NCBI Conserved Domain Search

Uncharacterized conserved protein [Function unknown];

Pssm-ID: 443287 [Multi-domain] Cd Length: 170 Bit Score: 177.67 E-value: 1.86e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  52 ALPGGFIDMqkDDSTHATALRKLTEKTGVRPSWLEQLETFSGPDRDPRGWSLTTAWFALIAwvDCQPHIASVSDAQWVPV 131
Cdd:COG4111    1 ALPGGFVRE--HESLEDAARRWLAEQTGLELGYLEQLYTFGDPDRDPRGRVISVAYLALVR--EEELRADDADDAAWFPV 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145 132 AELDaiELAFDHQTIIEAALRRLRQKTMYSLLPVYCLPECFTLSQLQEATEIILGQPIQRKSLIRRFEASGMFEETGESV 211
Cdd:COG4111   77 DELP--PLAFDHRRILATALERLRAKLEYTPIGFELLPEKFTLSELQRLYEAILGRKLDKRNFRRKILSLGLLEETGEKQ 154

                        170
                 ....*....|....*.
gi 490521145 212 ATGA-RKARLWRRKPD 226
Cdd:COG4111  155 TGGAgRPAKLYRFDKE 170

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: 160.79 E-value: 1.92e-50

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  19 PLVTVDSVLFTLHDQALCVLLVQRARQPQQGRWALPGGFIDmqKDDSTHATALRKLTEKTGVRPSWLEQLETFSGPDRDP 98
Cdd:cd18873    1 PSVTVDCVIFGFDDGELKVLLIKRKNEPFKGGWALPGGFVR--EDETLEDAARRELREETGLKDIYLEQLGTFGDPDRDP 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 490521145  99 RGWSLTTAWFALIAWVDCQPHIAS-VSDAQWVPVAELdAIELAFDHQTIIEAAL 151
Cdd:cd18873   79 RGRVISVAYLALVPEEDLAPKAGDdAAEARWFPVDEL-LPPLAFDHAEIIADAL 131

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

Pssm-ID: 440671 [Multi-domain] Cd Length: 125 Bit Score: 89.27 E-value: 1.05e-22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  19 PLVTVDSVLFtlhDQALCVLLVQRARQPQQGRWALPGGFIDmqKDDSTHATALRKLTEKTGVRPSWLEQLETFSGPDrdp 98
Cdd:COG1051    5 PKVAVDAVIF---RKDGRVLLVRRADEPGKGLWALPGGKVE--PGETPEEAALRELREETGLEVEVLELLGVFDHPD--- 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 490521145  99 RGWSLTTAWFALIawVDCQPHIAS-VSDAQWVPVAELDAIELAFDHQTIIE 148
Cdd:COG1051   77 RGHVVSVAFLAEV--LSGEPRADDeIDEARWFPLDELPELAFTPADHEILE 125

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

Pssm-ID: 235436 [Multi-domain] Cd Length: 340 Bit Score: 81.60 E-value: 3.94e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145   3 TEAEYLETY----DPARFPSPLVTVDSVlftlHDQALCVLLVQRARQPQQGRWALPGGFIDmqKDDSTHATALRKLTEKT 78
Cdd:PRK05379 182 AEADFIEQYrkawAAAPYPPTFVTVDAV----VVQSGHVLLVRRRAEPGKGLWALPGGFLE--QDETLLDACLRELREET 255

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  79 G-------VRPSWLEQlETFSGPDRDPRGWSLTTAW-FALIAWVdcQPHIASVSDA---QWVPVAELDAIELAF--DHQT 145
Cdd:PRK05379 256 GlklpepvLRGSIRDQ-QVFDHPGRSLRGRTITHAFlFEFPAGE--LPRVKGGDDAdkaRWVPLAELLAMRDRMfeDHFQ 332


                 ...
gi 490521145 146 IIE 148
Cdd:PRK05379 333 IIT 335

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: 68.31 E-value: 1.15e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  37 VLLVQRARQPQQGRWALPGGFIDMqkDDSTHATALRKLTEKTGVRPSWLEQLETFSGPDRDPRGwsLTTAWFALIA---- 112
Cdd:cd04673   14 VLLVRRGNPPDAGLWSFPGGKVEL--GETLEDAALRELREETGLEAEVVGLLTVVDVIERDEAG--RVRFHYVILDflae 89

