NCBI Conserved Domain Search

GDP-mannose mannosyl hydrolase;

Pssm-ID: 237966 [Multi-domain] Cd Length: 159 Bit Score: 331.33 E-value: 1.36e-118

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398   1 MFLSQEDFATVVRSTPLISIDLIVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLPMAAGQ 80
Cdd:PRK15434   1 MFLRQEDFATVVRSTPLISLDFIVENSRGEFLLGKRTNRPAQGYWFVPGGRVQKDETLEAAFERLTMAELGLRLPITAGQ 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 504697398  81 FYGVWQHFYDDNFSGTGFTTHYIVLGFRLKVTQADLRLPDAQHDDYRWLAPEPLLASENVHDNSRAYFLADRQAEVPGI 159
Cdd:PRK15434  81 FYGVWQHFYDDNFSGTDFTTHYVVLGFRLRVAEEDLLLPDEQHDDYRWLTPDALLASDNVHANSRAYFLAEKRAGVPGL 159

GDP-mannose glycosyl hydrolase; GDP-mannose glycosyl hydrolase, also known as GDP-mannose mannosyl hydrolase/GDPMH, is a member of the NUDIX hydrolase superfamily. This class of enzymes is unique from other members of the superfamily in two aspects. First, it contains a modified NUDIX signature sequence. The slight changes to the conserved sequence motif, GX5EX7REUXEEXGU, where U = I, L or V), are believed to contribute to the removal of all magnesium binding sites but one, retaining only the metal site that coordinates the pyrophosphate of the substrate. Secondly, it is not a pyrophosphatase that substitutes at a phosphorus; instead, it hydrolyzes nucleotide sugars such as GDP-mannose to GDP and mannose, cleaving the phosphoglycosyl bond by substituting at a carbon position. GDP-mannose provides mannosyl components for cell wall synthesis and is required for the synthesis of other glycosyl donors (such as GDP-fucose and colitose) for the cell wall. The importance of GDP-sugar hydrolase activities is thus closely related to the regulation of cell wall biosynthesis. Enzymes in this family are believed to regulate the concentration of GDP-mannose and GDP-glucose in the bacterial cell wall.

Pssm-ID: 467536 [Multi-domain] Cd Length: 146 Bit Score: 254.47 E-value: 1.94e-88

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398   3 LSQEDFATVVRSTPLISIDLIVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLPMAAGQFY 82
Cdd:cd03430    1 LPEEDFKTVVENTPLVSIDLIIRNEDGEILLGKRNNRPAQGYWFVPGGRILKNETLDDAFKRIAREELGLEVTINAAEFL 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 504697398  83 GVWQHFYDDNFSGTGFTTHYIVLGFRLKVTQADLRLPDAQHDDYRWLAPEPLLASENVHDNSRAYF 148
Cdd:cd03430   81 GVYEHFYDDNFSGEDFSTHYVVLAYRLKLDEGLLLLPDDQHDEYRWFTIDELLANDDVHPYTKAYF 146

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 79.64 E-value: 8.92e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  14 STPLISIDLIVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLpmAAGQFYGVWQHFYddnf 93
Cdd:COG1051    3 KVPKVAVDAVIFRKDGRVLLVRRADEPGKGLWALPGGKVEPGETPEEAALRELREETGLEV--EVLELLGVFDHPD---- 76

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 504697398  94 sgtgfTTHYIVLGFRLKVTQADLRLPDaQHDDYRWLAPE 132
Cdd:COG1051   77 -----RGHVVSVAFLAEVLSGEPRADD-EIDEARWFPLD 109

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 76.75 E-value: 1.24e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398   15 TPLISIDLIVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLPMaaGQFYGVWQHFYDDNFS 94
Cdd:pfam00293   1 KRRVAVGVVLLNEKGRVLLVRRSKKPFPGWWSLPGGKVEPGETPEEAARRELEEETGLEPEL--LELLGSLHYLAPFDGR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 504697398   95 GTgfTTHYIVLGFRLKVTQADLRLPDAQHDDYRWLAPEPLLASENVHDNSRAY 147
Cdd:pfam00293  79 FP--DEHEILYVFLAEVEGELEPDPDGEVEEVRWVPLEELLLLKLAPGDRKLL 129

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.

