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 941510729  35 YYFNSSAATVAFILNDkNELLVCRRGKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEEAVYQFSLPNTYLYSG 114
Cdd:cd04681    1 YFHNVAAAVGVIIRNE-GEILFVRRAKEPGKGKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYLCSLPNTYLYKG 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 941510729 115 FLVHTLDQFFLCKVKDTSRI-KAMDDVAESFWLPLDEVNPEEFGLDSVREGVRRFL 169
Cdd:cd04681   80 ITYKTCDLFFTAELDEKPKLkKAEDEVAELEWLDLEEIEPEKLAFPSIRKAVERYI 135

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 941510729  35 YYFNSSAATVAFILNDkNELLVCRRGKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEEAVYQFSLPNTYLYSG 114
Cdd:cd04681    1 YFHNVAAAVGVIIRNE-GEILFVRRAKEPGKGKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYLCSLPNTYLYKG 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 941510729 115 FLVHTLDQFFLCKVKDTSRI-KAMDDVAESFWLPLDEVNPEEFGLDSVREGVRRFL 169
Cdd:cd04681   80 ITYKTCDLFFTAELDEKPKLkKAEDEVAELEWLDLEEIEPEKLAFPSIRKAVERYI 135

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941510729   41 AATVAFILNDKNELLVCRRGKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVE--EAVYQFSLPNTYLYSGFLVH 118
Cdd:pfam00293   4 VAVGVVLLNEKGRVLLVRRSKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPEllELLGSLHYLAPFDGRFPDEH 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 941510729  119 TLDQFFLCKVKDTSRIKAMDDVAESFWLPLDEVNPEEFGLDSvREGVRRF 168
Cdd:pfam00293  84 EILYVFLAEVEGELEPDPDGEVEEVRWVPLEELLLLKLAPGD-RKLLPWL 132

NADH pyrophosphatase zinc ribbon domain; This domain is found in between two duplicated NUDIX domains. It has a zinc ribbon structure.

                          10        20        30
                  ....*....|....*....|....*....|
gi 941510729    7 FKYCPKCGSPHFEVNNEKSKRCADCGFVYY 36
Cdd:pfam09297   3 HRFCGRCGAPTVPAEGGWARVCPSCGHEHY 32

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 941510729  35 YYFNSSAATVAFILNDkNELLVCRRGKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEEAVYQFSLPNTYLYSG 114
Cdd:cd04681    1 YFHNVAAAVGVIIRNE-GEILFVRRAKEPGKGKLDLPGGFVDPGESAEEALRRELREELGLKIPKLRYLCSLPNTYLYKG 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 941510729 115 FLVHTLDQFFLCKVKDTSRI-KAMDDVAESFWLPLDEVNPEEFGLDSVREGVRRFL 169
Cdd:cd04681   80 ITYKTCDLFFTAELDEKPKLkKAEDEVAELEWLDLEEIEPEKLAFPSIRKAVERYI 135

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 941510729  42 ATVAFILNDKNELLVCRRGKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEEAVYQFSLPNTYLYSGFLVHTLd 121
Cdd:cd02883    2 AVGAVVFDDEGRVLLVRRSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEGRHVVVL- 80

                         90       100
                 ....*....|....*....|....*..
gi 941510729 122 qFFLCKVKDTSRIKAMDD-VAESFWLP 147
Cdd:cd02883   81 -VFLARVVGGEPPPLDDEeISEVRWVP 106

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941510729  44 VAFILNDKN-ELLVCRRGKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVE--EAVYQFSLPN----------TY 110
Cdd:cd18873    8 VIFGFDDGElKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETGLKDIylEQLGTFGDPDrdprgrvisvAY 87

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 941510729 111 LysgFLVHtldqfflckvKDTSRIKAMDDVAESFWLPLDEVNPE 154
Cdd:cd18873   88 L---ALVP----------EEDLAPKAGDDAAEARWFPVDELLPP 118

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941510729  40 SAATVAFILNDKNELLVCRRGKEPA-KGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEEAVYQFSLPntylYSGFLVH 118
Cdd:COG0494   13 RPAVVVVLLDDDGRVLLVRRYRYGVgPGLWEFPGGKIEPGESPEEAALRELREETGLTAEDLELLGELP----SPGYTDE 88

