDKNEIED 418
Cdd:cd18884  87 VRARGNVK-LNEELDD 101

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: 65.01 E-value: 8.80e-13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 348 GMFTCLAGFIEPGETIEDAVRREVEEESGV--KVGHVQYVSCQPWPMPSS-LMIGCLAVAVSTEIKVDKNEIEDARWFTR 424
Cdd:cd04691  26 GRWTLPGGFVEEGETLDEAIVREVLEETGIdaKPVGIIGVRSGVIRDGKSdNYVVFLLEYVGGEPKPDERENSEAGFLTL 105


                ....
gi 21312664 425 EQVV 428
Cdd:cd04691 106 EEAL 109

Ankyrin repeats (3 copies);

Pssm-ID: 463710 [Multi-domain] Cd Length: 91 Bit Score: 63.98 E-value: 9.40e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664    20 AAEGNVAKLAGILSHSPSLLNETSENGWTALMYAARNGHPDVVQFLLEKgCDRSLVNKaRQTALDIAAFWGYRHIANLLA 99
Cdd:pfam12796   4 AAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLEH-ADVNLKDN-GRTALHYAARSGHLEIVKLLL 81


                  .
gi 21312664   100 N 100
Cdd:pfam12796  82 E 82

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: 63.82 E-value: 2.17e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 329 VIHPDGTKCLLGR----QKRFPPGmftclaGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPW-----PMPSSLMIG 399
Cdd:cd03674   8 VVNPDRGKVLLVHhrklGRWLQPG------GHVEPDEDPLEAALREAREETGLDVELLSPLSPDPLdidvhPIPANPGEP 81

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 21312664 400 C--------LAVAVSTEIKVDKNEIEDARWFTREQV 427
Cdd:cd03674  82 AhlhldvryLAVADGDEALRKSDESSDVRWFPLDEL 117

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: 63.71 E-value: 3.17e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 329 VIHPDGtKCLLGRQKRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKvghVQYVSC----QPWPMP---SSLMIGCL 401
Cdd:cd04670   9 VINENN-EVLVVQEKYGGPGGWKLPGGLVDPGEDIGEAAVREVFEETGID---TEFVSIlgfrHQHPGRfgkSDLYFVCR 84

                        90       100
                ....*....|....*....|..
gi 21312664 402 AVAVS-TEIKVDKNEIEDARWF 422
Cdd:cd04670  85 LRPLSdEEIKICPEEIAEAKWM 106

Ankyrin repeat [Signal transduction mechanisms];

Pssm-ID: 440430 [Multi-domain] Cd Length: 289 Bit Score: 66.52 E-value: 5.15e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664   7 NPKKEMISELHSSAAEGNVAKLAGILSHSPSLLNETSENGWTALMYAARNGHPDVVQFLLEKGCDRSLVNKARQTALDIA 86
Cdd:COG0666  48 ALADALGALLLLAAALAGDLLVALLLLAAGADINAKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLA 127

                        90
                ....*....|....*
gi 21312664  87 AFWGYRHIANLLANA 101
Cdd:COG0666 128 AYNGNLEIVKLLLEA 142

Ankyrin repeats (many copies);

Pssm-ID: 433530 [Multi-domain] Cd Length: 56 Bit Score: 57.74 E-value: 5.77e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 21312664    31 ILSHSPSLLNETSENGWTALMYAARNGHPDVVQFLLEKGCDRSLVNKARQTALDIA 86
Cdd:pfam13857   1 LLEHGPIDLNRLDGEGYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 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: 467593 [Multi-domain] Cd Length: 130 Bit Score: 59.58 E-value: 8.06e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 347 PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPSSLMIGCLAVAVSTEI-KVDKNEIEDARWFTRE 425
Cdd:cd18882  29 PGYWGLFGGHLEPGETPEEAIRRELEEEIGYEPGEFRFFLLYTEDDGEDRIRHVFHAPLDVDLsDLVLNEGQALRLFSPE 108


                ....
gi 21312664 426 QVVD 429
Cdd:cd18882 109 EILQ 112

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: 59.47 E-value: 8.47e-11

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 21312664 333 DGTKCLLGRQKR-FPPGMFTCLAGFIEPGETIEDAVRREVEEESGV------KVGHVQYV-SCQPWPM 392
Cdd:cd03427  11 GDDRVLLGLKKRgFGAGKWNGFGGKVEPGETIEEAAVRELEEEAGLtateleKVGRLKFEfPDDPEAM 78

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: 59.44 E-value: 9.61e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 324 VVIMqVIHPDGtKCLLGRQKRFPPGMFTcL---AGFIEPGETIEDAVRREVEEESGVKVGHVQYVsCQPWPMP---SSLM 397
Cdd:cd03424   5 VAVL-AITDDG-KVVLVRQYRHPVGRVL-LelpAGKIDPGEDPEEAARRELEEETGYTAGDLELL-GSFYPSPgfsDERI 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 21312664 398 IGCLA--VAVSTEIKVDKNEIEDARWFTREQVVDVLTKGK 435
Cdd:cd03424  81 HLFLAedLTPVSEQALDEDEFIEVVLVPLEEALEMIEDGE 120

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

Pssm-ID: 441052 [Multi-domain] Cd Length: 162 Bit Score: 59.44 E-value: 1.71e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 329 VIHPDGtKCLLGR---QKRFPPGMFTCL-AGFIEPGETIEDAVRREVEEESGV-------KVGHVQYVScqpwPMPSSLM 397
Cdd:COG1443  36 VFNSDG-RLLLQRralTKDHWPGLWDNTvCGHPRAGETYEEAAVRELEEELGItvdddlrPLGTFRYRA----VDANGLV 110

