catalytic domain repeat 2 of bacterial cardiolipin synthase and similar proteins; This CD corresponds to the catalytic domain repeat 2 of bacterial cardiolipin synthase (CL synthase, EC 2.7.8.-) and a few homologs found in eukaryotes and archea. Bacterial CL synthases catalyze reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form cardiolipin (CL) and glycerol. The monomer of bacterial CL synthase consists of two catalytic domains. Each catalytic domain contains one copy of conserved HKD motifs (H-X-K-X(4)-D, X represents any amino acid residue) that are the characteristic of the phospholipase D (PLD) superfamily. Two HKD motifs from two domains together form a single active site involving 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 in PLD superfamily. Like other PLD enzymes, bacterial CL synthase 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 2784295957   2 GVSVKILVPKDPDlTGFFKAMNRQLFSILLDQDIEIYEY-FGFNHEKVMIIDDEIVYFGSYNWDYRSLYLNFENALLVRS 80
Cdd:cd09112    51 GVDVRIMIPGKPD-HKLVYWASRSYFEELLKAGVKIYEYnKGFLHSKTLIVDDEIASVGTANLDIRSFELNFEVNAVIYD 129

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2784295957  81 EKVSAVMSDFMNRQFANSKQINRSDLKK-SVNTPFKNSFIRLFKP 124
Cdd:cd09112   130 KEVAKKLEEIFEEDLKDSELLTLEEWRKrSLWKRFKESLARLLSP 174

cardiolipin synthetase; Reviewed

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2784295957   2 GVSVKILVPKDPDLTGFFKAmNRQLFSILLDQDIEIYEYF-GFNHEKVMIIDDEIVYFGSYNWDYRSLYLNFE-NALLVR 79
Cdd:PRK01642  358 GVDVRIIIPSKNDSLLVFWA-SRAFFTELLEAGVKIYRYEgGLLHTKSVLVDDELALVGTVNLDMRSFWLNFEiTLVIDD 436

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2784295957  80 SEKVSAVMSDFMNrQFANSKQINRSD-LKKSVNTPFKNSFIRLFKPFL 126
Cdd:PRK01642  437 TGFAADLAAMQED-YFARSRELDLEEwRKRPLWQRIAERVARLFSPLL 483

Phospholipase D. Active site motifs; Phosphatidylcholine-hydrolyzing phospholipase D (PLD) isoforms are activated by ADP-ribosylation factors (ARFs). PLD produces phosphatidic acid from phosphatidylcholine, which may be essential for the formation of certain types of transport vesicles or may be constitutive vesicular transport to signal transduction pathways. PC-hydrolysing PLD is a homologue of cardiolipin synthase, phosphatidylserine synthase, bacterial PLDs, and viral proteins. Each of these appears to possess a domain duplication which is apparent by the presence of two motifs containing well-conserved histidine, lysine, aspartic acid, and/or asparagine residues which may contribute to the active site. An E. coli endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs. The profile contained here represents only the putative active site regions, since an accurate multiple alignment of the repeat units has not been achieved.

                           10        20
                   ....*....|....*....|....*...
gi 2784295957   40 YFGFNHEKVMIIDDEIVYFGSYNWDYRS 67
Cdd:smart00155   1 YDGVLHTKLMIVDDEIAYIGSANLDGRS 28

catalytic domain repeat 2 of bacterial cardiolipin synthase and similar proteins; This CD corresponds to the catalytic domain repeat 2 of bacterial cardiolipin synthase (CL synthase, EC 2.7.8.-) and a few homologs found in eukaryotes and archea. Bacterial CL synthases catalyze reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form cardiolipin (CL) and glycerol. The monomer of bacterial CL synthase consists of two catalytic domains. Each catalytic domain contains one copy of conserved HKD motifs (H-X-K-X(4)-D, X represents any amino acid residue) that are the characteristic of the phospholipase D (PLD) superfamily. Two HKD motifs from two domains together form a single active site involving 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 in PLD superfamily. Like other PLD enzymes, bacterial CL synthase 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 2784295957   2 GVSVKILVPKDPDlTGFFKAMNRQLFSILLDQDIEIYEY-FGFNHEKVMIIDDEIVYFGSYNWDYRSLYLNFENALLVRS 80
Cdd:cd09112    51 GVDVRIMIPGKPD-HKLVYWASRSYFEELLKAGVKIYEYnKGFLHSKTLIVDDEIASVGTANLDIRSFELNFEVNAVIYD 129