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 941510729 119 TLDQFFLCKVKDTSRIKAMDD--VAESFWLPLDEV 151
Cdd:COG0494   89 KVHVFLARGLGPGEEVGLDDEdeFIEVRWVPLDEA 123

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 941510729  45 AFILNDKNELLV---CRRGKEPAKgtldLSGGFIDMHETGEEGVAREVLEETGLQVE-EAV--------YQFSLPNTYly 112
Cdd:cd04670    7 GLVINENNEVLVvqeKYGGPGGWK----LPGGLVDPGEDIGEAAVREVFEETGIDTEfVSIlgfrhqhpGRFGKSDLY-- 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 941510729 113 sgFLvhtldqfFLCKVKDTSRIKAMDD-VAESFWLPLDE 150
Cdd:cd04670   81 --FV-------CRLRPLSDEEIKICPEeIAEAKWMPLEE 110

NADH pyrophosphatase; NADH pyrophosphatase, also known as NUDIX (nucleoside diphosphate linked moiety X)) motif 13/Nudt13, is thought to have NADH pyrophosphatase activity, be involved in NADH metabolic process and NADP catabolic process, catalyzing the cleavage of NADH into reduced nicotinamide mononucleotide (NMNH) and AMP, and located in mitochondrion. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity. Members of this family are also recognized by 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. A block of 8 conserved amino acids downstream of the NUDIX motif is thought to give NADH pyrophosphatase its specificity for NADH. NADH pyrophosphatase forms a dimer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941510729  47 ILNDKNELLVCRRGKEPaKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEEAVYQFSLPntYLYSGFLVHTldqfFLC 126
Cdd:cd03429    8 VTNGEDKILLARQPRWP-PGRYSLLAGFVEPGETLEEAVRREVKEEVGLRVKNVRYVGSQP--WPFPSSLMLG----FTA 80

                         90       100
                 ....*....|....*....|....*
gi 941510729 127 KVKDTSRIKAMDDVAESFWLPLDEV 151
Cdd:cd03429   81 EADSGEITVDDDELEDARWFSRDEL 105

NADH pyrophosphatase NudC, Nudix superfamily [Nucleotide transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941510729   8 KYCPKCGSPHFEVNNEKSKRCADCGFVYYFNSSAATVAFILnDKNELLVCR--RGKEPAKGTLdlsGGFIDMHETGEEGV 85
Cdd:COG2816  126 RFCGRCGAPTVVAAAGWARRCPACGAEHYPRTDPAVIVLVT-DGDRILLARqaRWPPGRYSLL---AGFVEPGETLEQAV 201

                         90       100
                 ....*....|....*....|..
gi 941510729  86 AREVLEETGLQVEEAVYQFSLP 107
Cdd:COG2816  202 RREVFEEVGVRVKNVRYVGSQP 223

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 941510729  52 NELLVCRRGKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEE----AVYQFSLPnTYLYSGFLVHTLdqFFLCK 127
Cdd:cd04686   12 DKLLLIRKTRGPYQGRYDLPGGSQEFGESLEDALKREFAEETGMTVTSydnlGVYDFFVP-WSDKELGDVHHI--GVFYD 88

                         90       100       110
                 ....*....|....*....|....*....|...
gi 941510729 128 VK-DTSRIK-----AMDDVAESFWLPLDEVNPE 154
Cdd:cd04686   89 VElLDNNISellqfEGQDSLGAVWIPLQDLTEL 121

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 941510729  41 AATVAFILNDKNELLVCRRGKepaKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEEavyqFSLPNTYlYSGFLVHTL 120
Cdd:cd04677   13 VGAAVIILNEQGRILLQKRTD---TGDWGLPGGAMELGESLEETARREVFEETGLTVEE----LELLGVY-SGKDLYYTY 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 941510729 121 ---DQFF----LCKVKDTSRIKAMDDvAESF---WLPLDEVnPEEF 156
Cdd:cd04677   85 pngDEVYnvtaVYLVRDVSGELKVDD-EESLelrFFSLDEL-PENI 128

