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 307107193   1 VYPVGNYTFGSKPPKFEKDSSVTQRLERLKEKYAREGLRRSVEAVLVVHEHGHPHVLVLQMGASFFKLPGGRLRPGEDEA 80
Cdd:cd18871    1 IYPLTNYTFGTKEAKVEKDSSVAARLQRLKEEYEKDGMRRTVEGVLLVHEHGHPHVLLLQLGNSFFKLPGGRLRPGEDEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307107193  81 EGMLRKLHSLLAPPAENMRPDWRVSDLLGTWWRPNFENMMYPYCPAHVARPKEVKRLFLIALPERCYLSVPKNMRLVAVP 160
Cdd:cd18871   81 EGLKRKLTEKLSPEDSEVLNDWEIGDCLGVWWRPNFETPMYPYLPAHITKPKECKKLYLVQLPEKCLFAVPKNYKLLAVP 160

                        170       180
                 ....*....|....*....|....
gi 307107193 161 LFELYDNISRYGPVISSIPALLSR 184
Cdd:cd18871  161 LFELYDNAARYGPIISSLPQLLSR 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 307107193   1 VYPVGNYTFGSKPPKFEKDSSVTQRLERLKEKYAREGLRRSVEAVLVVHEHGHPHVLVLQMGASFFKLPGGRLRPGEDEA 80
Cdd:cd18871    1 IYPLTNYTFGTKEAKVEKDSSVAARLQRLKEEYEKDGMRRTVEGVLLVHEHGHPHVLLLQLGNSFFKLPGGRLRPGEDEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307107193  81 EGMLRKLHSLLAPPAENMRPDWRVSDLLGTWWRPNFENMMYPYCPAHVARPKEVKRLFLIALPERCYLSVPKNMRLVAVP 160
Cdd:cd18871   81 EGLKRKLTEKLSPEDSEVLNDWEIGDCLGVWWRPNFETPMYPYLPAHITKPKECKKLYLVQLPEKCLFAVPKNYKLLAVP 160

                        170       180
                 ....*....|....*....|....
gi 307107193 161 LFELYDNISRYGPVISSIPALLSR 184
Cdd:cd18871  161 LFELYDNAARYGPIISSLPQLLSR 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 307107193   1 VYPVGNYTFGSKPPKFEKDSSVTQRLERLKEKYAREGLRRSVEAVLVVHEHGHPHVLVLQMGASFFKLPGGRLRPGEDEA 80
Cdd:cd18871    1 IYPLTNYTFGTKEAKVEKDSSVAARLQRLKEEYEKDGMRRTVEGVLLVHEHGHPHVLLLQLGNSFFKLPGGRLRPGEDEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307107193  81 EGMLRKLHSLLAPPAENMRPDWRVSDLLGTWWRPNFENMMYPYCPAHVARPKEVKRLFLIALPERCYLSVPKNMRLVAVP 160
Cdd:cd18871   81 EGLKRKLTEKLSPEDSEVLNDWEIGDCLGVWWRPNFETPMYPYLPAHITKPKECKKLYLVQLPEKCLFAVPKNYKLLAVP 160

                        170       180
                 ....*....|....*....|....
gi 307107193 161 LFELYDNISRYGPVISSIPALLSR 184
Cdd:cd18871  161 LFELYDNAARYGPIISSLPQLLSR 184

bifunctional NMN adenylyltransferase/ADP-ribose pyrophosphatase and similar proteins; Bacterial NadM-Nudix is a bifunctional enzyme containing a nicotinamide mononucleotide (NMN) adenylyltransferase (NMNAT) and an ADP-ribose pyrophosphatase (ADPRase) domain. NMNAT was initially identified as an NAD+ synthase that catalyzes the reversible conversion of NMN to NAD+ in the final step of both the de novo biosynthesis and salvage pathways in most organisms across all three kingdoms of life ADPRase is a member of the NUDIX family proteins, catalyzes the metal-induced and concerted general acid-base hydrolysis of ADP ribose (ADPR) into AMP and ribose-5'-phosphate (R5P). Additional members in this cd include bacterial transcriptional regulator, NrtR, which represses the transcription of NAD biosynthetic genes in vitro and adenosine diphosphate ribose (ADPR), as well as NadQ, a NUDIX-like ATP-responsive regulator of NAD biosynthesis. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belong to this superfamily requires a divalent cation, such as Mg2+ or Mn2+ for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, U=I, L or V) which functions as 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 _ "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 307107193  44 AVLVVHEHGhPHVLVLQMGASFFK----LPGGRLRPGEDEAEGMLRKLH 88
Cdd:cd18873    8 VIFGFDDGE-LKVLLIKRKNEPFKggwaLPGGFVREDETLEDAARRELR 55