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2784295957  81 EKVSAVMSDFMNRQFANSKQINRSDLKK-SVNTPFKNSFIRLFKP 124
Cdd:cd09112   130 KEVAKKLEEIFEEDLKDSELLTLEEWRKrSLWKRFKESLARLLSP 174

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 2784295957   2 GVSVKILVPKDPDLTGFFKAMNRQLFSiLLDQDIEIYEYFG-FNHEKVMIIDDEIVYFGSYNWDYRSLYLNFENALLVRS 80
Cdd:cd09163    51 GVEVDIVLPERNNLPLVDWAMRANLWE-LLEHGVRIYLQPPpFDHSKLMVVDGAWALIGSANWDPRSLRLNFELNLEVYD 129

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2784295957  81 EKVSAVMSDFMNRQFANSKQINRSDLKK-SVNTPFKNSFIRLFKPFL 126
Cdd:cd09163   130 TALAGQLDALFDSKIAKSREVTLEELDArPLPIRLRDAAARLFSPYL 176

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 2784295957   1 MGVSVKILVPKDPD--LTGffkAMNRQLFSILLDQDIEIYEYF-GFNHEKVMIIDDEIVYFGSYNWDYRSLYLNFENALL 77
Cdd:cd09158    50 RGVEVTLILPAKNDsfLVG---AASRSYYEELLEAGVKIYLYRgGLLHAKTVTVDDEVALVGSSNFDIRSFALNFEISLI 126

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2784295957  78 VRSEKVSAVMSDFMNRQFANSKQINRSDLKK-SVNTPFKNSFIRLFKP 124
Cdd:cd09158   127 LYDKEFTAQLRAIQERYLARSDPLTLEEWKKrPLWRRLLENLARLLSP 174

cardiolipin synthetase; Reviewed

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2784295957   2 GVSVKILVPKDPDLTGFFKAmNRQLFSILLDQDIEIYEYF-GFNHEKVMIIDDEIVYFGSYNWDYRSLYLNFE-NALLVR 79
Cdd:PRK01642  358 GVDVRIIIPSKNDSLLVFWA-SRAFFTELLEAGVKIYRYEgGLLHTKSVLVDDELALVGTVNLDMRSFWLNFEiTLVIDD 436

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2784295957  80 SEKVSAVMSDFMNrQFANSKQINRSD-LKKSVNTPFKNSFIRLFKPFL 126
Cdd:PRK01642  437 TGFAADLAAMQED-YFARSRELDLEEwRKRPLWQRIAERVARLFSPLL 483

Putative catalytic domain, repeat 2, of Escherichia coli uncharacterized protein ymdC and similar proteins; Putative catalytic domain, repeat 2, 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 2784295957  30 LLDQDIEIYEY-------------FGFN----HEKVMIIDDEIVYFGSYNWDYRSLYLNFENALLVRSEKVSAVMSDFMN 92
Cdd:cd09113    86 LLKAGVELYELkpdaakrkrlrglFGSSraslHAKSFVIDDRLVFVGSFNLDPRSAYLNTEMGLVIDSPELAAQLRAAME 165

                  ....*.
gi 2784295957  93 RQFANS 98
Cdd:cd09113   166 EDLAPS 171

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 2784295957   2 GVSVKILVPKDPDLTGFFKAMNRQLFSiLLDQDIEIYEYFGFN-HEKVMIIDDEIVYFGSYNWDYRSLYLNFENALLVRS 80
Cdd:cd09162    51 GVDVRLIVPKRSNHRIADLARGSYLRD-LQEAGAEIYLYQPGMlHAKAVVVDDKLALVGSANLDMRSLFLNYEVAVFFYS 129

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2784295957  81 EKVSAVMSDFMNRQFANS--KQINRSDLKKSVntpfkNSFIRLFKPFL 126
Cdd:cd09162   130 PADIKELSDWIESLISQCteGAPPPSALRDIA-----EGLMRLLAPLL 172