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 21312664 398 ----IGCLAVAVSTEIKVDKNEIEDARWFTREQVVDVLTKGKQQafFVPPSRAI 447
Cdd:COG1443 111 enefCHVFVARLDGPLTPQPEEVAEVRWVTLEELLALLEAGPEA--FTPWFRLY 162

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

Pssm-ID: 467578 [Multi-domain] Cd Length: 157 Bit Score: 58.40 E-value: 3.34e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 329 VIHPDGTKCLLGR--QKRFPPGMF-TCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPSSLMIGCLAVAV 405
Cdd:cd04697  33 VRNAAGRLLVQKRtmDKDYCPGYLdPATGGVVGAGESYEENARRELEEELGIDGVPLRPLFTFYYEDDRSRVWGALFECV 112

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 21312664 406 ST-EIKVDKNEIEDARWFTREQVVDVltkgKQQAFFVPPSRAIAHQLIK 453
Cdd:cd04697 113 YDgPLKLQPEEVAEVDWMSEDEILQA----ARGEEFTPDGRVALERYLA 157

Ankyrin repeats (3 copies);

Pssm-ID: 463710 [Multi-domain] Cd Length: 91 Bit Score: 55.89 E-value: 5.43e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 21312664    50 LMYAARNGHPDVVQFLLEKGCDRSLVNKARQTALDIAAFWGYRHIANLLAN 100
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLE 51

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

Pssm-ID: 467564 [Multi-domain] Cd Length: 135 Bit Score: 55.27 E-value: 2.51e-09

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 21312664 338 LLGRQKRFP-PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQP 389
Cdd:cd04681  20 LFVRRAKEPgKGKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYLCSLP 72

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

Pssm-ID: 467603 [Multi-domain] Cd Length: 187 Bit Score: 56.38 E-value: 2.61e-09

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21312664 338 LLGRQKRFP-------PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVsCQPWPMP 393
Cdd:cd24155  59 VLIEQFRIGalardesPWLLEIVAGMIDAGETPEDVARREAEEEAGLTLDALEPI-ASYYPSP 120

Ankyrin repeats (3 copies);

Pssm-ID: 463710 [Multi-domain] Cd Length: 91 Bit Score: 53.20 E-value: 5.02e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 21312664    16 LHSSAAEGN--VAKLagILSHSPSllnETSENGWTALMYAARNGHPDVVQFLLEKGCD 71
Cdd:pfam12796  34 LHLAAKNGHleIVKL--LLEHADV---NLKDNGRTALHYAARSGHLEIVKLLLEKGAD 86

bifunctional NMN adenylyltransferase/ADP-ribose pyrophosphatase and similar proteins; Bacterial NadM-Nudix is a bifunctional enzyme containing a nicotinamide mononucleotide (NMN) adenylyltransferase (NMNAT) and an ADP-ribose pyrophosphatase (ADPRase) domain. NMNAT was initially identified as an NAD+ synthase that catalyzes the reversible conversion of NMN to NAD+ in the final step of both the de novo biosynthesis and salvage pathways in most organisms across all three kingdoms of life ADPRase is a member of the NUDIX family proteins, catalyzes the metal-induced and concerted general acid-base hydrolysis of ADP ribose (ADPR) into AMP and ribose-5'-phosphate (R5P). Additional members in this cd include bacterial transcriptional regulator, NrtR, which represses the transcription of NAD biosynthetic genes in vitro and adenosine diphosphate ribose (ADPR), as well as NadQ, a NUDIX-like ATP-responsive regulator of NAD biosynthesis. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belong to this superfamily requires a divalent cation, such as Mg2+ or Mn2+ for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, U=I, L or V) which functions as 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 _ "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: 467585 [Multi-domain] Cd Length: 132 Bit Score: 54.47 E-value: 5.51e-09

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 321 VDPVVImqVIHPDGTKCLLGRQKRFP-------PGmftclaGFIEPGETIEDAVRREVEEESGVKVGHVQ 383
Cdd:cd18873   5 VDCVIF--GFDDGELKVLLIKRKNEPfkggwalPG------GFVREDETLEDAARRELREETGLKDIYLE 66

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: 54.11 E-value: 5.69e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 319 PRVDPVVImqVIHPDGtKCLLGRQK-RFPPGMFtCLA-GFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQpwpmpSSL 396
Cdd:cd04678   1 PRVGVGVI--VLNDDG-KVLLGRRKgSHGAGTW-ALPgGHLEFGESFEECAAREVLEETGLEIRNVRFLTVT-----NDV 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 21312664 397 M---------IGCLAVAVSTEIKV--DKNEIEDARWFTREQV 427
Cdd:cd04678  72 FeeegkhyvtIFVLAEVDDGEPEEnmEPDKCEGWEWFSWDEL 113

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: 54.10 E-value: 5.89e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 357 IEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPSSLMIGC------LAVAVSTEIKVDKN-EIEDARWFTREQVVD 429
Cdd:cd03673  36 LEPGETPEEAAVREVEEETGLRVRLGRPLGTTRYTYTRKGKGILkkvhywLMRALGGEFLPQPEeEIDEVRWLPPDEARR 115


                ...
gi 21312664 430 VLT 432
Cdd:cd03673 116 LLT 118

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

Pssm-ID: 467596 [Multi-domain] Cd Length: 147 Bit Score: 53.78 E-value: 1.32e-08

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 21312664 338 LLGRQKRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQY 384
Cdd:cd18886  15 LLNRNKKPNMGKWNGVGGKLEPGESPEECAIREVFEETGLELEDLQL 61

