Catalytic domain of EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins; Catalytic domain of an EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins. Nuc is an endonuclease cleaving both single- and double-stranded DNA. It is the smallest known member of the phospholipase D (PLD, EC 3.1.4.4) superfamily that includes a diverse group of proteins with various catalytic functions. Most members of this superfamily have two copies of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in a single polypeptide chain and both are required for catalytic activity. However, Nuc only has one copy of the HKD motif per subunit but form a functionally active homodimer (it is most likely also active in solution as a multimeric protein), which has a single active site at the dimer interface containing the HKD motifs from both subunits. Due to the lack of a distinct domain for DNA binding, Nuc cuts DNA non-specifically. It utilizes a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  29 SIETGYSPEGTALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKRRGVDVKVVLDWKANTGKQnqaslAAMNLLVNA 108
Cdd:cd09170    1 TVEVYFSPEGGARELILDVIDSARRSIDVAAYSFTSPPIARALIAAKKRGVDVRVVLDKSQAGGKY-----SALNYLANA 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 502979020 109 GIPVRTVSQYKIMHDKVIIADGRNIEVGSFNYTRSADRVNSENVLVVWDVPVVAQRYLQHWSTRWSQ 175
Cdd:cd09170   76 GIPVRIDDNYAIMHNKVMVIDGKTVITGSFNFTASAEKRNAENLLVIRNPPELAQQYLQEWQRRWAQ 142

Catalytic domain of EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins; Catalytic domain of an EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins. Nuc is an endonuclease cleaving both single- and double-stranded DNA. It is the smallest known member of the phospholipase D (PLD, EC 3.1.4.4) superfamily that includes a diverse group of proteins with various catalytic functions. Most members of this superfamily have two copies of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in a single polypeptide chain and both are required for catalytic activity. However, Nuc only has one copy of the HKD motif per subunit but form a functionally active homodimer (it is most likely also active in solution as a multimeric protein), which has a single active site at the dimer interface containing the HKD motifs from both subunits. Due to the lack of a distinct domain for DNA binding, Nuc cuts DNA non-specifically. It utilizes a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  29 SIETGYSPEGTALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKRRGVDVKVVLDWKANTGKQnqaslAAMNLLVNA 108
Cdd:cd09170    1 TVEVYFSPEGGARELILDVIDSARRSIDVAAYSFTSPPIARALIAAKKRGVDVRVVLDKSQAGGKY-----SALNYLANA 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 502979020 109 GIPVRTVSQYKIMHDKVIIADGRNIEVGSFNYTRSADRVNSENVLVVWDVPVVAQRYLQHWSTRWSQ 175
Cdd:cd09170   76 GIPVRIDDNYAIMHNKVMVIDGKTVITGSFNFTASAEKRNAENLLVIRNPPELAQQYLQEWQRRWAQ 142

Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase [Lipid transport and metabolism]; Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase is part of the Pathway/BioSystem: Phospholipid biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  17 SLFAPFPVVYADSIETGYSPEgTALQLVLKTINSAQQEIRLMGYSFTSPE----VAGALVRAKRRGVDVKVVLDWKANTG 92
Cdd:COG1502    4 PLAAGLPLVGGNRVTLLVDGD-EAFAALLEAIEAARRSIDLEYYIFDDDEvgrrLADALIAAARRGVKVRVLLDGIGSRA 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 502979020  93 kqnqASLAAMNLLVNAGIPVRT--------VSQYKIMHDKVIIADGRNIEVGSFNYT 141
Cdd:COG1502   83 ----LNRDFLRRLRAAGVEVRLfnpvrllfRRLNGRNHRKIVVIDGRVAFVGGANIT 135