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 490521145 113 WVDCQPHIAS-VSDAQWVPVAELDAIELAFDHQTIIEAA 150
Cdd:cd04673   90 WVSGEPVAGDdALDARWFSLEELDGLPLTPGTRDVLERA 128

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: 62.74 E-value: 1.90e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  37 VLLVQRARQP-QQGRWALPGGFIDmqKDDSTHATALRKLTEKTGVRPSWLEQLETFSGpdrdPRGWSLTTAWF-ALIAWV 114
Cdd:COG0494   27 VLLVRRYRYGvGPGLWEFPGGKIE--PGESPEEAALRELREETGLTAEDLELLGELPS----PGYTDEKVHVFlARGLGP 100

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 490521145 115 DCQPHIAS---VSDAQWVPVAELDAIELAFDHQTIIEAALRRL 154
Cdd:COG0494  101 GEEVGLDDedeFIEVRWVPLDEALALVTAGEIAKTLAALARLL 143

NUDIX domain;

Pssm-ID: 395229 [Multi-domain] Cd Length: 132 Bit Score: 61.73 E-value: 3.77e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145   25 SVLFTLHDQALCVLLVQRARQPQQGRWALPGGFIDMqkDDSTHATALRKLTEKTGVRPSWLEQLETFSgPDRDPRGWSLT 104
Cdd:pfam00293   5 AVGVVLLNEKGRVLLVRRSKKPFPGWWSLPGGKVEP--GETPEEAARRELEEETGLEPELLELLGSLH-YLAPFDGRFPD 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 490521145  105 TAWFALIAWVDCQPHIAS-----VSDAQWVPVAELDAIELAFDHQTIIEA 149
Cdd:pfam00293  82 EHEILYVFLAEVEGELEPdpdgeVEEVRWVPLEELLLLKLAPGDRKLLPW 131

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: 61.05 E-value: 7.53e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  37 VLLVQRARQPQQGRWALPGGFIDMqkDDSTHATALRKLTEKTGVRPSWLEQLetFSGPDRDP-RGWSLTTAWFALIAWVD 115
Cdd:cd04681   19 ILFVRRAKEPGKGKLDLPGGFVDP--GESAEEALRRELREELGLKIPKLRYL--CSLPNTYLyKGITYKTCDLFFTAELD 94

                         90       100       110
                 ....*....|....*....|....*....|.
gi 490521145 116 CQPHIAS----VSDAQWVPVAELDAIELAFD 142
Cdd:cd04681   95 EKPKLKKaedeVAELEWLDLEEIEPEKLAFP 125

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: 58.57 E-value: 2.76e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  21 VTVDSVLFTLHDQalcVLLVQRARQPQQGRWALPGGFIDmqKDDSTHATALRKLTEKTGVRPSWLEQLETFSGPDRDPRG 100
Cdd:cd02883    1 VAVGAVVFDDEGR---VLLVRRSDGPGPGGWELPGGGVE--PGETPEEAAVREVREETGLDVEVLRLLGVYEFPDPDEGR 75

                         90       100       110
                 ....*....|....*....|....*....|.
gi 490521145 101 WSLTTAWFA-LIAWVDCQPHIASVSDAQWVP 130
Cdd:cd02883   76 HVVVLVFLArVVGGEPPPLDDEEISEVRWVP 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: 467589 [Multi-domain] Cd Length: 141 Bit Score: 52.36 E-value: 1.26e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  37 VLLVQRARQPQQG-RWALPGGFIDmqKDDSTHATALRKLTEKTGVRPSWLEQLETFsgpDRDPRGWSLTTawfaLIAWVD 115
Cdd:cd18877   34 VLLQHRAWWTHQGgTWALPGGARD--SGETPEAAALRETEEETGLDADTLRVVGTH---VDDHGGWSYTT----VLASAP 104

                         90       100
                 ....*....|....*....|....*...
gi 490521145 116 CQPHIASVSD----AQWVPVAELDAIEL 139
Cdd:cd18877  105 EPLPVRPANEesveLRWVPLDEVESLPL 132