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

Pssm-ID: 467588 [Multi-domain] Cd Length: 121 Bit Score: 52.97 E-value: 1.39e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 355 GFIEPGETIEDAVRREVEEESG--VKVGH---VQYVSCQPWPMPSSLMI---GCLAVAVSTEIKVDKNEIEDARWFTREQ 426
Cdd:cd18876  30 GVVEAGESPLQAARREVREELGldVPVGRllaVDWVPPAGGGDDAVLFVfdgGVLTPEQAAAIRLQDEELSAYRFVTPEE 109


                ....*.
gi 21312664 427 VVDVLT 432
Cdd:cd18876 110 AAELLP 115

Ankyrin repeats (many copies);

Pssm-ID: 372654 [Multi-domain] Cd Length: 54 Bit Score: 50.35 E-value: 1.97e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 21312664    46 GWTALMYAARNGHPDVVQFLLEKGCDRSLVNKARQTALDIAAFWGYRHIANLL 98
Cdd:pfam13637   1 ELTALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFAASNGNVEVLKLL 53

Ankyrin repeats (many copies);

Pssm-ID: 372654 [Multi-domain] Cd Length: 54 Bit Score: 48.81 E-value: 7.40e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 21312664    16 LHSSAAEGNVAKLAGILSHSPSLlNETSENGWTALMYAARNGHPDVVQFLL 66
Cdd:pfam13637   5 LHAAAASGHLELLRLLLEKGADI-NAVDGNGETALHFAASNGNVEVLKLLL 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: 467590 [Multi-domain] Cd Length: 142 Bit Score: 51.05 E-value: 1.02e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 329 VIHPDGTKCLLGRqkRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKV-----------GHVQYVS---CQpwpmps 394
Cdd:cd18879  24 VVLRDAGRVLLVR--RADNGRWTPVTGIVEPGEQPADAAVREVLEETGVDVeverlasvgasPPVTYPNgdqCQ------ 95

                        90       100
                ....*....|....*....|....*...
gi 21312664 395 SLMIGCLAVAVSTEIKVDKNEIEDARWF 422
Cdd:cd18879  96 YLDLTFRCRPVGGEARVNDDESLEVGWF 123

Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrin- actin cytoskeleton. This repeat-domain is a 'membrane-binding' domain of up to 24 repeated units, and it mediates most of the protein's binding activities. Repeats 13-24 are especially active, with known sites of interaction for the Na/K ATPase, Cl/HCO(3) anion exchanger, voltage-gated sodium channel, clathrin heavy chain and L1 family cell adhesion molecules. The ANK repeats are found to form a contiguous spiral stack such that ion transporters like the anion exchanger associate in a large central cavity formed by the ANK repeat spiral, while clathrin and cell adhesion molecules associate with specific regions outside this cavity.

Pssm-ID: 459634 [Multi-domain] Cd Length: 34 Bit Score: 47.28 E-value: 1.53e-07

                          10        20        30
                  ....*....|....*....|....*....|....
gi 21312664    45 NGWTALMYAA-RNGHPDVVQFLLEKGCDRSLVNK 77
Cdd:pfam00023   1 DGNTPLHLAAgRRGNLEIVKLLLSKGADVNARDK 34

ADP-ribose pyrophosphatase NudF; Provisional

Pssm-ID: 182682 [Multi-domain] Cd Length: 202 Bit Score: 51.27 E-value: 2.38e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664  347 PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQ----YVSCqpwpmP------SSLMIGCLAVAVSTEIKVDKNEI 416
Cdd:PRK10729  81 PWLLEMVAGMIEEGESVEDVARREAIEEAGLIVGRTKpvlsYLAS-----PggtserSSIMVGEVDATTASGIHGLADEN 155

                         90
                 ....*....|..
gi 21312664  417 EDAR--WFTREQ 426
Cdd:PRK10729 156 EDIRvhVVSREQ 167

Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrin- actin cytoskeleton. This repeat-domain is a 'membrane-binding' domain of up to 24 repeated units, and it mediates most of the protein's binding activities.

Pssm-ID: 463933 [Multi-domain] Cd Length: 30 Bit Score: 46.48 E-value: 2.83e-07

                          10        20
                  ....*....|....*....|....*..
gi 21312664    45 NGWTALMYAARNGHPDVVQFLLEKGCD 71
Cdd:pfam13606   1 DGNTPLHLAARNGRLEIVKLLLENGAD 27

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

Pssm-ID: 467549 [Multi-domain] Cd Length: 132 Bit Score: 49.17 E-value: 2.95e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 337 CLLGRQKrfPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQ---------PW-PMPSSLMIGCLAVAVS 406
Cdd:cd04664  17 LLLKRTD--DGGFWQSVTGGIEDGETPWQAALRELKEETGLDPLELQLIDLNvsnfyeifdDWrPGVTVNTEHVFAVEVP 94

                        90       100
                ....*....|....*....|....*.
gi 21312664 407 TEIKVDKN-EIEDARWFTREQVVDVL 431
Cdd:cd04664  95 EEQPIRLSpEHTDYRWLPYEEAAELL 120

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: 49.05 E-value: 3.81e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 354 AGFIEPGETIEDAVRREVEEESGVKVG-------------HVQYvscqpwpmP-----SSLMIGCLAVAVSTEIKVDKNE 415
Cdd:cd04677  41 GGAMELGESLEETARREVFEETGLTVEelellgvysgkdlYYTY--------PngdevYNVTAVYLVRDVSGELKVDDEE 112


