Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596  16 FHCSAAEG--DIAKLtgILSHSPSLlNETSENGWTALMYAARNGHPEIVQFLLEKGCDRSIVNKSRQTALDIAVFWGYKH 93
Cdd:COG0666   157 LHLAAANGnlEIVKL--LLEAGADV-NARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLE 233

                          90
                  ....*....|....*
gi 2462604596  94 IANLLATAKGGKKPW 108
Cdd:COG0666   234 IVKLLLEAGADLNAK 248

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596 322 DPVVIMQVIHPDGtKCLLGRQKRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVACQPWPMPSSLMIGCL 401
Cdd:cd03429     1 DPAVIVLVTNGED-KILLARQPRWPPGRYSLLAGFVEPGETLEEAVRREVKEEVGLRVKNVRYVGSQPWPFPSSLMLGFT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2462604596 402 ALAVSTEIKVDKNEIEDARWFTREQVLDVLtkgkqqafFVPPSRAIAHQLIKHWI 456
Cdd:cd03429    80 AEADSGEITVDDDELEDARWFSRDELPEAL--------FLPPPGSIARRLIRAWL 126

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596 329 VIHPDGTKCLLGRQ-KRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVACQ--------PWPMPSSLMIG 399
Cdd:pfam00293   9 VLLNEKGRVLLVRRsKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPELLELLGSLhylapfdgRFPDEHEILYV 88

                          90       100
                  ....*....|....*....|....*....
gi 2462604596 400 CLALAVSTEIKVDKNEIEDARWFTREQVL 428
Cdd:pfam00293  89 FLAEVEGELEPDPDGEVEEVRWVPLEELL 117

Ankyrin repeats (3 copies);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596  16 FHCSAAEGDIAKLTGILSHSPSLlNETSENGWTALMYAARNGHPEIVQFLLEKgCDRSIVNKSRqTALDIAVFWGYKHIA 95
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADA-NLQDKNGRTALHLAAKNGHLEIVKLLLEH-ADVNLKDNGR-TALHYAARSGHLEIV 77

                  ...
gi 2462604596  96 NLL 98
Cdd:pfam12796  78 KLL 80

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.

                           10        20
                   ....*....|....*....|....*..
gi 2462604596   45 NGWTALMYAARNGHPEIVQFLLEKGCD 71
Cdd:smart00248   1 DGRTPLHLAAENGNLEVVKLLLDKGAD 27

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596 322 DPVVIMQVIHPDGtKCLLGRQKRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVACQPWPMPSSLMIGCL 401
Cdd:cd03429     1 DPAVIVLVTNGED-KILLARQPRWPPGRYSLLAGFVEPGETLEEAVRREVKEEVGLRVKNVRYVGSQPWPFPSSLMLGFT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2462604596 402 ALAVSTEIKVDKNEIEDARWFTREQVLDVLtkgkqqafFVPPSRAIAHQLIKHWI 456
Cdd:cd03429    80 AEADSGEITVDDDELEDARWFSRDELPEAL--------FLPPPGSIARRLIRAWL 126

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596 329 VIHPDGtKCLLGRQKRFP-PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVACQPWPMPSS-LMIGCLALAVS 406
Cdd:COG1051    13 IFRKDG-RVLLVRRADEPgKGLWALPGGKVEPGETPEEAALRELREETGLEVEVLELLGVFDHPDRGHvVSVAFLAEVLS 91

                          90       100
                  ....*....|....*....|...
gi 2462604596 407 TEIKVDkNEIEDARWFTREQVLD 429
Cdd:COG1051    92 GEPRAD-DEIDEARWFPLDELPE 113

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 2462604596 329 VIHPDGTKCLLGRQKRFP-PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVACQPWPMP----SSLMIGCLAL 403
Cdd:cd02883     6 VVFDDEGRVLLVRRSDGPgPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPdegrHVVVLVFLAR 85

                          90       100
                  ....*....|....*....|.
gi 2462604596 404 AVSTEIKV-DKNEIEDARWFT 423
Cdd:cd02883    86 VVGGEPPPlDDEEISEVRWVP 106

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596  14 TQFHCSAAEG--DIAKLtgilshspsLL------NETSENGWTALMYAARNGHPEIVQFLLEKGCDRSIVNKSRQTALDI 85
Cdd:COG0666   122 TPLHLAAYNGnlEIVKL---------LLeagadvNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHL 192

