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 755502681 145 DTAVREVFEETGVKSEFRSLLSIRQQHrsPGAFGMSDMYLVCRLQPRSFT-INFCQQECLKCEWIDLENLARTKHTTPIT 223
Cdd:cd04670   44 EAAVREVFEETGIDTEFVSILGFRHQH--PGRFGKSDLYFVCRLRPLSDEeIKICPEEIAEAKWMPLEEYLKQPNVSQIN 121

                 ....*....
gi 755502681 224 SRVARLLLY 232
Cdd:cd04670  122 KLVAKLLLE 130

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 755502681 145 DTAVREVFEETGVKSEFRSLLSIRQQHrsPGAFGMSDMYLVCRLQPRSFT-INFCQQECLKCEWIDLENLARTKHTTPIT 223
Cdd:cd04670   44 EAAVREVFEETGIDTEFVSILGFRHQH--PGRFGKSDLYFVCRLRPLSDEeIKICPEEIAEAKWMPLEEYLKQPNVSQIN 121

                 ....*....
gi 755502681 224 SRVARLLLY 232
Cdd:cd04670  122 KLVAKLLLE 130

NUDIX domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 755502681  143 VADTAVREVFEETGVKSEFRSLL-SIRQQHRSPGAFGMSDMYLVCRLQPRSFTINFCQ-QECLKCEWIDLENLARTKH 218
Cdd:pfam00293  44 PEEAARRELEEETGLEPELLELLgSLHYLAPFDGRFPDEHEILYVFLAEVEGELEPDPdGEVEEVRWVPLEELLLLKL 121

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 755502681 145 DTAVREVFEETGVKSEFRSLLSIRQQHrsPGAFGMSDMYLVCRLQPRSFT-INFCQQECLKCEWIDLENLARTKHTTPIT 223
Cdd:cd04670   44 EAAVREVFEETGIDTEFVSILGFRHQH--PGRFGKSDLYFVCRLRPLSDEeIKICPEEIAEAKWMPLEEYLKQPNVSQIN 121

                 ....*....
gi 755502681 224 SRVARLLLY 232
Cdd:cd04670  122 KLVAKLLLE 130

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755502681 127 GEGPSRLPGYATHQVGVADTAV-REVFEETGVKSEFRSLLSIRQQhrsPGAFGMSDMYLVCRLQPRSFTINFCQQECLKC 205
Cdd:cd04691   24 GKGRWTLPGGFVEEGETLDEAIvREVLEETGIDAKPVGIIGVRSG---VIRDGKSDNYVVFLLEYVGGEPKPDERENSEA 100

                         90
                 ....*....|....*...
gi 755502681 206 EWIDLENLARTKHTTPIT 223
Cdd:cd04691  101 GFLTLEEALANEDIADMS 118

NUDIX domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 755502681  143 VADTAVREVFEETGVKSEFRSLL-SIRQQHRSPGAFGMSDMYLVCRLQPRSFTINFCQ-QECLKCEWIDLENLARTKH 218
Cdd:pfam00293  44 PEEAARRELEEETGLEPELLELLgSLHYLAPFDGRFPDEHEILYVFLAEVEGELEPDPdGEVEEVRWVPLEELLLLKL 121

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 755502681 144 ADTAVREVFEETGVKSEFRSLLSIRQQHRSPGAFGMSDMYLVCRLQPRsFTINFCQQECLKCEWID 209
Cdd:cd02883   42 EEAAVREVREETGLDVEVLRLLGVYEFPDPDEGRHVVVLVFLARVVGG-EPPPLDDEEISEVRWVP 106

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 755502681 143 VADTAVREVFEETGVKSEFRSLLSIrqqHRSPGAFGMSDMYLVCRLQPRSFTINfcqQECLKCEWIDLENLA 214
Cdd:COG1051   47 PEEAALRELREETGLEVEVLELLGV---FDHPDRGHVVSVAFLAEVLSGEPRAD---DEIDEARWFPLDELP 112

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 755502681 144 ADTAVREVFEETG------VKSEFRSLLSIRQQHRSpgafgmsdMYLvCRLQPRSFtiNFCQQ---ECLKCEWIDLENLA 214
Cdd:cd03672   42 ADCAIREVYEETGfdisdlINDKDYIELTINGQRVR--------LYI-IPGVPEDT--PFEPQtrkEISKIEWFDIDDLP 110

                 ...
gi 755502681 215 RTK 217
Cdd:cd03672  111 KNK 113