                ....*..
gi 21312664 416 IEDARWF 422
Cdd:cd04677 113 SLELRFF 119

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

Pssm-ID: 467605 Cd Length: 146 Bit Score: 48.33 E-value: 9.08e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 318 YPRVDPVVIMqVIHPDGTKCLLGRQKRFP------PGMFT--ClAGFIEpGETIEDAVRREVEEESGVKVGHVQYVScQP 389
Cdd:cd24157   1 YDRGDAAAVL-LYDPKRKTVVLVRQFRAPaylgggDGWLIeaC-AGLLD-GDDPEDCIRREAEEETGYRLGDLEKVF-TA 76


                ....*...
gi 21312664 390 WPMPSSLM 397
Cdd:cd24157  77 YSSPGIVT 84

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: 47.89 E-value: 9.61e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 329 VIHPDgtKCLLGRQKRfPP--GMFTCLAGFIEPGETIEDAVRREVEEESGVK------VGHVQYVSCQPWPMPSS--LMI 398
Cdd:cd04673   8 VFRDG--RVLLVRRGN-PPdaGLWSFPGGKVELGETLEDAALRELREETGLEaevvglLTVVDVIERDEAGRVRFhyVIL 84

                        90       100
                ....*....|....*....|....*....
gi 21312664 399 GCLAVAVSTEIKVDkNEIEDARWFTREQV 427
Cdd:cd04673  85 DFLAEWVSGEPVAG-DDALDARWFSLEEL 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: 47.24 E-value: 1.17e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21312664 355 GFIEPGETIEDAVRREVEEESGVKVGHVQYV---SCQPWPMPSSLMIgCLAVAVSTEIKVDKNEIEDARWFTR 424
Cdd:cd04665  29 GKREPGETIEEAARRELYEETGAVIFELKPLgqySVHGKGQEFFGAV-YYAEVKSFEPILPYFETAEVRLFDE 100

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: 47.56 E-value: 1.62e-06

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 21312664 329 VIHPDGtKCLLGRQKRFPpGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQP 389
Cdd:cd03671  10 LFNRDG-QVLVGRRIDVP-GAWQFPQGGIDEGEDPEEAALRELYEETGLSPEDVEIIAETP 68

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.

Pssm-ID: 197603 [Multi-domain] Cd Length: 30 Bit Score: 44.12 E-value: 1.83e-06

                           10        20
                   ....*....|....*....|....*..
gi 21312664     45 NGWTALMYAARNGHPDVVQFLLEKGCD 71
Cdd:smart00248   1 DGRTPLHLAAENGNLEVVKLLLDKGAD 27

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

Pssm-ID: 467543 [Multi-domain] Cd Length: 138 Bit Score: 47.13 E-value: 2.01e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 354 AGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPSS------LMIGCLAVAVSTEIKVDKnEIEDARWFTREQV 427
Cdd:cd03675  30 AGHLEPGESLLEAAIRETLEETGWEVEPTALLGIYQWTAPDNgvtylrFAFAGELLEHLPDQPLDS-GIIRAHWLTLEEI 108


                ..
gi 21312664 428 VD 429
Cdd:cd03675 109 LA 110

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

Pssm-ID: 467598 [Multi-domain] Cd Length: 149 Bit Score: 47.48 E-value: 2.04e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 21312664 321 VDPVVIMQVIH-PDGTKCL-LGRQKRFPPGMFtCL---AGFIEPGETIEDAVRREVEEESGVKVGHVQYVS 386
Cdd:cd18888   2 VDAVAIIAILKrKLKPPELvLVKQYRPPVNAY-TIefpAGLVDPGESPEQAALRELKEETGYTGEKVLSVS 71

Ankyrin repeat [Signal transduction mechanisms];

Pssm-ID: 440430 [Multi-domain] Cd Length: 289 Bit Score: 49.18 E-value: 2.22e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664  16 LHSSAAEGN--VAKLagILSHSPSLlNETSENGWTALMYAARNGHPDVVQFLLEKGCDRSLVNKARQTALDIAAFWGYRH 93
Cdd:COG0666 190 LHLAAENGHleIVKL--LLEAGADV-NAKDNDGKTALDLAAENGNLEIVKLLLEAGADLNAKDKDGLTALLLAAAAGAAL 266

                        90
                ....*....|...
gi 21312664  94 IANLLANAKGGKK 106
Cdd:COG0666 267 IVKLLLLALLLLA 279

NADH pyrophosphatase-like rudimentary NUDIX domain; The N-terminal domain in NADH pyrophosphatase, which has a rudiment Nudix fold according to SCOP.

Pssm-ID: 462747 Cd Length: 96 Bit Score: 45.81 E-value: 2.23e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664   148 TVYLLFSDLNPLVtlggnkESSQQPEVRLCQLNYPDVkgylaQPEKITLVFLGVElemrKGSPAQAGGVPEEEEDGLvaw 227
Cdd:pfam09296   2 ARWLLFWGGRLLL------KKEGDNRLLLPAGELPEL-----VLDLTEPVFLGLD----EGAPVFAVDVSAAAELAL--- 63

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 21312664   228 falgIEPGAAEEFKQrhencyflhppmpALLQLKEKEAGVVAQARSVLAW 277
Cdd:pfam09296  64 ----PEGGEFADLRA-------------LMLALDAEDAGLAAQARALLYW 96

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

Pssm-ID: 467548 [Multi-domain] Cd Length: 132 Bit Score: 46.52 E-value: 3.01e-06

                        10        20
                ....*....|....*....|....*....
gi 21312664 354 AGFIEPGETIEDAVRREVEEESGVKVGHV 382
Cdd:cd04663  32 KGTVEPGESPEEAALRELAEETGLTGARV 60

ankyrin repeat protein; Provisional

Pssm-ID: 222984 [Multi-domain] Cd Length: 422 Bit Score: 49.28 E-value: 3.08e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664   39 LNETSENGWTALMYAARNGHPDVVQFLLEKGCDRSLVNKARQTALDIAAFWGYRHIANLLANAKGGkkpwflTNEVDECE 118
Cdd:PHA03100 185 INIKDVYGFTPLHYAVYNNNPEFVKYLLDLGANPNLVNKYGDTPLHIAILNNNKEIFKLLLNNGPS------IKTIIETL 258