Pssm-ID: 467528 [Multi-domain] Cd Length: 106 Bit Score: 65.12 E-value: 2.14e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  23 IVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLpmAAGQFYGVWQHFYDDNfsgtgfTTHY 102
Cdd:cd02883    6 VVFDDEGRVLLVRRSDGPGPGGWELPGGGVEPGETPEEAAVREVREETGLDV--EVLRLLGVYEFPDPDE------GRHV 77

                         90       100
                 ....*....|....*....|....*...
gi 504697398 103 IVLGFRLKVTQADLRLPDAQ-HDDYRWL 129
Cdd:cd02883   78 VVLVFLARVVGGEPPPLDDEeISEVRWV 105

ADP-ribose pyrophosphatase; 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.

Pssm-ID: 467557 [Multi-domain] Cd Length: 128 Bit Score: 53.67 E-value: 8.34e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  29 GEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLpmAAGQFYGVWQHFYDDNFSGTGFttHYIVLGFR 108
Cdd:cd04673   12 GRVLLVRRGNPPDAGLWSFPGGKVELGETLEDAALRELREETGLEA--EVVGLLTVVDVIERDEAGRVRF--HYVILDFL 87

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 504697398 109 LKVTQADLRL-PDAqhDDYRWLAPEPLLAsENVHDNSRA 146
Cdd:cd04673   88 AEWVSGEPVAgDDA--LDARWFSLEELDG-LPLTPGTRD 123

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.

Pssm-ID: 467576 [Multi-domain] Cd Length: 135 Bit Score: 52.68 E-value: 2.25e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  23 IVENERGEFLLGKRtNRPAQGF---WFVPGGRVQKDETLHDAFERLTLAELGLQLPM-AAGQFYGVWQHFYDDNFSGTGF 98
Cdd:cd04694    8 LIEDSDDRVLLTRR-AKHMRTFpgvWVPPGGHVELGESLLEAGLRELQEETGLEVSDiQSLSLLGLWESVYPTLLSIGLP 86

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 504697398  99 TTHYIVLGFRLKV-----TQADLRLPDAQHDDYRWLAPEPLLASENVHD 142
Cdd:cd04694   87 KRHHIVVYYLVKLsesheNQEQLKLQEDEVDAAVWLPKSLLAKLLEAED 135

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.

Pssm-ID: 467579 [Multi-domain] Cd Length: 118 Bit Score: 50.31 E-value: 9.58e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  18 ISIDLIVENErGEFLLGKRtNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQlpMAAGQFYGVWQHFYDDnfsgtg 97
Cdd:cd04699    3 VSVKGVIFDN-GRVLLLRR-SRAGAGEWELPGGRLEPGESPEEALKREVKEETGLD--VSVGELLDTWTFELDP------ 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 504697398  98 fTTHYIVLGFRLKVTQADLRLPDaQHDDYRWLAPEPLLASE 138
Cdd:cd04699   73 -DKGVFIVTYLCRLVGGEVTLSD-EHEEYEWVTPEELAELE 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.

Pssm-ID: 467564 [Multi-domain] Cd Length: 135 Bit Score: 49.88 E-value: 2.19e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 504697398  23 IVENErGEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLP 75
Cdd:cd04681   12 IIRNE-GEILFVRRAKEPGKGKLDLPGGFVDPGESAEEALRRELREELGLKIP 63

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.