Catalytic domain of EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins; Catalytic domain of an EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins. Nuc is an endonuclease cleaving both single- and double-stranded DNA. It is the smallest known member of the phospholipase D (PLD, EC 3.1.4.4) superfamily that includes a diverse group of proteins with various catalytic functions. Most members of this superfamily have two copies of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in a single polypeptide chain and both are required for catalytic activity. However, Nuc only has one copy of the HKD motif per subunit but form a functionally active homodimer (it is most likely also active in solution as a multimeric protein), which has a single active site at the dimer interface containing the HKD motifs from both subunits. Due to the lack of a distinct domain for DNA binding, Nuc cuts DNA non-specifically. It utilizes a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  29 SIETGYSPEGTALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKRRGVDVKVVLDWKANTGKQnqaslAAMNLLVNA 108
Cdd:cd09170    1 TVEVYFSPEGGARELILDVIDSARRSIDVAAYSFTSPPIARALIAAKKRGVDVRVVLDKSQAGGKY-----SALNYLANA 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 502979020 109 GIPVRTVSQYKIMHDKVIIADGRNIEVGSFNYTRSADRVNSENVLVVWDVPVVAQRYLQHWSTRWSQ 175
Cdd:cd09170   76 GIPVRIDDNYAIMHNKVMVIDGKTVITGSFNFTASAEKRNAENLLVIRNPPELAQQYLQEWQRRWAQ 142

Catalytic domain of vertebrate phospholipase D6 and similar proteins; Catalytic domain of vertebrate phospholipase D6 (PLD6, EC 3.1.4.4), a homolog of the EDTA-resistant nuclease Nuc from Salmonella typhimurium, and similar proteins. PLD6 can selectively hydrolyze the terminal phosphodiester bond of phosphatidylcholine (PC) with the formation of phosphatidic acid and alcohols. Phosphatidic acid is an essential compound involved in signal transduction. It also catalyzes the transphosphatidylation of phospholipids to acceptor alcohols, by which various phospholipids can be synthesized. PLD6 belongs to the phospholipase D (PLD) superfamily. Its monomer contains a short conserved sequence motif, H-x-K-x(4)-D (where x represents any amino acid residue), termed the HKD motif, which is essential in catalysis. PLD6 is more closely related to the nuclease Nuc than to other vertebrate phospholipases, which have two copies of the HKD motif in a single polypeptide chain. Like Nuc, PLD6 may utilize a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from the HKD motif of one subunit to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  34 YSPEGTALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKRRGVDVKVVLDWKANTGKQNQaslaaMNLLVNAGIPVR 113
Cdd:cd09171    3 FFPGETSLSKLLRYLLSARKSLDVCVFTITCDDLADAILDLHRRGVRVRIITDDDQMEDKGSD-----IGKLRKAGIPVR 77

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 502979020 114 TVSQYKIMHDKVIIADGRNIEVGSFNYTRSADRVNSEN 151
Cdd:cd09171   78 TDLSSGHMHHKFAVIDGKILITGSFNWTRQAVTGNQEN 115

Putative catalytic domain of uncharacterized phospholipase D-like proteins; Putative catalytic domain of uncharacterized phospholipase D (PLD, EC 3.1.4.4)-like proteins. Members of this subfamily contain one copy of HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the PLD superfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  44 VLKTINSAQQEIRLMGYSFTSPEVAG--------ALVRAKRRGVDVKVVLDWKANTGKQNQASLAAMNLLVNAGIPVRTV 115
Cdd:cd09131    8 LLDLINNAKRSIYIAMYMFKYYENPGngvntlleALIDAHKRGVDVKVVLEDSIDDDEVTEENDNTYRYLKDNGVEVRFD 87

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 502979020 116 SQYKIMHDKVIIADGRNIEVGSFNYTRSADRVNSE 150
Cdd:cd09131   88 SPSVTTHTKLVVIDGRTVYVGSHNWTYSALDYNHE 122

Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase [Lipid transport and metabolism]; Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase is part of the Pathway/BioSystem: Phospholipid biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  17 SLFAPFPVVYADSIETGYSPEgTALQLVLKTINSAQQEIRLMGYSFTSPE----VAGALVRAKRRGVDVKVVLDWKANTG 92
Cdd:COG1502    4 PLAAGLPLVGGNRVTLLVDGD-EAFAALLEAIEAARRSIDLEYYIFDDDEvgrrLADALIAAARRGVKVRVLLDGIGSRA 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 502979020  93 kqnqASLAAMNLLVNAGIPVRT--------VSQYKIMHDKVIIADGRNIEVGSFNYT 141
Cdd:COG1502   83 ----LNRDFLRRLRAAGVEVRLfnpvrllfRRLNGRNHRKIVVIDGRVAFVGGANIT 135

Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase [Lipid transport and metabolism]; Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase is part of the Pathway/BioSystem: Phospholipid biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  35 SPEGTALQLVLKTINSAQQEIRLMGYSFT-SPEVAGALVRAKRRGVDVKVVLDWKANTGKQNQASLAAMNLLVNAGIPVR 113
Cdd:COG1502  199 SPRETIERALLAAIASARRRIYIETPYFVpDRSLLRALIAAARRGVDVRILLPAKSDHPLVHWASRSYYEELLEAGVRIY 278

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 502979020 114 tvsQYK--IMHDKVIIADGRNIEVGSFNYTRSADRVNSEN 151
Cdd:COG1502  279 ---EYEpgFLHAKVMVVDDEWALVGSANLDPRSLRLNFEV 315

nuclease NucT; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  40 ALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKRRGVDVKVVLDWKANTG-KQNQ----ASLAAMNLLVNAGIPVRT 114
Cdd:PRK13912  34 ALNKLVSLISNARSSIKIAIYSFTHKDIAKALKSAAKRGVKISIIYDYESNHNnDQSTigylDKYPNIKVCLLKGLKAKN 113

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 502979020 115 VSQYKIMHDKVIIADGRNIEVGSFNYTRSADRVNSEN 151
Cdd:PRK13912 114 GKYYGIMHQKVAIIDDKIVVLGSANWSKNAFENNYEV 150

Putative catalytic domain of uncharacterized phospholipase D-like proteins; Putative catalytic domain of uncharacterized phospholipase D (PLD, EC 3.1.4.4)-like proteins. Members of this subfamily contain one copy of HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the PLD superfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  42 QLVLKTINSAQQEIRLMGYSFTS-PEVAGALVRAKRRGVDVKVVLDW-KANTGKQNQASLAAM-NLLVNAGIPVRTVSQY 118
Cdd:cd09132    2 QVLLELIEGAERSLLIVGYSAYKvSELLQALAAALERGVQVRVVVESsEKAGSVLSLDEDELMwPKLAGATLYVWPEKKR 81

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 502979020 119 K----IMHDKVIIADGRNIEVGSFNYTRSADRVNSE 150
Cdd:cd09132   82 PgkraSLHAKVIVADRRRLLVTSANLTGAGMERNIE 117

Catalytic domain, repeat 1, of bacterial cardiolipin synthase and similar proteins; Catalytic domain, repeat 1, of bacterial cardiolipin (CL) synthase and a few homologs found in eukaryotes and archaea. Bacterial CL synthases catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. The monomer of bacterial CL synthase consists of two catalytic domains. Each catalytic domain contains one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. Two HKD motifs from two domains form a single active site involved in phosphatidyl group transfer. Bacterial CL synthases can be stimulated by phosphate and inhibited by CL, the product of the reaction, and by phosphatidate. Phosphate stimulation may be unique to enzymes with CL synthase activity belonging to the PLD superfamily. Like other PLD enzymes, bacterial CL synthases utilize a common two-step ping-pong catalytic mechanism involving an enzyme-substrate intermediate to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine residue from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  45 LKTINSAQQEIRLMGYSFTSPEVAG----ALVRAKRRGVDVKVVLDWkANTGKQNQASLAAmnlLVNAGIPVRT---VSQ 117
Cdd:cd09110   11 LEAIRAARHSIHLEYYIFRDDEIGRrfrdALIEKARRGVEVRLLYDG-FGSLGLSRRFLRE---LREAGVEVRAfnpLSF 86

                         90       100       110
                 ....*....|....*....|....*....|..
gi 502979020 118 YKI-------MHDKVIIADGRNIEVGSFNYTR 142
Cdd:cd09110   87 PLFllrlnyrNHRKILVIDGKIAFVGGFNIGD 118