NAD(+) diphosphatase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941510729   8 KYCPKCGSPHFEVNNEKSKRCADCGFVYYFNSSAATVAFIlNDKNELLVCR--RGKEPAKGTLdlsGGFIDMHETGEEGV 85
Cdd:PRK00241 100 RFCGYCGHPMHPSKTEWAMLCPHCRERYYPRIAPCIIVAV-RRGDEILLARhpRHRNGVYTVL---AGFVEVGETLEQCV 175

                         90
                 ....*....|..
gi 941510729  86 AREVLEETGLQV 97
Cdd:PRK00241 176 AREVMEESGIKV 187

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 941510729  43 TVAFILNDKNELLVCRRGKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGL 95
Cdd:cd04691    3 GVGGVVVKEGKVLLVKRAYGPGKGRWTLPGGFVEEGETLDEAIVREVLEETGI 55

nudix hydrolase

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 941510729  42 ATVAFILNDkNELLVCRRGKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVE 98
Cdd:PLN02325  11 AVVVFLLKG-NSVLLGRRRSSIGDSTFALPGGHLEFGESFEECAAREVKEETGLEIE 66

MutT pyrophosphohydrolase; The MutT pyrophosphohydrolase is a prototypical NUDIX hydrolase that catalyzes the hydrolysis of nucleoside and deoxynucleoside triphosphates (NTPs and dNTPs) by substitution at a beta-phosphorus to yield a nucleotide monophosphate (NMP) and inorganic pyrophosphate (PPi). This enzyme requires two divalent cations for activity; one coordinates the phosphoryl groups of the NTP/dNTP substrate, and the other coordinates to the enzyme. It also contains the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as metal binding and catalytic site. MutT pyrophosphohydrolase is important in preventing errors in DNA replication by hydrolyzing mutagenic nucleotides such as 8-oxo-dGTP (a product of oxidative damage), which can mispair with template adenine during DNA replication, to guanine nucleotides.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941510729  43 TVAFILNDkNELLVCRRGKEPAKGTL-DLSGGFIDMHETGEEGVAREVLEETGLQVEeaVYQFSLPNTYLYSGFLVHtLD 121
Cdd:cd03425    4 VAAIIVDD-GRVLIAQRPEGKHLAGLwEFPGGKVEPGETPEQALVRELREELGIEVE--VGEPLGTVEHDYPDFHVR-LH 79

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 941510729 122 qFFLCK-VKDTSRIKAMDDVAesfWLPLDEVNPEEF 156
Cdd:cd03425   80 -VYLCTlWSGEPQLLEHQELR---WVTPEELDDLDW 111

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 941510729  42 ATV-AFILNDKNELLVCRRGKepAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQ--------VEEAVY--QFSLPNTY 110
Cdd:cd18874    3 PTVgALIFNPDGKVLLVRSHK--WNDLYGIPGGKVEWGETLEEALKREVKEETGLDitdirfilVQESINseEFHKPAHF 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 941510729 111 LYsgflvhtLDqfFLCKVkDTSRIKAMDDVAESFWLPLDE 150
Cdd:cd18874   81 VF-------VD--YLART-DSSEVVLNEEAVEYLWVEPEE 110

8-oxo-DGDP phosphatase; 8-oxo-DGDP phosphatase (8DGDPP; EC 3.6.1.55), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 18/Nudt18; 2-hydroxy-DADP phosphatase; 7,8-dihydro-8-oxoguanine phosphatase, hydrolyzes 8-oxo-7,8-dihydroguanine (8-oxo-Gua)-containing deoxyribo- and ribonucleoside diphosphates to the monophosphates. 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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 941510729  43 TVAFILNDKNELLVCRRGKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVE 98
Cdd:cd04671    3 VAAVIINEQGEVLMIQEAKRSCRGKWYLPAGRVEPGESIVEAAKREVKEETGLKCE 58