                 ....*....
gi 21312664  119 NYFSRTLLD 127
Cdd:PHA03100 259 LYFKDKDLN 267

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: 45.52 E-value: 4.46e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 329 VIHpDGTKCLLGRqkRfPPGMFtcLAGF-------IEPGETIEDAVRREVEEESGVKVGHVQYVSC--QPWPMPSSLMIG 399
Cdd:cd03425   7 IIV-DDGRVLIAQ--R-PEGKH--LAGLwefpggkVEPGETPEQALVRELREELGIEVEVGEPLGTveHDYPDFHVRLHV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 21312664 400 CLAVAVSTEIKvdKNEIEDARWFTREQVVDVLtkgkqqafFVPPSRAIAHQLI 452
Cdd:cd03425  81 YLCTLWSGEPQ--LLEHQELRWVTPEELDDLD--------WLPADIPIVEALL 123

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

Pssm-ID: 467574 [Multi-domain] Cd Length: 142 Bit Score: 45.63 E-value: 6.40e-06

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 21312664 328 QVIH-----PDGTKCLLgrQKRFP-----PGMF--TClAGFIEPGETIEDAVRREVEEESGVKV 379
Cdd:cd04692  27 RTVHvwlvnPEEGRLLL--QKRSAnkddfPGLWdiSA-AGHIDAGETYEEAAVRELEEELGLTV 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.

Pssm-ID: 467586 [Multi-domain] Cd Length: 125 Bit Score: 45.35 E-value: 6.60e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 323 PVVIMQVIHPDGtKCLLGRQKRFPpGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPSS------- 395
Cdd:cd18874   3 PTVGALIFNPDG-KVLLVRSHKWN-DLYGIPGGKVEWGETLEEALKREVKEETGLDITDIRFILVQESINSEEfhkpahf 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 21312664 396 LMIGCLAVAVSTEIkVDKNEIEDARWFTREQVVD 429
Cdd:cd18874  81 VFVDYLARTDSSEV-VLNEEAVEYLWVEPEEALK 113

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: 44.83 E-value: 8.50e-06

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21312664 345 FPPGmftclaGFIEPGETIEDAVRREVEEESG--VKVGHVQYV 385
Cdd:cd18880  28 ILPG------GGQEHGETLPEALKRECLEETGldVEVGDLLFV 64

NADH pyrophosphatase zinc ribbon domain; This domain is found in between two duplicated NUDIX domains. It has a zinc ribbon structure.

Pssm-ID: 430510 [Multi-domain] Cd Length: 32 Bit Score: 42.20 E-value: 9.86e-06

                          10        20
                  ....*....|....*....|....
gi 21312664   279 SRYKFCPTCGSATKIEEGGYKRVC 302
Cdd:pfam09297   1 RTHRFCGRCGAPTVPAEGGWARVC 24

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

Pssm-ID: 467602 [Multi-domain] Cd Length: 121 Bit Score: 44.13 E-value: 1.37e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 341 RQKRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYV---SCQPWPMPSSLMIGCLAVAVSTEIKVDKNEIE 417
Cdd:cd24154  24 DKRIFPLALDMSVGGHVSSGETYEQAFVRELQEELNLDLDQLSYRvlgKLTPYEHGVSAFMKVYEIRSDETPDYNPDDFS 103

                        90
                ....*....|....*..
gi 21312664 418 DARWFTREQVVDVLTKG 434
Cdd:cd24154 104 EAFWLTPEELLKRIAAG 120

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

Pssm-ID: 467569 [Multi-domain] Cd Length: 130 Bit Score: 44.20 E-value: 1.71e-05

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21312664 336 KCLLGRQKRFP-PGMFTCLAGFIEPGETIEDAVRREVEEESGVKV 379
Cdd:cd04686  13 KLLLIRKTRGPyQGRYDLPGGSQEFGESLEDALKREFAEETGMTV 57

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

Pssm-ID: 467544 Cd Length: 153 Bit Score: 44.41 E-value: 2.08e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 312 GVHntsyprvdpvVIMQVIHPDGTKCLLGR---QKRFPPGMFTCL-AGFIEPGETIEDAVRREVEEESGV---------- 377
Cdd:cd03676   8 GVH----------LNGYVRDGDGLRLWVARrsaTKATYPGKLDNLvAGGVPAGESPLETLVREAEEEAGLpedlarqarp 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 378 KVGHVQYVSCQP--WPMPSSLMIGCLAVAVSTEIKVDKNEIEDARWFTREQVVDVLTKGK 435
Cdd:cd03676  78 AAGRVSYFYRSDegGLQPEVLYVYDLELPEDFVPKPQDGEVESFELMSVDEVLEALRAGE 137

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

Pssm-ID: 467555 [Multi-domain] Cd Length: 130 Bit Score: 43.84 E-value: 2.63e-05

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 21312664 325 VIMQVIHPDGTKCLLGRQ-KRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVK 378
Cdd:cd04671   2 VVAAVIINEQGEVLMIQEaKRSCRGKWYLPAGRVEPGESIVEAAKREVKEETGLK 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: 43.71 E-value: 3.13e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 21312664 338 LLGRQKRF-----PPGmftclaGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPS 394
Cdd:cd18875  18 VLDRVKKDwggytFPG------GHVEPGESFVDSVIREVKEETGLTIKNPELCGIKQWINPD 73