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: 46.74 E-value: 1.10e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 490521145  37 VLLVQRArqpQQGRWALPGGFidMQKDDSTHATALRKLTEKTGVRPSWLEQLETFSGPD 95
Cdd:cd04677   26 ILLQKRT---DTGDWGLPGGA--MELGESLEETARREVFEETGLTVEELELLGVYSGKD 79

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: 467558 [Multi-domain] Cd Length: 118 Bit Score: 46.30 E-value: 1.16e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  15 RFPSPLVTVdsvLFTLHDQalcVLLVQRARQPQQGRWALPGGFIDMqkDDSTHATALRKLTEKTGVR--PSWLEQLETFS 92
Cdd:cd04674    1 RNPLPVVVA---LLPVRDG---LLVIRRGIEPGHGELALPGGYIEY--GETWQEAAVRELREETGVEadAAEVRLFAVRS 72


                 ....
gi 490521145  93 GPDR 96
Cdd:cd04674   73 APDG 76

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: 44.60 E-value: 4.99e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  37 VLLVQRARQPQQGRWALPGGFIDmqkDDSTHATA-LRKLTEKTGVRPSWLEQLETFSGPDRDPRgwSLTTAWFaLIAWVD 115
Cdd:cd04691   14 VLLVKRAYGPGKGRWTLPGGFVE---EGETLDEAiVREVLEETGIDAKPVGIIGVRSGVIRDGK--SDNYVVF-LLEYVG 87

                         90       100
                 ....*....|....*....|.
gi 490521145 116 CQPHIAS--VSDAQWVPVAEL 134
Cdd:cd04691   88 GEPKPDEreNSEAGFLTLEEA 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: 467588 [Multi-domain] Cd Length: 121 Bit Score: 41.80 E-value: 4.16e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  25 SVLFTlhDQALCVLLVQRARQPqqgRWALPGGFIDMqkDDSTHATALRKLTEKTGVRPSWLEQLETFSGPDRDPRGWSLT 104
Cdd:cd18876    4 GALFT--DAAGRVLLVKPTYKD---GWELPGGVVEA--GESPLQAARREVREELGLDVPVGRLLAVDWVPPAGGGDDAVL 76

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 490521145 105 TAWF------ALIAWVDCQPhiASVSDAQWVPVAELD 135
Cdd:cd18876   77 FVFDggvltpEQAAAIRLQD--EELSAYRFVTPEEAA 111

coenzyme A pyrophosphatase and similar proteins; Coenzyme A pyrophosphatase (CoAse; EC 3.6.1.1), also called nucleoside diphosphate-linked moiety X)) motif 7, is a member of the NUDIX hydrolase superfamily, functions to catalyze the elimination of oxidized inactive CoA, which can inhibit CoA-utilizing enzymes. The need of CoAses mainly arises under conditions of oxidative stress. CoAse has a conserved NUDIX fold and requires a single divalent cation for catalysis. In addition to a signature NUDIX motif G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val, CoAse contains an additional motif upstream called the NuCoA motif (LLTXT(SA)X3RX3GX3FPGG) which is postulated to be involved in CoA recognition. CoA plays a central role in lipid metabolism. It is involved in the initial steps of fatty acid sythesis in the cytosol, in the oxidation of fatty acids and the citric acid cycle in the mitochondria, and in the oxidation of long-chain fatty acids in peroxisomes. CoA has the important role of activating fatty acids for further modification into key biological signalling molecules.

Pssm-ID: 467532 [Multi-domain] Cd Length: 158 Bit Score: 41.71 E-value: 7.14e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  26 VLFTLHDQALCVLLVQRARQ--PQQGRWALPGGFIDmQKDDSTHATALRKLTEKTGVRPS---WLEQLETFsgpdrdprg 100
Cdd:cd03426    7 IPLVEGDGELHVLLTKRASHlrSHPGQIAFPGGKRE-PGDESPVETALRETEEEIGLPPEsveVLGRLDPL--------- 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 490521145 101 wsLTTAWFAL---IAWVDCQPHI----ASVSDAQWVPVAEL 134
Cdd:cd03426   77 --YTPSGFVVtpfVGLLDDPPPLrpnpDEVAEVFTVPLSFL 115

