nucleoside diphosphate-linked moiety X)) motif 16; U8 SnoRNA-decapping enzyme, also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 16/Nudt16, is encoded by the human NUDT16 gene and a RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. 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 189011649  18 GWRHACHALLYAPDPRKLFGRIPMRFAVLMQMRFDGRLGFPGGFVDAQDScLEDGLNRELREELGDAVSAFRVERSDYQS 97
Cdd:cd18869    1 GYRHACHAMLYAPNPGKLFGRYPIRATLLMQMRFDGLLGFPGGFVDTGES-LEEGLNRELREELGLAHAVFPVTEDDYRS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189011649  98 SRIA-ARPRVVAHFYAKRLTLEQLQAVEARAPLAKDHGLEVLGLVRVPLYIMRDGEGGLPAFLENSFIGAAREQLLEALR 176
Cdd:cd18869   80 SHVReGPKRLVLHFYAKELSLEELDEIEIAAVNAKDHGLEVLGLIRVPLYTLRDGYGGLPTFLANSFIGNAREQLLEALI 159

                        170
                 ....*....|....*.
gi 189011649 177 DLKLLDPGTVAKLKIP 192
Cdd:cd18869  160 SLNLLPEEEITEALIA 175

nucleoside diphosphate-linked moiety X)) motif 16; U8 SnoRNA-decapping enzyme, also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 16/Nudt16, is encoded by the human NUDT16 gene and a RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. 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 189011649  18 GWRHACHALLYAPDPRKLFGRIPMRFAVLMQMRFDGRLGFPGGFVDAQDScLEDGLNRELREELGDAVSAFRVERSDYQS 97
Cdd:cd18869    1 GYRHACHAMLYAPNPGKLFGRYPIRATLLMQMRFDGLLGFPGGFVDTGES-LEEGLNRELREELGLAHAVFPVTEDDYRS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189011649  98 SRIA-ARPRVVAHFYAKRLTLEQLQAVEARAPLAKDHGLEVLGLVRVPLYIMRDGEGGLPAFLENSFIGAAREQLLEALR 176
Cdd:cd18869   80 SHVReGPKRLVLHFYAKELSLEELDEIEIAAVNAKDHGLEVLGLIRVPLYTLRDGYGGLPTFLANSFIGNAREQLLEALI 159

                        170
                 ....*....|....*.
gi 189011649 177 DLKLLDPGTVAKLKIP 192
Cdd:cd18869  160 SLNLLPEEEITEALIA 175

NUDIX domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 189011649   45 VLMQMR----FDGRLGFPGGFVDAQDScLEDGLNRELREELG---DAVSAFRVERSDYQSSRIAARPRVVAHFYAKRLT 116
Cdd:pfam00293  17 VLLVRRskkpFPGWWSLPGGKVEPGET-PEEAARRELEEETGlepELLELLGSLHYLAPFDGRFPDEHEILYVFLAEVE 94

nucleoside diphosphate-linked moiety X)) motif 16; U8 SnoRNA-decapping enzyme, also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 16/Nudt16, is encoded by the human NUDT16 gene and a RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. 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 189011649  18 GWRHACHALLYAPDPRKLFGRIPMRFAVLMQMRFDGRLGFPGGFVDAQDScLEDGLNRELREELGDAVSAFRVERSDYQS 97
Cdd:cd18869    1 GYRHACHAMLYAPNPGKLFGRYPIRATLLMQMRFDGLLGFPGGFVDTGES-LEEGLNRELREELGLAHAVFPVTEDDYRS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189011649  98 SRIA-ARPRVVAHFYAKRLTLEQLQAVEARAPLAKDHGLEVLGLVRVPLYIMRDGEGGLPAFLENSFIGAAREQLLEALR 176
Cdd:cd18869   80 SHVReGPKRLVLHFYAKELSLEELDEIEIAAVNAKDHGLEVLGLIRVPLYTLRDGYGGLPTFLANSFIGNAREQLLEALI 159

                        170
                 ....*....|....*.
gi 189011649 177 DLKLLDPGTVAKLKIP 192
Cdd:cd18869  160 SLNLLPEEEITEALIA 175

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 189011649  45 VLMQMR-------FDGRLGFPGGFVDAQDScLEDGLNRELREELGDAVSAFRVERSdYQSSRIAARPRvvaHFYAKRLTL 117
Cdd:cd18882   15 VLLQLRddkpgipYPGYWGLFGGHLEPGET-PEEAIRRELEEEIGYEPGEFRFFLL-YTEDDGEDRIR---HVFHAPLDV 89

                 ....
gi 189011649 118 EQLQ 121
Cdd:cd18882   90 DLSD 93

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 189011649  45 VLMQMR----FDGRLGFPGGFVDAQDScLEDGLNRELREELG 82
Cdd:COG1051   20 VLLVRRadepGKGLWALPGGKVEPGET-PEEAALRELREETG 60

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 189011649  20 RHACHALLYAPDPRklfgripmrfaVLMQMRFD-----GRLGFPGGFVDAQDScLEDGLNRELREELG 82
Cdd:COG0494   13 RPAVVVVLLDDDGR-----------VLLVRRYRygvgpGLWEFPGGKIEPGES-PEEAALRELREETG 68

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
                 ....*....|....*....|....*....|..
gi 189011649  51 FDGRLGFPGGFVDAQDScLEDGLNRELREELG 82
Cdd:cd18873   29 FKGGWALPGGFVREDET-LEDAARRELREETG 59