Catalytic domain of phospholipase D superfamily proteins; Catalytic domain of phospholipase D (PLD) superfamily proteins. The PLD superfamily is composed of a large and diverse group of proteins including plant, mammalian and bacterial PLDs, bacterial cardiolipin (CL) synthases, bacterial phosphatidylserine synthases (PSS), eukaryotic phosphatidylglycerophosphate (PGP) synthase, eukaryotic tyrosyl-DNA phosphodiesterase 1 (Tdp1), and some bacterial endonucleases (Nuc and BfiI), among others. PLD enzymes hydrolyze phospholipid phosphodiester bonds to yield phosphatidic acid and a free polar head group. They can also catalyze the transphosphatidylation of phospholipids to acceptor alcohols. The majority of members in this superfamily contain a short conserved sequence motif (H-x-K-x(4)-D, where x represents any amino acid residue), called the HKD signature motif. There are varying expanded forms of this motif in different family members. Some members contain variant HKD motifs. Most PLD enzymes are monomeric proteins with two HKD motif-containing domains. Two HKD motifs from two domains form a single active site. Some PLD enzymes have only one copy of the HKD motif per subunit but form a functionally active dimer, which has a single active site at the dimer interface containing the two HKD motifs from both subunits. Different PLD enzymes may have evolved through domain fusion of a common catalytic core with separate substrate recognition domains. Despite their various catalytic functions and a very broad range of substrate specificities, the diverse group of PLD enzymes can bind to a phosphodiester moiety. Most of them are active as bi-lobed monomers or dimers, and may possess similar core structures for catalytic activity. They are generally thought to 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 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 2784295957   2 GVSVKILVPKDPDLTGffkAMNRQLFSILLDQDIEIYEY------FGFNHEKVMIIDDEIVYFGSYNWDYRSLYLNFENA 75
Cdd:cd00138    40 GVDVRLIIDKPPNAAG---SLSAALLEALLRAGVNVRSYvtpphfFERLHAKVVVIDGEVAYVGSANLSTASAAQNREAG 116

                  ...
gi 2784295957  76 LLV 78
Cdd:cd00138   117 VLV 119

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 2784295957   2 GVSVKILVPKDpDLTGFFKAMNRqlfsiLLDQDIEIYE--YFGFNHEKVMIIDDEIVYFGSYNWDYRSLYLNFENALLVR 79
Cdd:cd09170    50 GVDVRVVLDKS-QAGGKYSALNY-----LANAGIPVRIddNYAIMHNKVMVIDGKTVITGSFNFTASAEKRNAENLLVIR 123

                  .
gi 2784295957  80 S 80
Cdd:cd09170   124 N 124

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 2784295957   2 GVSVKILVPKDPDlTGFFKAMNRQLFSILLDQDIEIYeyFG----FNHEKVMIIDDEIVYFGSYNWDYRSLYLNFENALL 77
Cdd:cd09131    50 GVDVKVVLEDSID-DDEVTEENDNTYRYLKDNGVEVR--FDspsvTTHTKLVVIDGRTVYVGSHNWTYSALDYNHEASVL 126

                  ....*...
gi 2784295957  78 VRSEKVSA 85
Cdd:cd09131   127 IESPEVAD 134

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 2784295957   2 GVSVKILVpkdpDLTGFFkAMNRQLFSILLDQDIEIYEY----------FGFNHEKVMIIDDEIVYFGSYNW------DY 65
Cdd:COG1502    68 GVKVRVLL----DGIGSR-ALNRDFLRRLRAAGVEVRLFnpvrllfrrlNGRNHRKIVVIDGRVAFVGGANItdeylgRD 142

                          90       100
                  ....*....|....*....|....*...
gi 2784295957  66 RSLYLNFENALLVRSEKVSAVMSDFMNR 93
Cdd:COG1502   143 PGFGPWRDTHVRIEGPAVADLQAVFAED 170