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: 40.36 E-value: 1.91e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 490521145  25 SVLFTLHDQalCVLLVQRARQPQQ--GRWALPGGFIDmqKDDSTHATALRKLTEKTGVR 81
Cdd:cd04694    6 VVLIEDSDD--RVLLTRRAKHMRTfpGVWVPPGGHVE--LGESLLEAGLRELQEETGLE 60

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: 39.21 E-value: 3.28e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 490521145  37 VLLVQRARQPQQGRWALPGGFIDMQkdDSTHATALRKLTEKTGVR 81
Cdd:cd04679   15 LLLVLRLRAPEAGHWGLPGGKVDWL--ETVEDAVRREILEELGLE 57

plant diadenosine tetraphosphate (Ap4A) hydrolase and similar proteins; Diadenosine tetraphosphate (Ap4A) hydrolase is a member of the NUDIX hydrolase superfamily. Members of this family are well represented in a variety of prokaryotic and eukaryotic organisms. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one group (represented by this subfamily) and fungi/animals/archaea enzymes 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 the inhibition of such invasive bacteria. Besides the signature NUDIX motif (G[X5]E[X7]REUXEEXGU where U is Ile, Leu, or Val), Ap4A hydrolase is structurally similar to the other members of the NUDIX hydrolase superfamily with some degree of variations. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies.

Pssm-ID: 467539 [Multi-domain] Cd Length: 147 Bit Score: 39.47 E-value: 3.60e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  37 VLLVQRARQPqqGRWALPGGFIDmqKDDSTHATALRKLTEKTGVRPSWLEQL----ETFS---GPDRDPRGWSLTTA--- 106
Cdd:cd03671   17 VLVGRRIDVP--GAWQFPQGGID--EGEDPEEAALRELYEETGLSPEDVEIIaetpDWLTydlPEDLIRKGWGGKYRgqk 92

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 490521145 107 --WFAL-----IAWVDCQPHI-ASVSDAQWVPVAELDAIELAF 141
Cdd:cd03671   93 qkWFLFrftgdDSEINLDTHEhPEFDAWRWVDLEELPDLVVPF 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.

Pssm-ID: 467590 [Multi-domain] Cd Length: 142 Bit Score: 39.49 E-value: 3.91e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  16 FPSPLVTVDSVLFtlhDQALCVLLVQRArqpQQGRWALPGGFIDmqKDDSTHATALRKLTEKTGV-----RPSWLEQLET 90
Cdd:cd18879   14 DPLWLPGVTAVVL---RDAGRVLLVRRA---DNGRWTPVTGIVE--PGEQPADAAVREVLEETGVdveveRLASVGASPP 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 490521145  91 FSGPDRDPRGWsLTTaWFALiAWVDCQPHIA--SVSDAQWVPVAELDaiELAFDHQTIIEAA 150
Cdd:cd18879   86 VTYPNGDQCQY-LDL-TFRC-RPVGGEARVNddESLEVGWFPVDALP--PMLPRFRRRIALA 142

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: 467545 [Multi-domain] Cd Length: 123 Bit Score: 39.10 E-value: 4.58e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 490521145  37 VLLVQRARQPQQGRWALPGGFidMQKDDSTHATALRKLTEKTGVR 81
Cdd:cd04511   15 VLLCRRAIEPRKGYWTLPAGF--MELGETTEQGAARETREEAGAR 57

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: 467552 [Multi-domain] Cd Length: 117 Bit Score: 38.42 E-value: 6.33e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 490521145  37 VLLVQRARqpqqGRWALPGGFIdmQKDDSTHATALRKLTEKTGVRPSWLEQLETFSGPDRDP 98
Cdd:cd04667   13 ILLVARRG----GRWLLPGGKI--EPGESPLEAAIRELKEETGLAALSLLYLFEHEGPHKLH 68

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: 38.39 E-value: 7.62e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  37 VLLVqraRQPQQGRWALPGGFIDmqKDDSTHATALRKLTEKTGVRPSWLEQ-------LETFSGPDRDPRG----WSLTt 105
Cdd:cd03674   16 VLLV---HHRKLGRWLQPGGHVE--PDEDPLEAALREAREETGLDVELLSPlspdpldIDVHPIPANPGEPahlhLDVR- 89