Putative catalytic domain, repeat 2, of uncharacterized hypothetical proteins similar to Nuc, an endonuclease from Salmonella typhimurium; Putative catalytic domain, repeat 2, of uncharacterized hypothetical proteins, which show high sequence homology to the endonuclease from Salmonella typhimurium and vertebrate phospholipase D6. Nuc and PLD6 belong to the phospholipase D (PLD) superfamily. They contain a short conserved sequence motif, the HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which characterizes the PLD superfamily and is essential for catalysis. Nuc and PLD6 utilize a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit. However, proteins in this subfamily have two HKD motifs in a single polypeptide chain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  37 EGTALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKRRGVDVKVVLDwkANTGKQNQASLAAMNLLVNAGI------ 110
Cdd:cd09173    7 GNADLALIAELVAKAKSSVLFALFDFSDGALLDALLAAADAGLFVRGLVD--KRFGGRYYSAAADMGGIDPVYPaalapd 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 502979020 111 -PVRTVSQYK-----IMHDKVIIADGRNIE----VGSFNYTRSADRVNSEN 151
Cdd:cd09173   85 ePEKFVGEPLlgvgdKLHHKFMVIDPFGDDpvviTGSHNFSGAANDNNDEN 135

Putative catalytic domain, repeat 1, of Escherichia coli uncharacterized protein ymdC and similar proteins; Putative catalytic domain, repeat 1, of Escherichia coli uncharacterized protein ymdC and similar proteins. In Escherichia coli, there are two genes, f413 (ybhO) and o493 (ymdC), which are homologous to gene cls that encodes the Escherichia coli cardiolipin (CL) synthase. The prototype of this subfamily is an uncharacterized protein ymdC specified by the o493 (ymdC) gene. Although the functional characterization of ymdC and similar proteins remains unknown, members of this subfamily show high sequence homology to bacterial CL synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Moreover, ymdC and its similar proteins contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characteriszes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  40 ALQLVLKTINSAQQEIRLMGYSFTSPE----VAGALVRAKRRGVDVKVVLDwKANTGKQNQAsLAAMNLlvNAGIPVR-- 113
Cdd:cd09111    7 ALAARLALIRSAERSIDLQYYIWHDDEsgrlLLGELLEAADRGVRVRLLLD-DLGTSGRDRL-LAALDA--HPNIEVRlf 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 502979020 114 --TVSQYKI--------------MHDKVIIAD-------GRNI 133
Cdd:cd09111   83 npFRNRGGRllefltdfsrlnrrMHNKLFIVDgavaivgGRNI 125

Putative catalytic domain, repeat 2, of uncharacterized proteins similar to bacterial cardiolipin synthase; Putative catalytic domain, repeat 2, of uncharacterized proteins similar to bacterial cardiolipin (CL) synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Members of this subfamily contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  36 PEGTALQLVLKTINSAQQEIRLMGYSFTSPEV-AGALVRAKRRGVDVKVVLDWKANTGKQNQASLAAMNLLVNAGIPVRT 114
Cdd:cd09162    8 PGDPLYEALLSAIFEAEHRIWIVTPYFVPDEVlLRALRLAARRGVDVRLIVPKRSNHRIADLARGSYLRDLQEAGAEIYL 87

                         90       100
                 ....*....|....*....|....*
gi 502979020 115 VsQYKIMHDKVIIADGRNIEVGSFN 139
Cdd:cd09162   88 Y-QPGMLHAKAVVVDDKLALVGSAN 111

