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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 118 VPVRGAIMLNQDMDEVVLVKGWKKGANWSFPRGKINKGEKDLDCAIREVYEETGFDVRqaGLVKDDEnvkFIEITMREQH 197
Cdd:cd03672    1 VPVRGAILLNEDLDKVLLVKGWKSNSSWGFPKGKINKDESDADCAIREVYEETGFDIS--DLINDKD---YIELTINGQR 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 121713842 198 MRLYVFRGVPQDTHFEPRTRKEISKIEWYKLSELPTLMKKNKpndeslavANANKFYMVAPFMHPLKKWIAQQKR 272
Cdd:cd03672   76 VRLYIIPGVPEDTPFEPQTRKEISKIEWFDIDDLPKNKKKKG--------KNSNKFYMVNPFVKPLKKWIKKRKQ 142

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  371 PTPQAPAIDRATHPNAVSGIH----PPTHQPESLLAPN--FFPGFPQQFNQADQPENLPRIPRKPYHGTAPPSLPMSTHP 444
Cdd:PHA03247 2622 HAPDPPPPSPSPAANEPDPHPpptvPPPERPRDDPAPGrvSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSLTSLADP 2701

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  445 YA---SNEPSPPFGYHGLPQFQNRHGPEIHALSQTHRPAPAPAPYQQTGDPQFSQPAHAPQIQGATVP-----PASNlPP 516
Cdd:PHA03247 2702 PPpppTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPappaaPAAG-PP 2780

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  517 PKLTSHSLALLNVFKDNSTRSPQPSNPSLVQRSEQTIMAKPKTlhhqdqllgllkGAPPSAPAElSAQPVSPagkrilqr 596
Cdd:PHA03247 2781 RRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAAS------------PAGPLPPPT-SAQPTAP-------- 2839

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  597 SRAEPSTPKRSASHMSTMPKGDPRTSATASGAASGAPNVTHPepnfrgPVKKMQngsnRKNKDRQTQPLASPITILSRPq 676
Cdd:PHA03247 2840 PPPPGPPPPSLPLGGSVAPGGDVRRRPPSRSPAAKPAAPARP------PVRRLA----RPAVSRSTESFALPPDQPERP- 2908

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|...
gi 121713842  677 sgRKESSPTPVisrSPKPPSRASSQPRTNKPKAAEPSKPFQPQ 719
Cdd:PHA03247 2909 --PQPQAPPPP---QPQPQPPPPPQPQPPPPPPPRPQPPLAPT 2946

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 118 VPVRGAIMLNQDMDEVVLVKGWKKGANWSFPRGKINKGEKDLDCAIREVYEETGFDVRqaGLVKDDEnvkFIEITMREQH 197
Cdd:cd03672    1 VPVRGAILLNEDLDKVLLVKGWKSNSSWGFPKGKINKDESDADCAIREVYEETGFDIS--DLINDKD---YIELTINGQR 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 121713842 198 MRLYVFRGVPQDTHFEPRTRKEISKIEWYKLSELPTLMKKNKpndeslavANANKFYMVAPFMHPLKKWIAQQKR 272
Cdd:cd03672   76 VRLYIIPGVPEDTPFEPQTRKEISKIEWFDIDDLPKNKKKKG--------KNSNKFYMVNPFVKPLKKWIKKRKQ 142

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  116 TRVPVRGAIMLNQDmDEVVLVKGWKKGAN--WSFPRGKINKGEKDLDCAIREVYEETGFDVRQAGLVKDDENVKFIEITM 193
Cdd:pfam00293   1 KRRVAVGVVLLNEK-GRVLLVRRSKKPFPgwWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRF 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 121713842  194 REQHMRLYVFRGVPQDThFEPRTRKEISKIEWYKLSELPtLMKKNKPNDESLA 246
Cdd:pfam00293  80 PDEHEILYVFLAEVEGE-LEPDPDGEVEEVRWVPLEELL-LLKLAPGDRKLLP 130