Pssm-ID: 467562 [Multi-domain] Cd Length: 126 Bit Score: 49.61 E-value: 2.53e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  28 RGEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLpmAAGQFYGVWQHFYDDNfsgtgfTTHYIVLGF 107
Cdd:cd04679   12 DGRLLLVLRLRAPEAGHWGLPGGKVDWLETVEDAVRREILEELGLEI--ELTRLLCVVDQIDAAD------GEHWVAPVY 83

                         90       100       110
                 ....*....|....*....|....*....|...
gi 504697398 108 RLKVTQADLRL--PDAqHDDYRWLA----PEPL 134
Cdd:cd04679   84 LAEIFSGEPRLmePEK-HGGIGWFAldalPQPL 115

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.

Pssm-ID: 467573 [Multi-domain] Cd Length: 122 Bit Score: 48.45 E-value: 6.07e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  23 IVENErGEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQ---LPMAAGQFyGVWQHFYDDNfsgtgft 99
Cdd:cd04691    7 VVVKE-GKVLLVKRAYGPGKGRWTLPGGFVEEGETLDEAIVREVLEETGIDakpVGIIGVRS-GVIRDGKSDN------- 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 504697398 100 thYIVlgFRLKVTQADLRLPDAQHDDYRWLAPEPLLASENVHDNSRA 146
Cdd:cd04691   78 --YVV--FLLEYVGGEPKPDERENSEAGFLTLEEALANEDIADMSRE 120

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.

Pssm-ID: 467531 [Multi-domain] Cd Length: 123 Bit Score: 48.22 E-value: 8.40e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  23 IVENErGEFLLGKRT-NRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLpmAAGQFYGVWQHFYDDNfsgtgfttH 101
Cdd:cd03425    7 IIVDD-GRVLIAQRPeGKHLAGLWEFPGGKVEPGETPEQALVRELREELGIEV--EVGEPLGTVEHDYPDF--------H 75

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 504697398 102 YIVLGFRLKVTQADLRLPDaqHDDYRWLAPEPLLA 136
Cdd:cd03425   76 VRLHVYLCTLWSGEPQLLE--HQELRWVTPEELDD 108

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

Pssm-ID: 440260 [Multi-domain] Cd Length: 143 Bit Score: 48.11 E-value: 1.25e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  22 LIVENERGEFLLGKRTNRPAQ-GFWFVPGGRVQKDETLHDAFERLTLAELGLQLpmaagqfyGVWQHFYD-DNFSGTGFT 99
Cdd:COG0494   18 VVLLDDDGRVLLVRRYRYGVGpGLWEFPGGKIEPGESPEEAALRELREETGLTA--------EDLELLGElPSPGYTDEK 89

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 504697398 100 THYIVLGFRLKVTQADLRLPDAqHDDYRWLAPEPLLA 136
Cdd:COG0494   90 VHVFLARGLGPGEEVGLDDEDE-FIEVRWVPLDEALA 125

MutT homolog 2; MutT Homolog 2 (MTH2; EC 3.6.1.9), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 15/Nudt15, may catalyze the hydrolysis of nucleoside diphosphates, triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP, and prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP. MTH2 may also play a role in DNA synthesis and cell cycle progression by stabilizing PCNA. 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.

Pssm-ID: 467561 [Multi-domain] Cd Length: 128 Bit Score: 47.17 E-value: 1.72e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  16 PLISIDLIVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLPmaAGQFYGVWQ-HFYDDNFs 94
Cdd:cd04678    1 PRVGVGVIVLNDDGKVLLGRRKGSHGAGTWALPGGHLEFGESFEECAAREVLEETGLEIR--NVRFLTVTNdVFEEEGK- 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 504697398  95 gtgfttHYIVLGFRLKV---TQADLRLPDaQHDDYRWLAPEPLLASENVHDNSRAYF 148
Cdd:cd04678   78 ------HYVTIFVLAEVddgEPEENMEPD-KCEGWEWFSWDELPPLRPLFLPLANLL 127

dihydroneopterin hydrolase; DHNTP pyrophosphatase (DHNTPase) catalyzes the hydrolysis of dihydroneopterin triphosphate (DHNTP) to dihydroneopterin monophosphate (DHNMP) and pyrophosphate,the second step in the pterin branch of the folate synthesis pathway in bacteria. 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.

