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 303279404  13 VYPVTNYSFGQKAGRAAKDATPSATATRLREAYERDGPRRSVDAVMLVNQHNTPHVLLLQSAgsgpgaPATFRLPGGRLR 92
Cdd:cd18871    1 IYPLTNYTFGTKEAKVEKDSSVAARLQRLKEEYEKDGMRRTVEGVLLVHEHGHPHVLLLQLG------NSFFKLPGGRLR 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 303279404  93 RGEGELEGLQRKLHSKLSPSDAslGGAKEWETGDCLARWHRPAHDAHFYPYLPTHATRPKEARAVYAVQLPEKCKFAVPK 172
Cdd:cd18871   75 PGEDEVEGLKRKLTEKLSPEDS--EVLNDWEIGDCLGVWWRPNFETPMYPYLPAHITKPKECKKLYLVQLPEKCLFAVPK 152

                        170       180       190
                 ....*....|....*....|....*....|..
gi 303279404 173 SLKLLAVPLFELYGNEKRYGAVVSSIPYLISR 204
Cdd:cd18871  153 NYKLLAVPLFELYDNAARYGPIISSLPQLLSR 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 303279404  13 VYPVTNYSFGQKAGRAAKDATPSATATRLREAYERDGPRRSVDAVMLVNQHNTPHVLLLQSAgsgpgaPATFRLPGGRLR 92
Cdd:cd18871    1 IYPLTNYTFGTKEAKVEKDSSVAARLQRLKEEYEKDGMRRTVEGVLLVHEHGHPHVLLLQLG------NSFFKLPGGRLR 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 303279404  93 RGEGELEGLQRKLHSKLSPSDAslGGAKEWETGDCLARWHRPAHDAHFYPYLPTHATRPKEARAVYAVQLPEKCKFAVPK 172
Cdd:cd18871   75 PGEDEVEGLKRKLTEKLSPEDS--EVLNDWEIGDCLGVWWRPNFETPMYPYLPAHITKPKECKKLYLVQLPEKCLFAVPK 152

                        170       180       190
                 ....*....|....*....|....*....|..
gi 303279404 173 SLKLLAVPLFELYGNEKRYGAVVSSIPYLISR 204
Cdd:cd18871  153 NYKLLAVPLFELYDNAARYGPIISSLPQLLSR 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 303279404  13 VYPVTNYSFGQKAGRAAKDATPSATATRLREAYERDGPRRSVDAVMLVNQHNTPHVLLLQSAgsgpgaPATFRLPGGRLR 92
Cdd:cd18871    1 IYPLTNYTFGTKEAKVEKDSSVAARLQRLKEEYEKDGMRRTVEGVLLVHEHGHPHVLLLQLG------NSFFKLPGGRLR 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 303279404  93 RGEGELEGLQRKLHSKLSPSDAslGGAKEWETGDCLARWHRPAHDAHFYPYLPTHATRPKEARAVYAVQLPEKCKFAVPK 172
Cdd:cd18871   75 PGEDEVEGLKRKLTEKLSPEDS--EVLNDWEIGDCLGVWWRPNFETPMYPYLPAHITKPKECKKLYLVQLPEKCLFAVPK 152

                        170       180       190
                 ....*....|....*....|....*....|..
gi 303279404 173 SLKLLAVPLFELYGNEKRYGAVVSSIPYLISR 204
Cdd:cd18871  153 NYKLLAVPLFELYDNAARYGPIISSLPQLLSR 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
                 ....*....|....*....|....*....|....*..
gi 303279404  67 HVLLLQSAGSGPGapaTFRLPGGRLRRGEGELEGLQR 103
Cdd:cd04699   14 RVLLLRRSRAGAG---EWELPGGRLEPGESPEEALKR 47