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  371 PTPQAPAIDRATHPNAVSGIH----PPTHQPESLLAPN--FFPGFPQQFNQADQPENLPRIPRKPYHGTAPPSLPMSTHP 444
Cdd:PHA03247 2622 HAPDPPPPSPSPAANEPDPHPpptvPPPERPRDDPAPGrvSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSLTSLADP 2701

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  445 YA---SNEPSPPFGYHGLPQFQNRHGPEIHALSQTHRPAPAPAPYQQTGDPQFSQPAHAPQIQGATVP-----PASNlPP 516
Cdd:PHA03247 2702 PPpppTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPappaaPAAG-PP 2780

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  517 PKLTSHSLALLNVFKDNSTRSPQPSNPSLVQRSEQTIMAKPKTlhhqdqllgllkGAPPSAPAElSAQPVSPagkrilqr 596
Cdd:PHA03247 2781 RRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAAS------------PAGPLPPPT-SAQPTAP-------- 2839

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  597 SRAEPSTPKRSASHMSTMPKGDPRTSATASGAASGAPNVTHPepnfrgPVKKMQngsnRKNKDRQTQPLASPITILSRPq 676
Cdd:PHA03247 2840 PPPPGPPPPSLPLGGSVAPGGDVRRRPPSRSPAAKPAAPARP------PVRRLA----RPAVSRSTESFALPPDQPERP- 2908

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|...
gi 121713842  677 sgRKESSPTPVisrSPKPPSRASSQPRTNKPKAAEPSKPFQPQ 719
Cdd:PHA03247 2909 --PQPQAPPPP---QPQPQPPPPPQPQPPPPPPPRPQPPLAPT 2946

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  415 QADQPENLPRIPRKPYHGTAPPSLPMSTHPYASNEPSPPFGYhgLPQFQNRHGPEIHALSQTHRPAPAPAPYQQTGDPQF 494
Cdd:pfam03154 175 QAQSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQ--PPNQTQSTAAPHTLIQQTPTLHPQRLPSPHPPLQPM 252

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  495 SQPAHAPQIQGATVPPASNLPPPKLTSHSLAllnvfkdnstrspqpSNPSLVQRSEQTIMAKPKTLHHQDQLLGLLKGAP 574
Cdd:pfam03154 253 TQPPPPSQVSPQPLPQPSLHGQMPPMPHSLQ---------------TGPSHMQHPVPPQPFPLTPQSSQSQVPPGPSPAA 317

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  575 PSAPAELSAQPVSPAGKRILQRSRAEPSTPKRSASHMSTMPKGDPRTSATASGAASGAPNVTHPEP-----NFRGP--VK 647
Cdd:pfam03154 318 PGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSMPHIKPPPTTPIPQLPNPQSHKHPPHLSGPSPfqmnsNLPPPpaLK 397

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  648 KMQNGSNRKnkdrqtQPLASPITILSRPQSGRKESSPT--PVISRSPKPPSRASSQPRTNKPKAAEPSKPFQPQILRRSD 725
Cdd:pfam03154 398 PLSSLSTHH------PPSAHPPPLQLMPQSQQLPPPPAqpPVLTQSQSLPPPAASHPPTSGLHQVPSQSPFPQHPFVPGG 471

                         330       340       350
                  ....*....|....*....|....*....|....*..
gi 121713842  726 NLS-LDNILPTRSKDNDGPSQQTAGPPPNDGQGTKPA 761
Cdd:pfam03154 472 PPPiTPPSGPPTSTSSAMPGIQPPSSASVSSSGPVPA 508

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 118 VPVRGAIMLNQDMDEVVLVKGWKKGANWSFPRGKINKGEKDLDCAIREVYEETGFDVRqaGLVKDDEnvkFIEITMREQH 197
Cdd:cd03672    1 VPVRGAILLNEDLDKVLLVKGWKSNSSWGFPKGKINKDESDADCAIREVYEETGFDIS--DLINDKD---YIELTINGQR 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 121713842 198 MRLYVFRGVPQDTHFEPRTRKEISKIEWYKLSELPTLMKKNKpndeslavANANKFYMVAPFMHPLKKWIAQQKR 272
Cdd:cd03672   76 VRLYIIPGVPEDTPFEPQTRKEISKIEWFDIDDLPKNKKKKG--------KNSNKFYMVNPFVKPLKKWIKKRKQ 142