Pssm-ID: 467549 [Multi-domain] Cd Length: 132 Bit Score: 47.24 E-value: 2.03e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  22 LIVENERGEFLLGKRTNRPaqGFW-FVpGGRVQKDETLHDAFERLTLAELGLQLpmaAGQFYGVWQH--FYDDNFSGTGF 98
Cdd:cd04664    7 IYRKDEEGEVLLLKRTDDG--GFWqSV-TGGIEDGETPWQAALRELKEETGLDP---LELQLIDLNVsnFYEIFDDWRPG 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 504697398  99 TTHYIVLGFRLKVT-QADLRLpDAQHDDYRWLAPE 132
Cdd:cd04664   81 VTVNTEHVFAVEVPeEQPIRL-SPEHTDYRWLPYE 114

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.

Pssm-ID: 467585 [Multi-domain] Cd Length: 132 Bit Score: 46.00 E-value: 5.69e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 504697398  16 PLISIDLIV---ENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLP 75
Cdd:cd18873    1 PSVTVDCVIfgfDDGELKVLLIKRKNEPFKGGWALPGGFVREDETLEDAARRELREETGLKDI 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.

Pssm-ID: 467593 [Multi-domain] Cd Length: 130 Bit Score: 45.71 E-value: 7.06e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  26 NERGEFLLGKRTNRPA---QGFWFVPGGRVQKDETLHDAFERLTLAELGLQLPMAAgqfygvWQHFYDDNFSGTGfTTHY 102
Cdd:cd18882   10 DDRGKVLLQLRDDKPGipyPGYWGLFGGHLEPGETPEEAIRRELEEEIGYEPGEFR------FFLLYTEDDGEDR-IRHV 82

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 504697398 103 IVlgFRLKVTQADLRLPDAQhdDYRWLAPEPLLASE 138
Cdd:cd18882   83 FH--APLDVDLSDLVLNEGQ--ALRLFSPEEILQGP 114

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.

Pssm-ID: 467588 [Multi-domain] Cd Length: 121 Bit Score: 43.73 E-value: 3.79e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  22 LIVENERGEFLLGKRTNRPaqgFWFVPGGRVQKDETLHDAFERLTLAELGLQLPmaAGQFYGVwqhFYDDNFSGTGFTTH 101
Cdd:cd18876    5 ALFTDAAGRVLLVKPTYKD---GWELPGGVVEAGESPLQAARREVREELGLDVP--VGRLLAV---DWVPPAGGGDDAVL 76

                         90       100       110
                 ....*....|....*....|....*....|..
gi 504697398 102 YIVLGFRLKVTQAD-LRLPDAQHDDYRWLAPE 132
Cdd:cd18876   77 FVFDGGVLTPEQAAaIRLQDEELSAYRFVTPE 108

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.

Pssm-ID: 467575 [Multi-domain] Cd Length: 157 Bit Score: 44.05 E-value: 4.29e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  10 TVVRSTPL------ISIDLIVENERGEFLLGKR--TNRPAQGFW-FVPGGRVQKDETLHDAFERLTLAELGLQLPMAAGQ 80
Cdd:cd04693   16 THRRGEPLpegeyhLVVHVWIFNSDGEILIQQRspDKKGFPGMWeASTGGSVLAGETSLEAAIRELKEELGIDLDADELR 95

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 504697398  81 FYGvWQHFYDdnfsgtGFTTHYIvlgFRLKVTQADLRLpdaQHD---DYRWLAPEPLLA 136
Cdd:cd04693   96 PIL-TIRFDN------GFDDIYL---FRKDVDIEDLTL---QKEevqDVKWVTLEEILE 141

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.