Catalytic domain, repeat 2, of vertebrate phospholipases, PLD1 and PLD2, and similar proteins; Catalytic domain, repeat 2, of phospholipase D (PLD, EC 3.1.4.4) found in yeast, plants, and vertebrates, and their bacterial homologs. PLDs are involved in signal transduction, vesicle formation, protein transport, and mitosis by participating in phospholipid metabolism. They hydrolyze the terminal phosphodiester bond of phospholipids resulting in the formation of phosphatidic acid and alcohols. Phosphatidic acid is an essential compound involved in signal transduction. PLDs also catalyze the transphosphatidylation of phospholipids to acceptor alcohols, by which various phospholipids can be synthesized. Both prokaryotic and eukaryotic PLDs have two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. PLDs are active as bi-lobed monomers. Each monomer contains two domains, each of which carries one copy of the HKD motif. Two HKD motifs from two domains form a single active site. PLDs 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 2784295957   2 GVSVKILVPKDPDLTGFFKAMN------RQLFSILLDQDIEIYEYFGFN-------------HEKVMIIDDEIVYFGSYN 62
Cdd:cd09105    49 GLRVVLVLPALPDAVAFGADDGldalalLALLLLADAAPDRVAVFSLAThrrgllggppiyvHSKVVIVDDEWATVGSAN 128

                          90
                  ....*....|....*..
gi 2784295957  63 WDYRSLYLNFENALLVR 79
Cdd:cd09105   129 LNRRSMTWDTELNLAVV 145

Putative catalytic domain of uncharacterized hypothetical proteins closely related to Nuc, , an endonuclease from Salmonella typhimurium; Putative catalytic domain 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 2784295957   2 GVSVKILVPKDPdltgffkaMNRQLFSILLDQDIEIY-------EYFGFNHEKVMIIDDEIVYFGSYNWDYRSLYlNFEN 74
Cdd:cd09174    46 GVNIQIIINDDD--------INKKDVLILDEDSFEIYklpgngsRYGNLMHNKFCVIDFKTVITGSYNWTKNAEY-NFEN 116

                  ..
gi 2784295957  75 AL 76
Cdd:cd09174   117 II 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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2784295957  45 HEKVMIIDDE----IVYFGSYNWDYRSLYLNFENALLVRSEKVSAV-MSDFM 91
Cdd:cd09173   102 HHKFMVIDPFgddpVVITGSHNFSGAANDNNDENLLVIRDPAIADAyAIEFL 153

Putative catalytic domain, repeat 1, of uncharacterized phospholipase D-like proteins; Putative catalytic domain, repeat 1, of uncharacterized phospholipase D (PLD, EC 3.1.4.4)-like proteins. PLD enzymes hydrolyze phospholipid phosphodiester bonds to yield phosphatidic acid and a free polar head group. They can also catalyze transphosphatidylation of phospholipids to acceptor alcohols. Members of this subfamily contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the 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 2784295957   2 GVSVKILVpkDPDLTGFFKAmNRQLFSILLDQDIEIYEY-----FGFNHEKVMIIDDEIVYFGSYNWDYRSLYLNFENAL 76
Cdd:cd09127    47 GVRVRVLL--EGGPVGGISR-AEKLLDYLNEAGVEVRWTngtarYRYTHAKYIVVDDERALVLTENFKPSGFTGTRGFGV 123

                          90
                  ....*....|...
gi 2784295957  77 LVRSEKVSAVMSD 89
Cdd:cd09127   124 VTDDPAVVAEIAD 136

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2784295957   2 GVSVKILV------PKDPDLTGFFKAMNRQLFSIlldqDIEIYEYFGFNHEKVMIIDDEIVYFGSYNWDYRSL 68
Cdd:cd09106    72 GVKIRILQdkpskdKPDEDDLELAALGGAEVRSL----DFTKLIGGGVLHTKFWIVDGKHFYLGSANLDWRSL 140

C-terminal putative phospholipase D-like domain of uncharacterized prokaryotic HKD family nucleases fused to DEAD/DEAH box helicases; C-terminal putative phospholipase D (PLD)-like domain of uncharacterized prokaryotic HKD family nucleases fused to a DEAD/DEAH box helicase domain. All members of this subfamily are uncharacterized. In addition to the helicase-like region, members of this family also contain a PLD-like domain in the C-terminal region, which is characterized by a variant HKD (H-x-K-x(4)-D motif, where x represents any amino acid residue) motif. Due to the lack of key residues related to PLD activity in the variant HKD motif, members of this subfamily are most unlikely to carry PLD activity.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2784295957   1 MGVSVKILVPKDPDLTGFFKAMNRQLFSILLDQDIeiyeyfgfnHEKVMIIDDEIVYFGSYN 62
Cdd:cd09126    49 RGVEVTVVTREPKEYKELIEELRSAGVKVKLKEEI---------HEKFAIIDKKIVWYGSIN 101