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  116 TRVPVRGAIMLNQDmDEVVLVKGWKKGAN--WSFPRGKINKGEKDLDCAIREVYEETGFDVRQAGLVKDDENVKFIEITM 193
Cdd:pfam00293   1 KRRVAVGVVLLNEK-GRVLLVRRSKKPFPgwWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLHYLAPFDGRF 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 121713842  194 REQHMRLYVFRGVPQDThFEPRTRKEISKIEWYKLSELPtLMKKNKPNDESLA 246
Cdd:pfam00293  80 PDEHEILYVFLAEVEGE-LEPDPDGEVEEVRWVPLEELL-LLKLAPGDRKLLP 130

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 122 GAIMLNQDmDEVVLVK-GWKKGAN-WSFPRGKINKGEKDLDCAIREVYEETGFDVRQAGLVKDDENvkfiEITMREQHMR 199
Cdd:cd02883    4 GAVVFDDE-GRVLLVRrSDGPGPGgWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEF----PDPDEGRHVV 78

                         90       100
                 ....*....|....*....|....*.
gi 121713842 200 LYVFRGVPQDTHFEPRTRKEISKIEW 225
Cdd:cd02883   79 VLVFLARVVGGEPPPLDDEEISEVRW 104

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 122 GAIMLNQDMD--EVVLVKGwKKGANWSFPRGKINKGEKDLDCAIREVYEETGFDVRQaglvkddenVKFI-----EITMR 194
Cdd:cd03673    5 GGVVWRGRGGggEVLLIHR-PRYDDWSLPKGKLEPGETPEEAAVREVEEETGLRVRL---------GRPLgttryTYTRK 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 121713842 195 EQHM--RLYVFRGVPQDTHFEPRTRKEISKIEWYKLSELPTLMK 236
Cdd:cd03673   75 GKGIlkKVHYWLMRALGGEFLPQPEEEIDEVRWLPPDEARRLLT 118

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 122 GAIMLNqDMDEVVLVKGWKKGAN-WSFPRGKINKGEKDLDCAIREVYEETGFDVRqaglvkddenvkFIEI-TMREQH-M 198
Cdd:cd04670    6 GGLVIN-ENNEVLVVQEKYGGPGgWKLPGGLVDPGEDIGEAAVREVFEETGIDTE------------FVSIlGFRHQHpG 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 121713842 199 R-----LY-VFRGVP---QDTHFEPRtrkEISKIEWYKLSEL 231
Cdd:cd04670   73 RfgksdLYfVCRLRPlsdEEIKICPE---EIAEAKWMPLEEY 111

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 121 RGAIMLNQDmDEVVLVKgwKKGANWSFPRGKINKGEKDLDCAIREVYEETGFDVRQaglvkddenVKFIeitMREQ--HM 198
Cdd:cd04667    2 RATVICRRG-DRILLVA--RRGGRWLLPGGKIEPGESPLEAAIRELKEETGLAALS---------LLYL---FEHEgpHK 66

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 121713842 199 RLYVFR-GVPQDTHfePRTRKEISKIEWYKLSELPTLMKKN 238
Cdd:cd04667   67 LHHVFLaEAPDGGR--PRPGNEIARCRWVSADQLRDLNLSR 105

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 122 GAIMLNQDmdEVVLVK-------GWkkganWSFPRGKINKGEKDLDCAIREVYEETGFDVRQAGLV--------KDDENV 186
Cdd:cd04673    5 GAVVFRDG--RVLLVRrgnppdaGL-----WSFPGGKVELGETLEDAALRELREETGLEAEVVGLLtvvdvierDEAGRV 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 121713842 187 KFieitmreqHMRLYVFRGVPQDthFEPRTRKEISKIEWYKLSELPTL 234
Cdd:cd04673   78 RF--------HYVILDFLAEWVS--GEPVAGDDALDARWFSLEELDGL 115