                          90
                  ....*....|...
gi 2462604596  86 AVFWGYKHIANLL 98
Cdd:COG0666   193 AAENGHLEIVKLL 205

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596 324 VVImqVIHPDGTKCLLGRQKRFP--PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVACQPWP-MPSSLMIGC 400
Cdd:COG0494    16 VVV--VLLDDDGRVLLVRRYRYGvgPGLWEFPGGKIEPGESPEEAALRELREETGLTAEDLELLGELPSPgYTDEKVHVF 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2462604596 401 LALAVSTEIKV---DKNEIEDARWFTREQVLDVLTKGKQQA 438
Cdd:COG0494    94 LARGLGPGEEVgldDEDEFIEVRWVPLDEALALVTAGEIAK 134

Ankyrin repeats (3 copies);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596  16 FHCSAAEGDIAKLTGILSHSPSLlNETSENGWTALMYAARNGHPEIVQFLLEKgCDRSIVNKSRqTALDIAVFWGYKHIA 95
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADA-NLQDKNGRTALHLAAKNGHLEIVKLLLEH-ADVNLKDNGR-TALHYAARSGHLEIV 77

                  ...
gi 2462604596  96 NLL 98
Cdd:pfam12796  78 KLL 80

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 2462604596 329 VIHPDGtKCLLGRQKRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVA-CQPWPMP---SSLMIGCLALA 404
Cdd:cd04670     9 VINENN-EVLVVQEKYGGPGGWKLPGGLVDPGEDIGEAAVREVFEETGIDTEFVSILGfRHQHPGRfgkSDLYFVCRLRP 87

                          90       100
                  ....*....|....*....|....*.
gi 2462604596 405 VS-TEIKVDKNEIEDARWFTREQVLD 429
Cdd:cd04670    88 LSdEEIKICPEEIAEAKWMPLEEYLK 113

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596 329 VIHPDGTKCLLGR----QKRFPPGmftclaGFIEPGETIEDAVRREVEEESGVKVGHVQYVACQPW-----PMPSSLMIG 399
Cdd:cd03674     8 VVNPDRGKVLLVHhrklGRWLQPG------GHVEPDEDPLEAALREAREETGLDVELLSPLSPDPLdidvhPIPANPGEP 81

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462604596 400 C--------LALAVSTEIKVDKNEIEDARWFTREQVLD 429
Cdd:cd03674    82 AhlhldvryLAVADGDEALRKSDESSDVRWFPLDELEE 119

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596 324 VVIMqVIHPDGtKCLLGRQKRFPPGMFTcL---AGFIEPGETIEDAVRREVEEESGVKVGHVQYVACqPWPMP---SSLM 397
Cdd:cd03424     5 VAVL-AITDDG-KVVLVRQYRHPVGRVL-LelpAGKIDPGEDPEEAARRELEEETGYTAGDLELLGS-FYPSPgfsDERI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2462604596 398 IGCLA--LAVSTEIKVDKNEIEDARWFTREQVLDVLTKGK 435
Cdd:cd03424    81 HLFLAedLTPVSEQALDEDEFIEVVLVPLEEALEMIEDGE 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596 347 PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVACQPWPMPSSLMIGCL--ALAVSTEIkVDKNEIEDARWFTR 424
Cdd:cd18882    29 PGYWGLFGGHLEPGETPEEAIRRELEEEIGYEPGEFRFFLLYTEDDGEDRIRHVFhaPLDVDLSD-LVLNEGQALRLFSP 107

                  ....*
gi 2462604596 425 EQVLD 429
Cdd:cd18882   108 EEILQ 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462604596 333 DGTKCLLGRQKR-FPPGMFTCLAGFIEPGETIEDAVRREVEEESGV------KVGHVQYV-ACQPWPM 392
Cdd:cd03427    11 GDDRVLLGLKKRgFGAGKWNGFGGKVEPGETIEEAAVRELEEEAGLtateleKVGRLKFEfPDDPEAM 78

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462604596 338 LLGRQKRFP-------PGMFTCLAGFIEPGETIEDAVRREVEEESGVKVGHVQYVaCQPWPMP 393
Cdd:cd24155    59 VLIEQFRIGalardesPWLLEIVAGMIDAGETPEDVARREAEEEAGLTLDALEPI-ASYYPSP 120