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: 43.05 E-value: 4.37e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 346 PPGmftclaGFIEPGETIEDAVRREVEEESGVKVGHVQ-------YVSCQP----WPMPSSLMIgCLAVAV--------S 406
Cdd:cd04694  34 PPG------GHVELGESLLEAGLRELQEETGLEVSDIQslsllglWESVYPtllsIGLPKRHHI-VVYYLVklseshenQ 106

                        90       100
                ....*....|....*....|....*.
gi 21312664 407 TEIKVDKNEIEDARWFTREQVVDVLT 432
Cdd:cd04694 107 EQLKLQEDEVDAAVWLPKSLLAKLLE 132

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: 42.52 E-value: 5.34e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 329 VIHPDGtKCLL----GRQKRFPPGmftclaGFIEPGETIEDAVRREVEEESGVKVGhvqyvscqpwpmPSSL-------- 396
Cdd:cd04690   7 IIIKDG-RLLLvrkrGTDAFYLPG------GKREPGETPLQALVRELKEELGLDLD------------PDSLrflgtfea 67

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 21312664 397 -----------MIgCLAVAVSTEIKVDkNEIEDARWFTREQVVDVL 431
Cdd:cd04690  68 paanepgttvrMT-CFTADYDGEPQPA-AEIEELRWLDPADPDDDR 111

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

Pssm-ID: 467566 [Multi-domain] Cd Length: 137 Bit Score: 42.98 E-value: 5.40e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21312664 321 VDPVVIMQvihpDGTKCLLGRqkRFPPGM----FTCLAGFIEPGETIEDAVRREVEEESGVKV 379
Cdd:cd04683   1 VDVHLLLV----RGDEVLLLR--RANTGYddgwWHLPAGHVEAGETVRAAAVREAKEELGVEI 57

nucleoside triphosphatase NudI; Provisional

Pssm-ID: 185369 [Multi-domain] Cd Length: 141 Bit Score: 42.43 E-value: 8.65e-05

                         10        20        30
                 ....*....|....*....|....*....|
gi 21312664  347 PGMFTCLAGFIEPGETIEDAVRREVEEESG 376
Cdd:PRK15472  30 PGQWALSGGGVEPGERIEEALRREIREELG 59

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

Pssm-ID: 467563 [Multi-domain] Cd Length: 121 Bit Score: 41.85 E-value: 9.25e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 355 GFIEPGETIEDAVRREVEEESGVKVG------------------HVQYVSCQPWpmpsslmigclavaVSTEIKVDKNEI 416
Cdd:cd04680  30 GGVDKGETAEEAARRELREEAGVVLTgpprlfgvyfnrrvsprdHVALYRVREF--------------EQTEPPEPNGEI 95


                ....*.
gi 21312664 417 EDARWF 422
Cdd:cd04680  96 AEAGFF 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: 467570 [Multi-domain] Cd Length: 130 Bit Score: 42.15 E-value: 1.04e-04

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21312664 345 FPPGmftclaGFIEPGETIEDAVRREVEEESGVKVGHVQYVSC 387
Cdd:cd04688  27 RLPG------GRVEFGETSEDALVREFKEELGVEVEVVRLLFV 63

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

Pssm-ID: 467579 [Multi-domain] Cd Length: 118 Bit Score: 41.45 E-value: 1.13e-04

                        10        20        30
                ....*....|....*....|....*....|...
gi 21312664 355 GFIEPGETIEDAVRREVEEESG--VKVGHVQYV 385
Cdd:cd04699  33 GRLEPGESPEEALKREVKEETGldVSVGELLDT 65

nucleoside diphosphate-linked moiety X)) motif 16; U8 SnoRNA-decapping enzyme, also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 16/Nudt16, is encoded by the human NUDT16 gene and a RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. 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: 467581 Cd Length: 175 Bit Score: 42.73 E-value: 1.31e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 21312664 324 VVIMQVIHpDGtkcLLGrqkrFPpgmftclAGFIEPGETIEDAVRREVEEESG-----VKVGHVQYVSCQP 389
Cdd:cd18869  27 TLLMQMRF-DG---LLG----FP-------GGFVDTGESLEEGLNRELREELGlahavFPVTEDDYRSSHV 82

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: 40.75 E-value: 2.37e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 319 PRVD-PVVIMQvihpDGtKCLLGRQKRFP-------PGmftclaGFIEPGETIEDAVRREVEEESGVKVG---------H 381
Cdd:cd04679   1 PRVGcGAAILD----DG-RLLLVLRLRAPeaghwglPG------GKVDWLETVEDAVRREILEELGLEIEltrllcvvdQ 69

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 21312664 382 VQYVSCQPWPMPSSlmigcLAVAVSTEIKVDKNE-IEDARWFTREQVVDVLTKGKQQA 438
Cdd:cd04679  70 IDAADGEHWVAPVY-----LAEIFSGEPRLMEPEkHGGIGWFALDALPQPLTVATRDA 122

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

Pssm-ID: 467608 [Multi-domain] Cd Length: 151 Bit Score: 41.34 E-value: 2.38e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 21312664 336 KCLLGRQKRFPPGMFT--CLAGFIEPGETIEDAVRREVEEESGVKvGHVQYVS 386
Cdd:cd24160  33 RMLFVRQMRPAVGAATleIPAGLIDPGETPEEAARRELAEETGLS-GDLTYLT 84