Pssm-ID: 467586 [Multi-domain] Cd Length: 125 Bit Score: 43.04 E-value: 6.18e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  16 PLISIDLIVENERGEFLLGKRTNrpAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLPMAagQFYGVWQHFYDDNFSG 95
Cdd:cd18874    1 PEPTVGALIFNPDGKVLLVRSHK--WNDLYGIPGGKVEWGETLEEALKREVKEETGLDITDI--RFILVQESINSEEFHK 76

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 504697398  96 TGfttHYIVLGFRLKVTQADLRLPDaQHDDYRWLAPE 132
Cdd:cd18874   77 PA---HFVFVDYLARTDSSEVVLNE-EAVEYLWVEPE 109

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.

Pssm-ID: 467555 [Multi-domain] Cd Length: 130 Bit Score: 43.07 E-value: 7.82e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 504697398  23 IVENERGEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQL 74
Cdd:cd04671    6 VIINEQGEVLMIQEAKRSCRGKWYLPAGRVEPGESIVEAAKREVKEETGLKC 57

Nudix family hydrolase;

Pssm-ID: 236361 [Multi-domain] Cd Length: 312 Bit Score: 42.55 E-value: 3.28e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 504697398  23 IVENERGEFLLGKRT-NRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQ 73
Cdd:PRK08999  11 VIRDADGRILLARRPeGKHQGGLWEFPGGKVEPGETVEQALARELQEELGIE 62

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.

Pssm-ID: 467554 [Multi-domain] Cd Length: 131 Bit Score: 40.21 E-value: 7.59e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  23 IVENERGEFLLGKRTNRPAqGFWFVPGGRVQKDETLHDAFERLTLAELGLQLpmaagQFYGV--WQHFYDDNFsgtGFTT 100
Cdd:cd04670    8 LVINENNEVLVVQEKYGGP-GGWKLPGGLVDPGEDIGEAAVREVFEETGIDT-----EFVSIlgFRHQHPGRF---GKSD 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 504697398 101 HYIVlgFRLK-VTQADLRLPDAQHDDYRWLAPEPLLASENVHDNSRA 146
Cdd:cd04670   79 LYFV--CRLRpLSDEEIKICPEEIAEAKWMPLEEYLKQPNVSQINKL 123

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 41.53 E-value: 7.81e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 504697398  29 GEFLLGKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLPMAAGQFYGVWQHFYDD 91
Cdd:PRK05379 214 GHVLLVRRRAEPGKGLWALPGGFLEQDETLLDACLRELREETGLKLPEPVLRGSIRDQQVFDH 276

NUDIX hydrolase subfamily; Nucleoside triphosphatase NudI catalyzes the hydrolysis of nucleoside triphosphates, with a preference for pyrimidine deoxynucleoside triphosphates (dUTP, dTTP and dCTP). It is a members of the NUDIX hydrolase superfamily which 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.

Pssm-ID: 467577 [Multi-domain] Cd Length: 134 Bit Score: 40.30 E-value: 8.36e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  23 IVENErGEFLLGKR-TNR---PAQgfWFVPGGRVQKDETLHDAFERLTLAELGLQLPMAAGQfygVWQhFYDDNF----- 93
Cdd:cd04696    8 LIENE-GCYLLCKMaDDRgvfPGQ--WALSGGGVEPGERIEEALRREIREELGEQLILSDIT---PWT-FRDDIRiktyp 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 504697398  94 SGTGFTTHYIVLGFRLKVTQADLRLPDaQHDDYRWLAPEPL 134
Cdd:cd04696   81 DGRQEEIYMIYLIFDCVSANRDVCIND-EFQDYAWVKPADL 120

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.

