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 270265812  95 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDKRVLITGSLNW 174
Cdd:cd09171   25 DVCVFTITCDDLADAILDLHRRGVRVRIITDDDQMEDKGSDIGKLRKAGIPVRTDLSSGHMHHKFAVIDGKILITGSFNW 104

                         90       100       110
                 ....*....|....*....|....*....|..
gi 270265812 175 TTQAIQNNRENVLITEDDEYVRLFLEEFERIW 206
Cdd:cd09171  105 TRQAVTGNQENVLITNDPKLVKPFTEEFEKLW 136

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 270265812  95 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDKRVLITGSLNW 174
Cdd:cd09171   25 DVCVFTITCDDLADAILDLHRRGVRVRIITDDDQMEDKGSDIGKLRKAGIPVRTDLSSGHMHHKFAVIDGKILITGSFNW 104

                         90       100       110
                 ....*....|....*....|....*....|..
gi 270265812 175 TTQAIQNNRENVLITEDDEYVRLFLEEFERIW 206
Cdd:cd09171  105 TRQAVTGNQENVLITNDPKLVKPFTEEFEKLW 136

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 270265812 103 SPQLGRAVQLLHQRGVRVRVVTDC--DYMALNG---SQIGLLRKAGIQVRHDQdPGYMHHKFAIVDKRVLITGSLNWTTQ 177
Cdd:COG1502  229 DRSLLRALIAAARRGVDVRILLPAksDHPLVHWasrSYYEELLEAGVRIYEYE-PGFLHAKVMVVDDEWALVGSANLDPR 307

                         90       100       110
                 ....*....|....*....|....*....|.
gi 270265812 178 AIQNNRENVLITEDDEYVRLFLEEFERIWEQ 208
Cdd:COG1502  308 SLRLNFEVNLVIYDPEFAAQLRARFEEDLAH 338

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 270265812   152 PGYMHHKFAIVDKRVLITGSLNWT 175
Cdd:smart00155   2 DGVLHTKLMIVDDEIAYIGSANLD 25

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 270265812  95 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDKRVLITGSLNW 174
Cdd:cd09171   25 DVCVFTITCDDLADAILDLHRRGVRVRIITDDDQMEDKGSDIGKLRKAGIPVRTDLSSGHMHHKFAVIDGKILITGSFNW 104

                         90       100       110
                 ....*....|....*....|....*....|..
gi 270265812 175 TTQAIQNNRENVLITEDDEYVRLFLEEFERIW 206
Cdd:cd09171  105 TRQAVTGNQENVLITNDPKLVKPFTEEFEKLW 136

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 270265812  99 FAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDKRVLITGSLNWTTQA 178
Cdd:cd09170   32 YSFTSPPIARALIAAKKRGVDVRVVLDKSQAGGKYSALNYLANAGIPVRIDDNYAIMHNKVMVIDGKTVITGSFNFTASA 111

                         90       100       110
                 ....*....|....*....|....*....|.
gi 270265812 179 IQNNRENVLITEDD-EYVRLFLEEFERIWEQ 208
Cdd:cd09170  112 EKRNAENLLVIRNPpELAQQYLQEWQRRWAQ 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 270265812 103 SPQLGRAVQLLHQRGVRVRVVTDC--DYMALNG---SQIGLLRKAGIQVRHDQdPGYMHHKFAIVDKRVLITGSLNWTTQ 177
Cdd:COG1502  229 DRSLLRALIAAARRGVDVRILLPAksDHPLVHWasrSYYEELLEAGVRIYEYE-PGFLHAKVMVVDDEWALVGSANLDPR 307

                         90       100       110
                 ....*....|....*....|....*....|.
gi 270265812 178 AIQNNRENVLITEDDEYVRLFLEEFERIWEQ 208
Cdd:COG1502  308 SLRLNFEVNLVIYDPEFAAQLRARFEEDLAH 338

nuclease NucT; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 270265812  95 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNG-SQIGLLRKA---------GIQVRHDQDPGYMHHKFAIVDK 164
Cdd:PRK13912  50 KIAIYSFTHKDIAKALKSAAKRGVKISIIYDYESNHNNDqSTIGYLDKYpnikvcllkGLKAKNGKYYGIMHQKVAIIDD 129

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 270265812 165 RVLITGSLNWTTQAIQNNRENVLITEDDEYVRLFLEEFERIWEQFNP 211
Cdd:PRK13912 130 KIVVLGSANWSKNAFENNYEVLLITDDTETILKAKEYFQKMLGSCVG 176

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 270265812  95 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQI---GLLRKAGIQ----------VRHDQDP--GYMHHKF 159
Cdd:cd09173   26 LFALFDFSDGALLDALLAAADAGLFVRGLVDKRFGGRYYSAAadmGGIDPVYPAalapdepekfVGEPLLGvgDKLHHKF 105