Putative catalytic domain, repeat 1, of vertebrate phospholipases, PLD3, PLD4 and PLD5, viral envelope proteins K4 and p37, and similar proteins; Putative catalytic domain, repeat 1, of vertebrate phospholipases D, PLD3, PLD4, and PLD5 (EC 3.1.4.4), viral envelope proteins (vaccinia virus proteins K4 and p37), and similar proteins. Most family members contain two copies of the HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue), and have been classified into the phospholipase D (PLD) superfamily. Proteins in this subfamily are associated with Golgi membranes, altering their lipid content by the conversion of phospholipids into phosphatidic acid, which is thought to be involved in the regulation of lipid movement. ADP ribosylation factor (ARF), a small guanosine triphosphate binding protein, might be required activity. The vaccinia virus p37 protein, encoded by the F13L gene, is also associated with Golgi membranes and is required for the envelopment and spread of the extracellular enveloped virus (EEV). The vaccinia virus protein K4, encoded by the HindIII K4L gene, remains to be characterized. Sequence analysis indicates that the vaccinia virus proteins K4 and p37 might have evolved from one or more captured eukaryotic genes involved in cellular lipid metabolism. Up to date, no catalytic activity of PLD3 has been shown. Furthermore, due to the lack of functional important histidine and lysine residues in the HKD motif, mammalian PLD5 has been characterized as an inactive PLD. The poxvirus p37 proteins may also lack PLD enzymatic activity, since they contain only one partially conserved HKD motif (N-x-K-x(4)-D).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  70 ALVRAKRRGVDVKVVLDwKANTGKQNQASLAAMNLlvnAGIPVRTVSQYK-----IMHDKVIIADGRNIEVGSFNYT-RS 143
Cdd:cd09106   64 ALLEAAKRGVKIRILQD-KPSKDKPDEDDLELAAL---GGAEVRSLDFTKligggVLHTKFWIVDGKHFYLGSANLDwRS 139

Middle phospholipase D-like domain of the transcriptional regulator TrmB and similar proteins; Middle phospholipase D (PLD)-like domain of the transcriptional regulator TrmB and similar proteins. TrmB acts as a bifunctional sugar-sensing transcriptional regulator which controls two operons encoding maltose/trehalose and maltodextrin ABC transporters of Pyrococcus fruiosus. It functions as a dimer. Full length TrmB includes an N-terminal DNA-binding domain, a C-terminal sugar-binding domain and middle region that has been named as a PLD-like domain. The middle domain displays homology to PLD enzymes, which contain one or two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) per chain. The HKD motif characterizes the PLD superfamily. Due to the lack of key residues related to PLD activity in the PLD-like domain, members of this subfamily are unlikely to carry PLD activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  37 EGTALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKRRGVDVKVVLDWKANTGKqnqaslaamnlLVNAGIPVRTVS 116
Cdd:cd09124    8 EENILAKIREMINSAKEEIYISLPSEELEELLEELEKAAERGVKVVIIIFGDDDLDD-----------LDSPAIEVRVRE 76

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 502979020 117 QYKimHDKVIIADGRNIEVGSFNYTRSADRVNSEN 151
Cdd:cd09124   77 GGG--RPFLLIVDSKEALIGPSSEEEETYALYTEN 109

Catalytic domain, repeat 1, of Escherichia coli cardiolipin synthase and similar proteins; Catalytic domain, repeat 1, of Escherichia coli cardiolipin (CL) synthase and similar proteins. Escherichia coli CL synthase (EcCLS), specified by the cls gene, is the prototype of this family. EcCLS is a multi-pass membrane protein that catalyzes reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form cardiolipin (CL) and glycerol. The monomer of EcCLS consists of two catalytic domains. Each catalytic domain contains one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. Two HKD motifs from two domains form a single active site involved in phosphatidyl group transfer. EcCLS can be stimulated by phosphate and inhibited by CL, the product of the reaction, and by phosphatidate. Phosphate stimulation may be unique to enzymes with CL synthase activity belonging to the PLD superfamily. Like other PLD enzymes, EcCLS utilizes a common two-step ping-pong catalytic mechanism involving an enzyme-substrate intermediate to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine residue from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  39 TALQLVLKTINSAQQEIRLMGYSF----TSPEVAGALVRAKRRGVDVKVVLD-------WKANTGKQNQASLAAMNLLVN 107
Cdd:cd09152   12 AVIDRLIADIDAAKHHVHLLFYIWaddgTGDRVAEALERAAKRGVTCRLLLDavgsrafFRSSLWKRLREAGVEVVEALP 91

                         90       100       110
                 ....*....|....*....|....*....|...
gi 502979020 108 AGIPVRTVSQYKIM-HDKVIIADGRNIEVGSFN 139
Cdd:cd09152   92 LRLFRRRLARFDLRnHRKIAVIDGRIAYTGSQN 124

cardiolipin synthetase; Reviewed

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  36 PEGTALQLVLKTINSAQQEIRLmgysfTSP------EVAGALVRAKRRGVDVKVVLDWKANTGKQNQASLAAMNLLVNAG 109
Cdd:PRK01642 315 PEETIHQFLLTAIYSARERLWI-----TTPyfvpdeDLLAALKTAALRGVDVRIIIPSKNDSLLVFWASRAFFTELLEAG 389