Pssm-ID: 467559 [Multi-domain] Cd Length: 144 Bit Score: 38.92 E-value: 2.66e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  19 SIDLIVENERGEFLLGKRTNrpaQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLPMAagQFYGVwqhfyddnFSGTGF 98
Cdd:cd04676   19 SVAAVILNEDGRILLQRKGG---LGLWSLPAGAIEPGEHPAEAVIREVREETGLLVKPT--RLLGV--------FGGKEF 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 504697398  99 --------TTHYIVLGFRLKVTQADLRLPDAQHDDYRWLAPE--PLLA 136
Cdd:cd04676   86 rytypngdQVEYTVIAFKCVVTGGTLNAIDGETSELRYFSRTqmPTLA 133

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.

Pssm-ID: 467534 [Multi-domain] Cd Length: 132 Bit Score: 38.69 E-value: 3.11e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  25 ENERGEFLLGKRtnrPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQlpmaagqfygvwQHFYDDNFSgtgFTTHYIV 104
Cdd:cd03428   13 DNGEIEFLLLQH---SYGGHWDFPKGHVEPGESELETALRETKEETGLT------------VDDLPPGFR---ETLTYSF 74

                         90       100       110
                 ....*....|....*....|....*....|....
gi 504697398 105 LGFRLK-VT--------QADLRLpDAQHDDYRWL 129
Cdd:cd03428   75 KEGVEKtVVyflaeltpDVEVKL-SEEHQDYKWL 107

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.

Pssm-ID: 467563 [Multi-domain] Cd Length: 121 Bit Score: 37.23 E-value: 9.30e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  23 IVENERGEFLLGKRTNRPaqgFWFVPGGRVQKDETLHDAFERLTLAELGLQLPMAAgQFYGVWQHFYDDNFSGTGFtthY 102
Cdd:cd04680    6 IVLDDAGRVLLVRHTYVP---GWYLPGGGVDKGETAEEAARRELREEAGVVLTGPP-RLFGVYFNRRVSPRDHVAL---Y 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 504697398 103 IVLGFRlkvtQADLRLPDAQHDDYRWLAPEPL 134
Cdd:cd04680   79 RVREFE----QTEPPEPNGEIAEAGFFALDAL 106

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.

Pssm-ID: 467560 [Multi-domain] Cd Length: 137 Bit Score: 36.34 E-value: 2.37e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  23 IVENERGEFLLGKRTNrpaQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLpmAAGQFYGVwqhfyddnFSGTGFTTHY 102
Cdd:cd04677   18 IILNEQGRILLQKRTD---TGDWGLPGGAMELGESLEETARREVFEETGLTV--EELELLGV--------YSGKDLYYTY 84

NUDIX domain;

Pssm-ID: 464330 [Multi-domain] Cd Length: 114 Bit Score: 35.75 E-value: 2.73e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398   22 LIVENERGEFLLGKRtnrPA----QGFWFVPGGRVQKDETLHDAFERltLAELGLQLPMAAGqfyGVWQHFYddnfsgtg 97
Cdd:pfam14815   3 LVIRNGDGRVLLRKR---PEkgllGGLWEFPGGKVEPGETLEEALAR--LEELGIEVEVLEP---GTVKHVF-------- 66

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 504697398   98 ftTHYIVlgfRLKV-TQADLRLPDAQHDDYRWLAPE 132
Cdd:pfam14815  67 --THFRL---TLHVyLVREVEGEEEPQQELRWVTPE 97

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.

Pssm-ID: 467542 [Multi-domain] Cd Length: 130 Bit Score: 35.70 E-value: 3.30e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  22 LIVENERGEFLLgkrTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQ---LPMAAGQFYGVWQHFYDDNFSGTGf 98
Cdd:cd03674    7 FVVNPDRGKVLL---VHHRKLGRWLQPGGHVEPDEDPLEAALREAREETGLDvelLSPLSPDPLDIDVHPIPANPGEPA- 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 504697398  99 TTHY-IVLGFRLKvTQADLRLPDaQHDDYRWLAPEpLLASENVHDNSRA 146
Cdd:cd03674   83 HLHLdVRYLAVAD-GDEALRKSD-ESSDVRWFPLD-ELEELSMDPNLRK 128

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.