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 270265812 160 AIVD----KRVLITGSLNWTTQAIQNNRENVLITEDDEYVRLFLEEFERIWEQF 209
Cdd:cd09173  106 MVIDpfgdDPVVITGSHNFSGAANDNNDENLLVIRDPAIADAYAIEFLRLYDHY 159

Putative catalytic domain, repeat 1, of uncharacterized hypothetical proteins similar to Nuc, an endonuclease from Salmonella typhimurium; Putative catalytic domain, repeat 1, 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 270265812  95 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDC----DYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDK----RV 166
Cdd:cd09172   26 RLAIYELDDPEIIDALKAAKDRGVRVRIILDDssvtGDPTEESAAATLSKGPGALVKRRHSSGLMHNKFLVVDRkdgpNR 105

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 270265812 167 LITGSLNWTTQAI--QNNreNVLITEDDEyvrlFLEEFERIWEQF 209
Cdd:cd09172  106 VLTGSTNFTTSGLygQSN--NVLIFRNPA----FAAAYLAYWNTL 144

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 270265812  95 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVtdcdymaLNGS----------QIGLLRKAGIQVRHDQDPG---YMHHKFAI 161
Cdd:cd09127   25 LLKMYEFTDPALEKALAAAAKRGVRVRVL-------LEGGpvggisraekLLDYLNEAGVEVRWTNGTAryrYTHAKYIV 97

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 270265812 162 VD-KRVLITgSLNWTTQAIQNNRENVLITEDDEYVRLFLEEFE 203
Cdd:cd09127   98 VDdERALVL-TENFKPSGFTGTRGFGVVTDDPAVVAEIADVFD 139

N-terminal putative catalytic domain of uncharacterized prokaryotic and archeal HKD family nucleases fused to a DEAD/DEAH box helicase domain; N-terminal putative catalytic domain of uncharacterized prokaryotic and archeal HKD family nucleases fused to a DEAD/DEAH box helicase domain. All members of this subfamily are uncharacterized. Other characterized members of the superfamily that have a related domain architecture ( containing a DEAD/DEAH box helicase domain), include the DNA/RNA helicase superfamily II (SF2) and Res-subunit of type III restriction endonucleases. In addition to the helicase-like region, members of this subfamily also contain one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in the N-terminal putative catalytic domain. The HKD motif characterizes the phospholipase D (PLD, EC 3.1.4.4) superfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 270265812 113 LHQRGVRVRVVTDcDYmaLNGSQIGLLRK----AGIQVR-HDQDPGYmHHKFAIVDKR---VLITGSLNWTTQAIQNNRE 184
Cdd:cd09204   39 LEERGIKGRILTS-TY--LNFNEPKAFREllklPNIEVRiYDEDEGF-HAKGYIFEHEdyyTIIVGSSNLTQSALKSNYE 114

                         90       100
                 ....*....|....*....|....*
gi 270265812 185 -NVLIT--EDDEYVRLFLEEFERIW 206
Cdd:cd09204  115 wNLKVSstENGDLVEQVLEEFERLW 139

Sugar-specific transcriptional regulator TrmB [Transcription];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 270265812 104 PQLGRAVQLLHQRGVRVRVVTDCDYMALngsqIGLLRKAGIQVRHDQDPgymHHKFAIVDKRVLITGSLNwttqaiQNNR 183
Cdd:COG1378  145 EELEEALEEALERGVKVRVLVSPEVLEV----PERLEEEGEEVRVLPGL---PGRLLIVDDKEALISVSE------PDGE 211

                         90       100
                 ....*....|....*....|....*
gi 270265812 184 ENVLITEDDEYVRLFLEEFERIWEQ 208
Cdd:COG1378  212 ETAIWIEDPELAALLRELFETLWEK 236

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 270265812  95 DLCLFAFSSPQLGRAV-QLL---HQRGVRVRVVTDcDY--MALNGSQIGLLRKAGIQVR------HDQDPGYM----HHK 158
Cdd:cd09110   22 HLEYYIFRDDEIGRRFrDALiekARRGVEVRLLYD-GFgsLGLSRRFLRELREAGVEVRafnplsFPLFLLRLnyrnHRK 100

                         90
                 ....*....|....*
gi 270265812 159 FAIVDKRVLITGSLN 173
Cdd:cd09110  101 ILVIDGKIAFVGGFN 115

Putative catalytic domain, repeat 2, of uncharacterized phospholipase D-like proteins; Putative catalytic domain, repeat 2, 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 270265812 114 HQRGVRVRVVTDCDYMALNGSQIGL-----------LRKAGIQVRHDQDPGYMHH-KFAIVDKR---VLITGSLNWTTQA 178
Cdd:cd09130   43 ANRGVDVRLILDPNKDAFGREKNGIpnrpvaaelmkKTKGKIQIRWYNTGGEQFHtKLLLIKKKgqaIIIGGSANFTRRN 122

                         90       100       110
                 ....*....|....*....|....*....|...
gi 270265812 179 IQN-NRE-NVLIT--EDDEYVRLFLEEFERIWE 207
Cdd:cd09130  123 LRDyNLEtDLKILapNDSPVSKDVDAYFDRLWN 155