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941510729  45 AFILNDKNELLVCRrgkePAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVE------EAVYQFSLPNTYLYsgflVH 118
Cdd:cd04684   20 AVIFNDEGKVLLVQ----TPNGGYFLPGGGIEPGETPEEALHREVLEETGWEIEigeflgNASRYFYSPDYDRY----YL 91

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 941510729 119 TLDQFFLC-KVKDTSriKAMDDVAESFWLPLDEVNpEEFGLDSVREGVRRFL 169
Cdd:cd04684   92 NIGYFYLAeLVRKVS--EPTEEDHELVWLPPEEAA-DLLKHEHHRWAVAKWL 140

nucleoside diphosphate-linked moiety X)) motif 17; Nucleoside diphosphate-linked moiety X)) motif 17 (EC 3.6.1.-) encoded by the NUDT17 gene on chromosome 1q21.1 and encodes an enzyme thought to hydrolyse some nucleoside diphosphate derivatives. 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 941510729  42 ATVAFILNDKNELLVCRRGKEPAK--GTLDLSGGFIDMHETGEEGVAREVLEETGLQVE-----------EAVY----QF 104
Cdd:cd04694    4 GVVVLIEDSDDRVLLTRRAKHMRTfpGVWVPPGGHVELGESLLEAGLRELQEETGLEVSdiqslsllglwESVYptllSI 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 941510729 105 SLPNTylysgflvHTLDQFFLCKVKDTSRIKAM-----DDVAESFWLPLDEVN 152
Cdd:cd04694   84 GLPKR--------HHIVVYYLVKLSESHENQEQlklqeDEVDAAVWLPKSLLA 128

8-oxo-dGTP diphosphatase MutT;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941510729  44 VAFILNDKNELLVCRRgkePAK----GTLDLSGGFIDMHETGEEGVAREVLEETGLQVEEAV------YQFSLPNTYLYS 113
Cdd:PRK10776   8 VGIIRNPNNEIFITRR---AADahmaGKWEFPGGKIEAGETPEQALIRELQEEVGITVQHATlfekleYEFPDRHITLWF 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 941510729 114 gFLVHTLDQFFLCKVKDTSRikamddvaesfWLPLDEVNPEEF 156
Cdd:PRK10776  85 -WLVESWEGEPWGKEGQPGR-----------WVSQVALNADEF 115

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 941510729  32 GFVYYFNSSAATVAFIlnDKNELLVCRRGKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEEA----VYQFSLP 107
Cdd:cd18884    1 GFVHWNNPIPVVAAIV--EHDGHIVLARNKAWPEGWYGLVTGFLEAGESPEEAVLREVKEELGLDGHEAkfigHYAFPER 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 941510729 108 NTyLYSGFlvhtldqfflcKVKDTSRIKAMDDVAESFWLPLDEVNPEEFG 157
Cdd:cd18884   79 NQ-LIIAY-----------HVRARGNVKLNEELDDYKIVPIDKLRPWPFG 116

ADP-ribose pyrophosphatase, UDP-glucose pyrophosphatase, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) ( NUDIX (Nucleoside diphosphate-linked moiety X)) motif 5; Nudt5) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 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. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941510729  67 TLDLSGGFIDMHETGEEGVAREVLEETGLQVEEAVYqfsLPNTYLYSGFLVHTLdQFFLCKVKDTSRIKAMDD--VAESF 144
Cdd:cd03424   30 LLELPAGKIDPGEDPEEAARRELEEETGYTAGDLEL---LGSFYPSPGFSDERI-HLFLAEDLTPVSEQALDEdeFIEVV 105

                 ....*..
gi 941510729 145 WLPLDEV 151
Cdd:cd03424  106 LVPLEEA 112

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 941510729  40 SAATVAFILNDKNELLVCRRGKEPA---KGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEE 99
Cdd:cd18882    1 HEVAIAILYDDRGKVLLQLRDDKPGipyPGYWGLFGGHLEPGETPEEAIRRELEEEIGYEPGE 63