                         90       100       110
                 ....*....|....*....|....*....|..
gi 502979020 110 IpvrTVSQYK--IMHDKVIIADGRNIEVGSFN 139
Cdd:PRK01642 390 V---KIYRYEggLLHTKSVLVDDELALVGTVN 418

Putative catalytic domain, repeat 1, of uncharacterized proteins similar to bacterial cardiolipin synthase; Putative catalytic domain, repeat 1, of uncharacterized proteins similar to bacterial cardiolipin (CL) synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Members of this subfamily contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 502979020  45 LKTINSAQQEIRLMGYSFTSPEV----AGALVRAKRRGVDVKVVLD 86
Cdd:cd09157   11 LEAIDAARHSIALSSYIFDNDGVgrefVDALAEAVARGVDVRVLID 56

N-terminal phospholipase D-like domain of the protein, Family with sequence similarity 83D; N-terminal phospholipase D (PLD)-like domain of the protein Family with sequence similarity 83D (FAM83D), also known as spindle protein CHICA. CHICA is a cell-cycle-regulated spindle component, which localizes to the mitotic spindle and is both upregulated and phosphorylated during mitosis. CHICA is required to localize the chromokinesin Kid to the mitotic spindle and serves as a novel interaction partner of Kid, which is required for the generation of polar ejection forces and chromosome congression. Since the N-terminal PLD-like domain of FAM83D shows only trace similarity to the PLD catalytic domain and lacks the functionally important histidine residue, FAM83D may share a similar three-dimensional fold with PLD enzymes, but is unlikely to carry PLD activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  48 INSAQQEIRLMGYSFTSPEVAGALVRA-KRRGVDVKVVLDwkantgkqnQASLA-----AMNLLVNAG----IPVRTV-- 115
Cdd:cd09184  133 IRSAREVIALVMDSFTDLDIFRDLREAcRKRRVPVYILLD---------QSSVShflqmCKNLGVHLEqeklMRVRTItg 203

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 502979020 116 ------SQYKI---MHDKVIIADGRNIEVGSFNYTRSADRVNSEN 151
Cdd:cd09184  204 ntyytrSGAKIigkVHEKFMLIDGIKVATGSYSFTWTDGKLNSSN 248

Catalytic domain, repeat 2, of Escherichia coli cardiolipin synthase and similar proteins; Catalytic domain, repeat 2, of Escherichia coli cardiolipin (CL) synthase and similar proteins. Escherichia coli CL synthase (EcCLS), specified by the cls gene, is the prototype of this family. EcCLS is a multi-pass membrane protein that catalyzes reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form cardiolipin (CL) and glycerol. The monomer of EcCLS consists of two catalytic domains. Each catalytic domain contains one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. Two HKD motifs from two domains form a single active site involved in phosphatidyl group transfer. EcCLS can be stimulated by phosphate and inhibited by CL, the product of the reaction, and by phosphatidate. Phosphate stimulation may be unique to enzymes with CL synthase activity belonging to the PLD superfamily. Like other PLD enzymes, EcCLS utilizes a common two-step ping-pong catalytic mechanism involving an enzyme-substrate intermediate to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine residue from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502979020  36 PEGTALQLVLKTINSAQQEIRLmgysfTSP------EVAGALVRAKRRGVDVKVVLDWKANtgkQNQASLAAMNL---LV 106
Cdd:cd09158    8 PTENIPQLLLSAIHAARRRVVI-----TTPyfvpdeSLLQALCTAALRGVEVTLILPAKND---SFLVGAASRSYyeeLL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 502979020 107 NAGIPVRtvsQYK--IMHDKVIIADGRNIEVGSFNYTRSADRVNSENV 152
Cdd:cd09158   80 EAGVKIY---LYRggLLHAKTVTVDDEVALVGSSNFDIRSFALNFEIS 124