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 270265812   152 PGYMHHKFAIVDKRVLITGSLNWT 175
Cdd:smart00155   2 DGVLHTKLMIVDDEIAYIGSANLD 25

Putative catalytic domain, repeat 2, of vertebrate phospholipases, PLD3, PLD4 and PLD5, viral envelope proteins K4 and p37, and similar proteins; Putative catalytic domain, repeat 2, 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 270265812 116 RGVRVRVV------TDCDYMALNGS---QIGLLRKAGIQVRHDQDPGY----------MHHKFAIVDKRVLITGSlNWTT 176
Cdd:cd09107   66 RGVKVRLLvsnwkhTDPSMDAFLKSlqlLKSGVGNGDIEVKIFTVPGDqstkipfarvNHAKYMVTDERAYIGTS-NWSG 144

                         90       100       110
                 ....*....|....*....|....*....|.
gi 270265812 177 QAIQNNReNV-LITEDDEYVRLFLEEFERIW 206
Cdd:cd09107  145 DYFYNTA-GVsLVINDPAIVQQLKDVFERDW 174

N-terminal putative catalytic domain of uncharacterized HKD family nucleases fused to putative helicases from the Snf2-like family; N-terminal putative catalytic domain of uncharacterized archaeal and prokaryotic HKD family nucleases fused to putative helicases from the Snf2-like family, which belong to the DNA/RNA helicase superfamily II (SF2). Although Snf2-like family enzymes do not possess helicase activity, they contain a helicase-like region, where seven helicase-related sequence motifs are found, similar to those in DEAD/DEAH box helicases, which represent the biggest family within the SF2 superfamily. In addition to the helicase-like region, members of this family also contain an N-terminal putative catalytic domain with one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), and have been classified as members of the phospholipase D (PLD, EC 3.1.4.4) superfamily.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 270265812 136 IGLLRKAGIQVR-HDQDP----GY-MHHKFAIVDKRVLITGSLNWTTQAIQNNRE-NVLITEDDEYvRLFLEEFERIWE 207
Cdd:cd09178   55 IELIKEGKVEIRvYTKGFlhakAYlFDGPDNDNGPGTAIVGSSNFTKAGLTGNLElNVEVKDRDDV-EELKEWFEELWE 132

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 270265812  95 DLCLFAFSSPQLGRAV-QLLHQR---GVRVRVVTDcDYMALNGSQIGL--LRKAGIQVR------HDQDPGYM----HHK 158
Cdd:cd09156   22 DVCTFILGDDATGRRViDALARKareGVEVRLLLD-ALGSFFLSRRALkkLRAAGGKVAffmpvfRLPFRGRTnlrnHRK 100

                         90
                 ....*....|....*
gi 270265812 159 FAIVDKRVLITGSLN 173
Cdd:cd09156  101 IAIADGSTAISGGMN 115

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 270265812 102 SSPQLGRA-----VQLLH---QRGVRVRVVTD--CDYMALngsqIGLLRKAGIQVRHDQDpgyMHHKFAIVDKRVLITGS 171
Cdd:cd09126   27 SSPYVSQKritklINLLKeaqERGVEVTVVTRepKEYKEL----IEELRSAGVKVKLKEE---IHEKFAIIDKKIVWYGS 99

                 ..
gi 270265812 172 LN 173
Cdd:cd09126  100 IN 101

N-terminal putative catalytic domain of uncharacterized prokaryotic and archeal HKD family nucleases fused to a DEAD/DEAH box helicase domain; N-terminal putative catalytic domain of uncharacterized prokaryotic and archeal HKD family nucleases fused to a DEAD/DEAH box helicase domain. All members of this subfamily are uncharacterized. Other characterized members of the superfamily that have a related domain architecture ( containing a DEAD/DEAH box helicase domain), include the DNA/RNA helicase superfamily II (SF2) and Res-subunit of type III restriction endonucleases. In addition to the helicase-like region, members of this subfamily also contain one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in the N-terminal putative catalytic domain. The HKD motif characterizes the phospholipase D (PLD, EC 3.1.4.4) superfamily. A few family members contain additional domains, like a C-terminal peptidase S24-like domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 270265812 115 QRGVRVRVVTDcDYM------ALngSQIGLLRKAGIQVR-HDQDPGYMHHK---FAIVDKR-VLITGSLNWTTQAIQNNR 183
Cdd:cd09205   41 SRGARIRILTG-DYLditqpeAL--RRLLDLLGDGIEIRvFESGGRSFHPKaylFEREDGGgAAFVGSSNLSKSALTDGI 117

                         90       100
                 ....*....|....*....|....*.
gi 270265812 184 E-NVLI--TEDDEYVRLFLEEFERIW 206
Cdd:cd09205  118 EwNLRIdrSADPDAFDEAKEAFEKLF 143