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: 40.35 E-value: 3.39e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 340 GRQKRF-PPGmftclaGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPwpMPSSLMIGCLAVAVSTEIKVDKNEIED 418
Cdd:cd04667  18 RRGGRWlLPG------GKIEPGESPLEAAIRELKEETGLAALSLLYLFEHE--GPHKLHHVFLAEAPDGGRPRPGNEIAR 89

                        90
                ....*....|....*
gi 21312664 419 ARWFTREQVVDVLTK 433
Cdd:cd04667  90 CRWVSADQLRDLNLS 104

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: 40.66 E-value: 3.57e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 348 GMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQPWPMPSSLMIgcLAVAVSTEIKVDK-------NEIEDAR 420
Cdd:cd04700  43 GLWHIPSGAVEDGENPQDAAVREACEETGLRVRLVKFLGAYLGRFPDGVLV--LRHVWLAEPEPGQvlapaftDEIAEAS 120

                        90
                ....*....|....*
gi 21312664 421 WFTREQVVDVLTKGK 435
Cdd:cd04700 121 FVSREEFAQLYAAGQ 135

NUDIX hydrolase subfamily; Nucleoside triphosphatase NudI catalyzes the hydrolysis of nucleoside triphosphates, with a preference for pyrimidine deoxynucleoside triphosphates (dUTP, dTTP and dCTP). It is a members of the NUDIX hydrolase superfamily which 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: 467577 [Multi-domain] Cd Length: 134 Bit Score: 40.30 E-value: 3.79e-04

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 21312664 347 PGMFTCLAGFIEPGETIEDAVRREVEEESGVK--VGHVqyvscQPW 390
Cdd:cd04696  28 PGQWALSGGGVEPGERIEEALRREIREELGEQliLSDI-----TPW 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: 467559 [Multi-domain] Cd Length: 144 Bit Score: 40.47 E-value: 3.91e-04

                        10        20
                ....*....|....*....|....*.
gi 21312664 354 AGFIEPGETIEDAVRREVEEESGVKV 379
Cdd:cd04676  46 AGAIEPGEHPAEAVIREVREETGLLV 71

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

Pssm-ID: 129162 [Multi-domain] Cd Length: 185 Bit Score: 40.96 E-value: 5.58e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664   344 RFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVScQPWPMP------SSLMIGCL--AVAVSTEIKVDKNE 415
Cdd:TIGR00052  73 GEEPWLLELSAGMVEKGESPEDVARREAIEEAGYQVKNLRKLL-SFYMSPggvtelIHLFIAEVddNQAAGIGGGADEEE 151


                  ..
gi 21312664   416 IE 417
Cdd:TIGR00052 152 IE 153

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional

Pssm-ID: 140343 [Multi-domain] Cd Length: 664 Bit Score: 42.19 E-value: 5.73e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664   15 ELHSSAAEGNVAKlAGILSHSPSLLNETSENGWTALMYAARNGHPDVVQFLLEKGCDRSLVNKARQTALDIAAFWGYRHI 94
Cdd:PTZ00322  85 ELCQLAASGDAVG-ARILLTGGADPNCRDYDGRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREV 163


                 ....
gi 21312664   95 ANLL 98
Cdd:PTZ00322 164 VQLL 167

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

Pssm-ID: 467609 [Multi-domain] Cd Length: 137 Bit Score: 39.85 E-value: 6.02e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 21312664 330 IHPDGTKCLLgRQKRFPPGMfTCL---AGFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQpWPMPS 394
Cdd:cd24161  11 ITDDGEVVLV-EQYRYPLGG-WSWeipAGGWPEGEDPEEAARRELREETGLRAERWTPLGRF-YPSNG 75

RNA pyrophosphohydrolase; Reviewed

Pssm-ID: 234820 [Multi-domain] Cd Length: 156 Bit Score: 40.14 E-value: 6.32e-04

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 21312664  355 GFIEPGETIEDAVRREVEEESGVKVGHVQYVSCQP-W 390
Cdd:PRK00714  39 GGIDPGETPEQAMYRELYEEVGLRPEDVEILAETRdW 75

dihydroneopterin triphosphate pyrophosphatase; Provisional

Pssm-ID: 236516 [Multi-domain] Cd Length: 148 Bit Score: 39.88 E-value: 7.34e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 21312664  323 PVVIMQVIHPDGTKCLLgRQKRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQY--VSCQ 388
Cdd:PRK09438   7 PVSVLVVIYTPDLGVLM-LQRADDPDFWQSVTGSLEEGETPAQTAIREVKEETGIDVLAEQLtlIDCQ 73

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

Pssm-ID: 467545 [Multi-domain] Cd Length: 123 Bit Score: 39.48 E-value: 7.66e-04

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21312664 336 KCLLGRQKRFP-PGMFTCLAGFIEPGETIEDAVRREVEEESGVKV 379
Cdd:cd04511  14 KVLLCRRAIEPrKGYWTLPAGFMELGETTEQGAARETREEAGARV 58

isopentenyl-diphosphate Delta-isomerase;

Pssm-ID: 235156 [Multi-domain] Cd Length: 184 Bit Score: 40.34 E-value: 7.92e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664  329 VIHPDGtKCLLGRQ---KRFPPGMFT---ClaGFIEPGETIEDAVRREVEEESGVKV-------GHVQYVScqpwPMPSS 395
Cdd:PRK03759  41 LFDADG-RLLVTRRalsKKTWPGVWTnscC--GHPQPGESLEDAVIRRCREELGVEItdlelvlPDFRYRA----TDPNG 113

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 21312664  396 L----MIGCLAVAVSTEIKVDKNEIEDARWFTREQVVDVLTKG 434
Cdd:PRK03759 114 IveneVCPVFAARVTSALQPNPDEVMDYQWVDPADLLRAVDAT 156