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 117 RVPVrGAIMLNqDMDEVVLvkGWKKGA----NWSFPRGKINKGEKDLDCAIREVYEETGFDVRqaglvkddeNVKFIEIT 192
Cdd:cd04678    2 RVGV-GVIVLN-DDGKVLL--GRRKGShgagTWALPGGHLEFGESFEECAAREVLEETGLEIR---------NVRFLTVT 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 121713842 193 M----REQHMRLYVF-RGVPQDThfEPRTRKEISKIE---WYKLSELPTLMK 236
Cdd:cd04678   69 NdvfeEEGKHYVTIFvLAEVDDG--EPEENMEPDKCEgweWFSWDELPPLRP 118

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 121713842 118 VPVRGAIMLNQDMDeVVLVKGWKKGANWSFPRGKINKGEKDLDCAIREVYEETGFDVR 175
Cdd:cd18874    2 EPTVGALIFNPDGK-VLLVRSHKWNDLYGIPGGKVEWGETLEEALKREVKEETGLDIT 58

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 118 VPVRGAImlnQDMDEVVLVKGwKKGANWSFPRGKINKGEKDLDCAIREVYEETGFDVRQAGLVKDDENVKFIEITMREQH 197
Cdd:cd18891    3 VDVRAFI---QNENKVLLVQD-KHTKEWALPGGFAEVGLSPKENILKEVKEETGLHVEVERLLAVFDTDLRQDIPQSFQY 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 121713842 198 MRLyVFRGVPQDTHFEPrtRKEISKIEWYKLSELPTLMKK 237
Cdd:cd18891   79 YKF-IFACKILDGEFQE--NSETSDLQYFSLDQLPNLSLK 115

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 122 GAIMLNQDmDEVVLVKGWKKGANWSFPRGKINKGEKDLDCAIREVYEETGFDVRQAGLVK-----------DDENVKFIE 190
Cdd:cd03671    7 GIVLFNRD-GQVLVGRRIDVPGAWQFPQGGIDEGEDPEEAALRELYEETGLSPEDVEIIAetpdwltydlpEDLIRKGWG 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 121713842 191 ITMREQHMRLYVFR--GVPQDTHFEPRTRKEISKIEWYKLSELPTL 234
Cdd:cd03671   86 GKYRGQKQKWFLFRftGDDSEINLDTHEHPEFDAWRWVDLEELPDL 131

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 117 RVPVRGAIMLNqdmDEVVLVKGWK-KGANWSFPRGKINKGEKDLDCAIREVYEETGFDVR 175
Cdd:cd18880    1 RIRAKAIIIED---GKLLLVKHRDeGGIFYILPGGGQEHGETLPEALKRECLEETGLDVE 57

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 120 VRGAImLNqDMDEVVLVK-GWKKGanWSFPRGKINKGEKDLDCAIREVYEETGFDVRQAGLVKddeNVKFIEITMREQHM 198
Cdd:cd04680    3 VRAIV-LD-DAGRVLLVRhTYVPG--WYLPGGGVDKGETAEEAARRELREEAGVVLTGPPRLF---GVYFNRRVSPRDHV 75

                         90       100       110
                 ....*....|....*....|....*....|....
gi 121713842 199 RLYVFRGVPQDTHFEPrtRKEISKIEWYKLSELP 232
Cdd:cd04680   76 ALYRVREFEQTEPPEP--NGEIAEAGFFALDALP 107

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.

