25 kDa subunit of cleavage factor Im; Precursor mRNA (pre-mRNA) cleavage factor I(m) (also called NUDIX (nucleoside diphosphate linked moiety X))-type motif 21) is a oligomer composed of a small 25 kDa subunit (CF I(m)25) and a variable larger subunit of either 59, 68 or 72 kDa and plays an important role in pre-mRNA 3'-end cleavage and the selection of poly(A) sites in a 3'-untranslated region (3'-UTR) of mRNA, producing mRNAs with variable 3' ends. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein and belongs to the NUDIX hydrolase superfamily. NUDIX hydrolases are 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74858879  12 NTSYSFGK-EEKKEKEQSLTSKLARLKDSYEKEGLRKAVEGIIIIHDHGHPHILLLQ-DNNYFKLPGGKLKPGENEIDGL 89
Cdd:cd18871   4 LTNYTFGTkEAKVEKDSSVAARLQRLKEEYEKDGMRRTVEGVLLVHEHGHPHVLLLQlGNSFFKLPGGRLRPGEDEVEGL 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74858879  90 IRKLTKKLSPTGTPVsDAPWEIGDHVSTWWRPNFEPSLFPYIPSHITKPKECKKLFVVTLPEKCKFAVSNNLSLIAVSLY 169
Cdd:cd18871  84 KRKLTEKLSPEDSEV-LNDWEIGDCLGVWWRPNFETPMYPYLPAHITKPKECKKLYLVQLPEKCLFAVPKNYKLLAVPLF 162

                       170       180
                ....*....|....*....|..
gi 74858879 170 EIYNNSQRYGAVISSIPALISR 191
Cdd:cd18871 163 ELYDNAARYGPIISSLPQLLSR 184

25 kDa subunit of cleavage factor Im; Precursor mRNA (pre-mRNA) cleavage factor I(m) (also called NUDIX (nucleoside diphosphate linked moiety X))-type motif 21) is a oligomer composed of a small 25 kDa subunit (CF I(m)25) and a variable larger subunit of either 59, 68 or 72 kDa and plays an important role in pre-mRNA 3'-end cleavage and the selection of poly(A) sites in a 3'-untranslated region (3'-UTR) of mRNA, producing mRNAs with variable 3' ends. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein and belongs to the NUDIX hydrolase superfamily. NUDIX hydrolases are 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74858879  12 NTSYSFGK-EEKKEKEQSLTSKLARLKDSYEKEGLRKAVEGIIIIHDHGHPHILLLQ-DNNYFKLPGGKLKPGENEIDGL 89
Cdd:cd18871   4 LTNYTFGTkEAKVEKDSSVAARLQRLKEEYEKDGMRRTVEGVLLVHEHGHPHVLLLQlGNSFFKLPGGRLRPGEDEVEGL 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74858879  90 IRKLTKKLSPTGTPVsDAPWEIGDHVSTWWRPNFEPSLFPYIPSHITKPKECKKLFVVTLPEKCKFAVSNNLSLIAVSLY 169
Cdd:cd18871  84 KRKLTEKLSPEDSEV-LNDWEIGDCLGVWWRPNFETPMYPYLPAHITKPKECKKLYLVQLPEKCLFAVPKNYKLLAVPLF 162

                       170       180
                ....*....|....*....|..
gi 74858879 170 EIYNNSQRYGAVISSIPALISR 191
Cdd:cd18871 163 ELYDNAARYGPIISSLPQLLSR 184

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 74858879   63 ILLLQDNNY------FKLPGGKLKPGENEIDGLIRKLTKKLSPTGTP---VSDAPWEIGD---HVSTWWRPNF 123
Cdd:PRK10546  17 ILLAQRPAHsdqaglWEFAGGKVEPGESQPQALIRELREELGIEATVgeyVASHQREVSGrriHLHAWHVPDF 89

25 kDa subunit of cleavage factor Im; Precursor mRNA (pre-mRNA) cleavage factor I(m) (also called NUDIX (nucleoside diphosphate linked moiety X))-type motif 21) is a oligomer composed of a small 25 kDa subunit (CF I(m)25) and a variable larger subunit of either 59, 68 or 72 kDa and plays an important role in pre-mRNA 3'-end cleavage and the selection of poly(A) sites in a 3'-untranslated region (3'-UTR) of mRNA, producing mRNAs with variable 3' ends. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein and belongs to the NUDIX hydrolase superfamily. NUDIX hydrolases are 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74858879  12 NTSYSFGK-EEKKEKEQSLTSKLARLKDSYEKEGLRKAVEGIIIIHDHGHPHILLLQ-DNNYFKLPGGKLKPGENEIDGL 89
Cdd:cd18871   4 LTNYTFGTkEAKVEKDSSVAARLQRLKEEYEKDGMRRTVEGVLLVHEHGHPHVLLLQlGNSFFKLPGGRLRPGEDEVEGL 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74858879  90 IRKLTKKLSPTGTPVsDAPWEIGDHVSTWWRPNFEPSLFPYIPSHITKPKECKKLFVVTLPEKCKFAVSNNLSLIAVSLY 169
Cdd:cd18871  84 KRKLTEKLSPEDSEV-LNDWEIGDCLGVWWRPNFETPMYPYLPAHITKPKECKKLYLVQLPEKCLFAVPKNYKLLAVPLF 162

                       170       180
                ....*....|....*....|..
gi 74858879 170 EIYNNSQRYGAVISSIPALISR 191
Cdd:cd18871 163 ELYDNAARYGPIISSLPQLLSR 184

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 74858879  48 AVEGIIIiHDHghpHILLLQ----DNNYFKLPGGKLKPGENEIDGLIR 91
Cdd:cd04699   4 SVKGVIF-DNG---RVLLLRrsraGAGEWELPGGRLEPGESPEEALKR 47

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 74858879  51 GIIIIHDHGHPHILLLQDN-------NYFKLPGGKLKPGENEIDGLIRKL 93
Cdd:cd18882   4 AIAILYDDRGKVLLQLRDDkpgipypGYWGLFGGHLEPGETPEEAIRREL 53

pyrimidine (deoxy)nucleoside triphosphate diphosphatase;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 74858879   63 ILLLQDNNY------FKLPGGKLKPGENEIDGLIRKLTKKLSPTGTP---VSDAPWEIGD---HVSTWWRPNF 123
Cdd:PRK10546  17 ILLAQRPAHsdqaglWEFAGGKVEPGESQPQALIRELREELGIEATVgeyVASHQREVSGrriHLHAWHVPDF 89

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
                ....*....|....*....|....*....|....*....|....*
gi 74858879  51 GIIIIHDHGHphILLLQD----NNYFKLPGGKLKPGENEIDGLIR 91
Cdd:cd04670   6 GGLVINENNE--VLVVQEkyggPGGWKLPGGLVDPGEDIGEAAVR 48

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 74858879  53 IIIHDHGHphILLLQ-----DNNYFKLPGGKLKPGENEIDGLIRKL 93
Cdd:COG1051  12 VIFRKDGR--VLLVRradepGKGLWALPGGKVEPGETPEEAALREL 55

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 74858879  46 RKAVEGIIiihDHGHPHILLLQD-NNYFKLPGGKLKPGENEIDGLIRKL 93
Cdd:cd04684  15 RPGAYAVI---FNDEGKVLLVQTpNGGYFLPGGGIEPGETPEEALHREV 60