NUDIX hydrolase YfcD; Provisional

Pssm-ID: 185291 [Multi-domain] Cd Length: 180 Bit Score: 39.78 E-value: 1.16e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664  329 VIHPDGTKCLLGRQ---KRFPPGMF-TCLAGFIEPGETIEDAVRREVEEESGVK----VGHVQYV----SCQPWpmpssl 396
Cdd:PRK15393  43 VVHDGMGKILVQRRtetKDFLPGMLdATAGGVVQAGEQLLESARREAEEELGIAgvpfAEHGQFYfedeNCRVW------ 116

                         90       100       110
                 ....*....|....*....|....*....|..
gi 21312664  397 miGCLAVAVST-EIKVDKNEIEDARWFTREQV 427
Cdd:PRK15393 117 --GALFSCVSHgPFALQEEEVSEVCWMTPEEI 146

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 40.38 E-value: 1.74e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21312664  321 VDPVVIMQvihpdgTKCLLGRQKRFP-------PGmftclaGFIEPGETIEDAVRREVEEESGVKV 379
Cdd:PRK05379 206 VDAVVVQS------GHVLLVRRRAEPgkglwalPG------GFLEQDETLLDACLRELREETGLKL 259

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: 38.30 E-value: 2.29e-03

                        10        20
                ....*....|....*....|....*
gi 21312664 355 GFIEPGETIEDAVRREVEEESGVKV 379
Cdd:cd03428  35 GHVEPGESELETALRETKEETGLTV 59

mutator mutT protein; All proteins in this family for which functions are known are involved in repairing oxidative damage to dGTP (they are 8-oxo-dGTPases). This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). Lowering the threshold picks up members of MutT superfamily well. [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 200031 [Multi-domain] Cd Length: 128 Bit Score: 37.55 E-value: 3.31e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 21312664   342 QKRFPPGmftclaGFIEPGETIEDAVRREVEEESGVKVGH 381
Cdd:TIGR00586  31 KLLEFPG------GKEEGGETPEQAVVRELEEEIGIPQHF 64

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

Pssm-ID: 467568 [Multi-domain] Cd Length: 138 Bit Score: 37.55 E-value: 3.44e-03

                        10        20        30
                ....*....|....*....|....*....|....*
gi 21312664 345 FPPGmftclaGFIEPGETIEDAVRREVEEESGVKV 379
Cdd:cd04685  31 FTPG------GGVEPGESPEQAAVRELREETGLRL 59

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 39.09 E-value: 3.73e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 21312664  327 MQVIH--------PDGtKCLLGR--QKRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHvqyvsCQPW 390
Cdd:PRK08999   2 MKRIHvaagvirdADG-RILLARrpEGKHQGGLWEFPGGKVEPGETVEQALARELQEELGIEVTA-----ARPL 69

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: 467571 Cd Length: 145 Bit Score: 37.46 E-value: 4.57e-03

                        10        20
                ....*....|....*....|....*
gi 21312664 355 GFIEPGETIEDAVRREVEEESGVKV 379
Cdd:cd04689  37 GGVEENENLEEAIRRELKEELGVEV 61

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: 37.75 E-value: 4.73e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 286 TCGSATKIEEGGYKRVcVRETCPSLQGVHNT-SYPRVDPVVIMQVIHPDGTkCLLGRQKRFPPG-MFTCL-AGFIEPGET 362
Cdd:cd24159   5 KTLSSRVVYKGGFLKV-HRDQVRLPDGSTSTrEYITHPGAVAVVPLLDDGR-VVMERQYRYPLKrVFLEFpAGKIDPGED 82

                        90
                ....*....|....*.
gi 21312664 363 IEDAVRREVEEESGVK 378
Cdd:cd24159  83 TLETAKRELLEETGYE 98

nudix hydrolase

Pssm-ID: 215184 [Multi-domain] Cd Length: 144 Bit Score: 37.15 E-value: 5.57e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 21312664  319 PRVDPVVIMQvihpDGTKCLLGRQKR-FPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVS 386
Cdd:PLN02325   8 PRVAVVVFLL----KGNSVLLGRRRSsIGDSTFALPGGHLEFGESFEECAAREVKEETGLEIEKIELLT 72

Isopentenyl diphosphate isomerase; Isopentenyl diphosphate (IPP) isomerase, a member of the NUDIX hydrolase superfamily, is a key enzyme in the isoprenoid biosynthetic pathway. Isoprenoids comprise a large family of natural products including sterols, carotenoids, dolichols and prenylated proteins. These compounds are synthesized from two precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). IPP isomerase catalyzes the interconversion of IPP and DMAPP by a stereoselective antarafacial transposition of hydrogen. The enzyme requires one Mn2+ or Mg2+ ion in its active site to fold into an active conformation and also contains 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. The metal binding site is present within the active site and plays structural and catalytical roles. IPP isomerase is well represented in several bacteria, archaebacteria and eukaryotes, including fungi, mammals and plants. Despite sequence variations (mainly at the N-terminus), the core structure is highly conserved.

Pssm-ID: 467529 [Multi-domain] Cd Length: 162 Bit Score: 37.47 E-value: 6.43e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21312664 359 PGETIEDAVRREVEEESGVK------VGHVQYVScqpwPMPSSL----MIGCLAVAVSTEIKVDKNEIEDARWFTREQVV 428
Cdd:cd02885  68 PGEGVEDAAQRRLREELGIPvcdleeLPRFRYRA----TDDNGLveheIDHVFVGRADGDPVPNPEEVSDYRWVSLEELR 143


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gi 21312664 429 D 429
Cdd:cd02885 144 E 144