Ankyrin repeats (3 copies);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462604596  17 HCSAAEG--DIAKLtgILSHSPSllnETSENGWTALMYAARNGHPEIVQFLLEKGCD 71
Cdd:pfam12796  35 HLAAKNGhlEIVKL--LLEHADV---NLKDNGRTALHYAARSGHLEIVKLLLEKGAD 86

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462604596 319 PRVDPVVImqVIHPDGtKCLLGRQK-RFPPGMFtCLA-GFIEPGETIEDAVRREVEEESGVKVGHVQYVAC 387
Cdd:cd04678     1 PRVGVGVI--VLNDDG-KVLLGRRKgSHGAGTW-ALPgGHLEFGESFEECAAREVLEETGLEIRNVRFLTV 67

Ankyrin repeats (many copies);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462604596  46 GWTALMYAARNGHPEIVQFLLEKGCDRSIVNKSRQTALDIAVFWGYKHIANLL 98
Cdd:pfam13637   1 ELTALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFAASNGNVEVLKLL 53

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596 355 GFIEPGETIEDAVRREVEEESG--VKVGH---VQYVACQPWPMPSSLMI---GCLALAVSTEIKVDKNEIEDARWFTREQ 426
Cdd:cd18876    30 GVVEAGESPLQAARREVREELGldVPVGRllaVDWVPPAGGGDDAVLFVfdgGVLTPEQAAAIRLQDEELSAYRFVTPEE 109

                  ....*.
gi 2462604596 427 VLDVLT 432
Cdd:cd18876   110 AAELLP 115

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 2462604596 329 VIHPDGTKCLLGRqkRFPPGMFTCLAGFIEPGETIEDAVRREVEEESGVKV-----------GHVQYV---ACQpwpmps 394
Cdd:cd18879    24 VVLRDAGRVLLVR--RADNGRWTPVTGIVEPGEQPADAAVREVLEETGVDVeverlasvgasPPVTYPngdQCQ------ 95

                          90       100
                  ....*....|....*....|....*...
gi 2462604596 395 SLMIGCLALAVSTEIKVDKNEIEDARWF 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.

                          10        20
                  ....*....|....*....|....*..
gi 2462604596  45 NGWTALMYAARNGHPEIVQFLLEKGCD 71
Cdd:pfam13606   1 DGNTPLHLAARNGRLEIVKLLLENGAD 27

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596  39 LNETSENGWTALMYAARNGHPEIVQFLLEKGCDRSIVNKSRQTALDIAVFWGYKHIANLL 98
Cdd:PHA03100  185 INIKDVYGFTPLHYAVYNNNPEFVKYLLDLGANPNLVNKYGDTPLHIAILNNNKEIFKLL 244

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596 318 YPRVDPVVIMqVIHPDGTKCLLGRQKRFP------PGMFT--ClAGFIEpGETIEDAVRREVEEESGVKVGHVQYVAcQP 389
Cdd:cd24157     1 YDRGDAAAVL-LYDPKRKTVVLVRQFRAPaylgggDGWLIeaC-AGLLD-GDDPEDCIRREAEEETGYRLGDLEKVF-TA 76

                  ....*...
gi 2462604596 390 WPMPSSLM 397
Cdd:cd24157    77 YSSPGIVT 84

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462604596 354 AGFIEPGETIEDAVRREVEEESGVKVGHVQYVACQPWPMPSS------LMIGCLALAVSTEIKVDKnEIEDARWFTREQV 427
Cdd:cd03675    30 AGHLEPGESLLEAAIRETLEETGWEVEPTALLGIYQWTAPDNgvtylrFAFAGELLEHLPDQPLDS-GIIRAHWLTLEEI 108

                  ..
gi 2462604596 428 LD 429
Cdd:cd03675   109 LA 110

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 2462604596 354 AGFIEPGETIEDAVRREVEEESGVKVG-------------HVQYvacqpwpmP-----SSLMIGCLALAVSTEIKVDKNE 415
Cdd:cd04677    41 GGAMELGESLEETARREVFEETGLTVEelellgvysgkdlYYTY--------PngdevYNVTAVYLVRDVSGELKVDDEE 112

                          90
                  ....*....|.
gi 2462604596 416 IEDARWFTREQ 426
Cdd:cd04677   113 SLELRFFSLDE 123