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 490521145 106 awFALIAWVDCQPHIAS-VSDAQWVPVAELDAIEL 139
Cdd:cd03674   90 --YLAVADGDEALRKSDeSSDVRWFPLDELEELSM 122

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: 467596 [Multi-domain] Cd Length: 147 Bit Score: 38.75 E-value: 7.83e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 490521145  37 VLLVQRARQPQQGRWALPGGFIDMqkDDSTHATALRKLTEKTGVRpswLEQLE-----TFSGPDRDPRG 100
Cdd:cd18886   13 VLLLNRNKKPNMGKWNGVGGKLEP--GESPEECAIREVFEETGLE---LEDLQlrgivTFPSFDGGEDW 76

AraR C-terminal winged HTH domain; This entry represents the C-terminal DNA-binding domain of AraR proteins which are involved in regulating Arabinose utilization. This domain has a winged helix-turn-helix structure.

Pssm-ID: 437200 Cd Length: 82 Bit Score: 37.03 E-value: 1.18e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  160 YSLLPVYCLPECFTLSQLQEATEIILGQPIQRKSLIR-RFEASGMFEETGESVATGA-RKARLWRRKPDA 227
Cdd:pfam19368   1 YSPIAFDVLPELFTLNDLYQFYTTVLGENFSDYSNFRtRLLKLGFLSDTGKKVSRGAgRPASLYRFDAEA 70

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: 37.99 E-value: 1.53e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 490521145  19 PLVTVDSVLFTLHDQalcVLLVQRARQPQQGRWALPGGFIdmQKDDSTHATALRKLTEKTGV 80
Cdd:cd03430   14 PLVSIDLIIRNEDGE---ILLGKRNNRPAQGYWFVPGGRI--LKNETLDDAFKRIAREELGL 70

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: 37.53 E-value: 1.70e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 490521145  26 VLFTLHDQALCVLLVQrarQPQQGRWALPGGFIDmqKDDSTHATALRKLTEKTGVRPS 83
Cdd:cd03428    8 IIYRRDNGEIEFLLLQ---HSYGGHWDFPKGHVE--PGESELETALRETKEETGLTVD 60

GDP-mannose mannosyl hydrolase;

Pssm-ID: 237966 [Multi-domain] Cd Length: 159 Bit Score: 37.04 E-value: 3.14e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 490521145  18 SPLVTVDsvlFTLHDQALCVLLVQRARQPQQGRWALPGGFIdmQKDDsTHATALRKLTEKT-GVR 81
Cdd:PRK15434  15 TPLISLD---FIVENSRGEFLLGKRTNRPAQGYWFVPGGRV--QKDE-TLEAAFERLTMAElGLR 73

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: 467569 [Multi-domain] Cd Length: 130 Bit Score: 36.50 E-value: 3.69e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490521145  36 CVLLVQRARQPQQGRWALPGGfiDMQKDDSTHATALRKLTEKTGVRPSWLEQLETFSgpDRDPRGWSLTT---------- 105
Cdd:cd04686   13 KLLLIRKTRGPYQGRYDLPGG--SQEFGESLEDALKREFAEETGMTVTSYDNLGVYD--FFVPWSDKELGdvhhigvfyd 88

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 490521145 106 --AWFALIAwvdcQPHIASVSD---AQWVPVAELDAI 137
Cdd:cd04686   89 veLLDNNIS----ELLQFEGQDslgAVWIPLQDLTEL 121

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: 36.00 E-value: 4.40e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 490521145  36 CVLLVQRARQPQQGRWALPGGFIDMqkDDSTHATALRKLTEKTGVR 81
Cdd:cd04678   15 KVLLGRRKGSHGAGTWALPGGHLEF--GESFEECAAREVLEETGLE 58

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: 35.31 E-value: 9.44e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 490521145  30 LHDQALCVLLVQRARQP---QQGRWALPGGFIDmqKDDSTHATALRKLTEKTGVRPS 83
Cdd:cd18882    8 LYDDRGKVLLQLRDDKPgipYPGYWGLFGGHLE--PGETPEEAIRRELEEEIGYEPG 62