                         10        20
                 ....*....|....*....|....*..
gi 121713842 145 WSFPRGKINKGEKDLDCAIREVYEETG 171
Cdd:cd04665   24 WEFPGGKREPGETIEEAARRELYEETG 50

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 120 VRGAIMLNQDmDEVVLVKGWKKGAN-WSFPRGKINKGEKDLDCAIREVYEETGFDVR-QAGLVKDDENVKfieitmREQH 197
Cdd:cd04669    1 VRAVLVIYDD-DKLLLIRRTKPGEEyYVFPGGGIEPGETPEEAALREAVEELGLDVAvTLITLILRVLND------GTQH 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 121713842 198 MRL-YVFRGVPQDTHFEPRTRKEIS--KIEWYKLSELPTL 234
Cdd:cd04669   74 YFLaRVITGSFGLGTGPEFERPERGtyEPVWVPLTALPAL 113

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 121713842 121 RGAIML--NQDMDEVVLVKGWKKGAN---WSFPRGKINKGEKDLDCAIREVYEETGFDVRQ 176
Cdd:cd24156    2 RGAVMIvpILDDDHLLLIREYAAGTEryeLGFPKGLIDPGETPEEAANRELKEEIGFGARQ 62

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842 123 AIMLNQDmDEVVLVKgwKKGAN-WSFPRGKINKGEKDLDCAIREVYEETGFDVrqaglvkDDENVKFI-----------E 190
Cdd:cd04690    5 AVIIIKD-GRLLLVR--KRGTDaFYLPGGKREPGETPLQALVRELKEELGLDL-------DPDSLRFLgtfeapaanepG 74

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 121713842 191 ITmreqhMRLYVFRGvpqDTHFEPRTRKEISKIEW 225
Cdd:cd04690   75 TT-----VRMTCFTA---DYDGEPQPAAEIEELRW 101

RNA pyrophosphohydrolase; Reviewed

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 121713842 122 GAIMLNQDmDEVVLVKGWKKGANWSFPRGKINKGEKDLDCAIREVYEETG 171
Cdd:PRK00714  12 GIILLNRQ-GQVFWGRRIGQGHSWQFPQGGIDPGETPEQAMYRELYEEVG 60

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  337 LSAQNPLAPSTTLQADTSKSNALLQLL-RSGSSREPTPQAPAIDRATHPNAVSGIHPPTHQPESLLAPNffpgfpqqfnq 415
Cdd:PHA03307   36 LSGSQGQLVSDSAELAAVTVVAGAAACdRFEPPTGPPPGPGTEAPANESRSTPTWSLSTLAPASPAREG----------- 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  416 adQPENLPRIPRKPYHGTAPPSLPMSTHPYASNEPSPPFGYHGLPqfqnRHGPEIHALSQTHRPAPAPAPYQQTGDPQFS 495
Cdd:PHA03307  105 --SPTPPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPP----PAASPPAAGASPAAVASDAASSRQAALPLSS 178

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  496 QPAHAPQIQGATVPPASNLPPPKLTShslallnvfkdnstRSPQPSNPSLVQRSEQTIM--AKPKTLHHQDQLLGLLKGA 573
Cdd:PHA03307  179 PEETARAPSSPPAEPPPSTPPAAASP--------------RPPRRSSPISASASSPAPApgRSAADDAGASSSDSSSSES 244

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  574 PPSAPAELSAQPVSPAGKRILQRSRAEPSTPKRSASHMSTMPKGDPrtsatasgaasgaPNVTHPEPNFRGPVKKMQNGS 653
Cdd:PHA03307  245 SGCGWGPENECPLPRPAPITLPTRIWEASGWNGPSSRPGPASSSSS-------------PRERSPSPSPSSPGSGPAPSS 311

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121713842  654 NRKNKDRQTQPLASPITILSRPQSGRKE-SSPTPVISRSPKP----PSRASSQPRTNKPKAAEPSKPFQPQILRRSdnls 728
Cdd:PHA03307  312 PRASSSSSSSRESSSSSTSSSSESSRGAaVSPGPSPSRSPSPsrppPPADPSSPRKRPRPSRAPSSPAASAGRPTR---- 387

                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*.
gi 121713842  729 ldnilPTRSKDNDGPSQQTAGPPPNDGQGTKPAQANFDRRPSQTVA 774
Cdd:PHA03307  388 -----RRARAAVAGRARRRDATGRFPAGRPRPSPLDAGAASGAFYA 428