Pssm-ID: 467568 [Multi-domain] Cd Length: 138 Bit Score: 35.63 E-value: 3.77e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  22 LIVENERGEFLL--GKRTNRPAQGFWFVPGGRVQKDETLHDAFERLTLAELGLQLPMAA--GQfygVWQHfyDDNFSGTG 97
Cdd:cd04685    5 VLLLDPDGRVLLfrFHDPDDPGRSWWFTPGGGVEPGESPEQAAVRELREETGLRLEPDDlgGP---VWRR--RAVFDFSG 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 504697398  98 FTTHYIVLGFRLKVTQADL---RLPDAQ---HDDYRWLAPEPLLASE 138
Cdd:cd04685   80 ETVRQDERFFLVRVPAFEVdtaGWTDLEravIDGHRWWSLAELAATG 126

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.

Pssm-ID: 467591 [Multi-domain] Cd Length: 126 Bit Score: 35.58 E-value: 3.80e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 504697398  22 LIVENERgeFLLGKrtNRPAQG-FWFVPGGRVQKDETLHDAFERLTLAELGL 72
Cdd:cd18880    7 IIIEDGK--LLLVK--HRDEGGiFYILPGGGQEHGETLPEALKRECLEETGL 54

diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 and similar proteins; Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 (DIPP2), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 4; Nudt4, and other proteins including DIPP1/Nudt3, DIPP3a;APS2/Nudt10 and DIPP3beta;APS1/Nudt11. DIPP regulates the turnover of diphosphoinositol polyphosphates. The turnover of these high-energy diphosphoinositol polyphosphates represents a molecular switching activity with important regulatory consequences. Molecular switching by diphosphoinositol polyphosphates may contribute to regulating intracellular trafficking. Several alternatively spliced transcript variants have been described, but the full-length nature of some variants has not been determined. Isoforms DIPP2alpha and DIPP2beta are distinguishable from each other solely by DIPP2beta possessing one additional amino acid due to intron boundary skidding in alternate splicing. 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.

Pssm-ID: 467551 [Multi-domain] Cd Length: 128 Bit Score: 35.20 E-value: 4.99e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  24 VENERGEFLL--GKRTNRpaqgfWFVPGGRVQKDETLHDAFERLTLAELGL---QLPMAAGQfygvwqhfYDDNFSGTGF 98
Cdd:cd04666   10 ITKGELEVLLitSRKTGR-----WILPKGGPEKGETPAEAAAREAWEEAGVrgkVLKRPLGV--------YRYRKRLKGR 76

                         90       100       110
                 ....*....|....*....|....*....|....
gi 504697398  99 TTHYIVLGFRLKVTQADLRLPDAQHDDYRWLAPE 132
Cdd:cd04666   77 GLPCRVHVFPLEVTEELDDWPEKHERKRRWFSPE 110

nucleoside triphosphatase NudI; Provisional

Pssm-ID: 185369 [Multi-domain] Cd Length: 141 Bit Score: 34.72 E-value: 7.44e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504697398  23 IVENErGEFLLGKR-TNR---PAQgfWFVPGGRVQKDETLHDAFERLTLAELGLQLPMAAgqfYGVWQhFYDD-----NF 93
Cdd:PRK15472  10 LIQND-GAYLLCKMaDDRgvfPGQ--WALSGGGVEPGERIEEALRREIREELGEQLLLTE---ITPWT-FRDDirtktYA 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 504697398  94 SGTGFTTHYIVLGFRLKVTQADLRLPDaQHDDYRWLAPEPL 134
Cdd:PRK15472  83 DGRKEEIYMIYLIFDCVSANRDVKINE-EFQDYAWVKPEDL 122