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 941510729  44 VAFILNDKN-ELLVCRRGKEPAKGtLDLSGGFIDMHETGEEGVAREVLEETGLQVE-EAVYQFSlpntYLYSGFLVHTLD 121
Cdd:cd04663    4 CAYVTRGRNrELLVFEHPDFPEAG-LQVPKGTVEPGESPEEAALRELAEETGLTGArVVVDLGS----HDEGFEELHQRW 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 941510729 122 QFFLC---KVKDTSRIKAMDDVAES------FWLPLDEVNP---EEFG 157
Cdd:cd04663   79 FFHLClagEPPERWEHHETDDGEGGglrfefFWVPLAAAPPrlaAGFG 126

CDP-Choline Pyrophosphatase and similar proteins; Members include: CDP-Choline Pyrophosphatase, ADP-ribose pyrophosphatase, and UDP-X diphosphatase. CDP-choline pyrophosphatase catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. ADP-ribose pyrophosphatase catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. UDP-X diphosphatase hydrolyzes UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-alanine. 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 941510729  45 AFILNDKNELLVcrrgKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEE----AVYQfslPNTYLYSGFLVHTL 120
Cdd:cd04672    7 AAVFKDGKILLV----REKSDGRWTLPGGWADVGLSPAENAVKEVREESGYEVRArkllAVFD---RNKGGHPPSPFHVY 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 941510729 121 DQFFLCKVKDTSRIKAMdDVAESFWLPLDEVNP 153
Cdd:cd04672   80 KLFFLCELIGGEAQTSI-ETSEVGFFALDDLPP 111

diadenosine tetraphosphate; Diadenosine tetraphosphate (Ap4A; EC 3.6.1.17), also called NUDIX (nucleoside diphosphate-linked moiety X)) motif 2/Nudt2, is a member of the NUDIX hydrolase superfamily. Ap4A hydrolases are well represented in a variety of prokaryotic and eukaryotic organisms. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one subfamily and fungi/animals/archaea enzymes, represented by this subfamily, fall into another. Bacterial enzymes are found in both subfamilies. Ap4A is a potential by-product of aminoacyl tRNA synthesis, and accumulation of Ap4A has been implicated in a range of biological events, such as DNA replication, cellular differentiation, heat shock, metabolic stress, and apoptosis. Ap4A hydrolase cleaves Ap4A asymmetrically into ATP and AMP. It is important in the invasive properties of bacteria and thus presents a potential target for inhibition of such invasive bacteria. Besides the signature NUDIX motif (G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val) that functions as a metal binding and catalytic site, and a required divalent cation, Ap4A hydrolase is structurally similar to the other members of the NUDIX hydrolase superfamily with some degree of variation. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 941510729  23 EKSkrcadCGFVyyfnssaatVAFILNDKNE-LLVCRRgkepAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEEAV 101
Cdd:cd03428    2 EKS-----AGAI---------IYRRDNGEIEfLLLQHS----YGGHWDFPKGHVEPGESELETALRETKEETGLTVDDLP 63

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 941510729 102 YQFSLPNTYLYSGFlVHTLDQFFLCKVKDTSRIKAMDDVAESFWLPLDE 150
Cdd:cd03428   64 PGFRETLTYSFKEG-VEKTVVYFLAELTPDVEVKLSEEHQDYKWLPYEE 111

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 941510729  41 AATVAFILNDKNELLVCRRgkePAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVE 98
Cdd:cd18876    1 AAAGALFTDAAGRVLLVKP---TYKDGWELPGGVVEAGESPLQAARREVREELGLDVP 55

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 941510729  47 ILNDKNELLVCRR-GKEPAKGTLDLSGGFIDMHETGEEGVAREVLEETGLQVEEAVYQFslpntylysgflVHT------ 119
Cdd:cd04683    6 LLVRGDEVLLLRRaNTGYDDGWWHLPAGHVEAGETVRAAAVREAKEELGVEIDPEDLRL------------VHTmhrrsd 73

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 941510729 120 -----LDQFFLC-KVKDTSRIKAMDDVAESFWLPLDEVnPEEFgLDSVREGVRR 167
Cdd:cd04683   74 ggrerIDFFFRAtRWSGEPRNREPDKCAELRWFPLDAL-PENT-VPYVRAALEA 125