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 1551910140 203 FIASAPQQLCTMERTNDLTALLSCIGNASKFVYVSVMNFIPIIYSkAGNILFWPYIEDELRRAAIDRQVSVKLLISCWQR 282
Cdd:cd09107     1 FLSSSPPELCPPGRTDDLDALLSTIDSAKKFIDISVMDYVPLSRY-ADPRKYWPVIDNALRRAAVDRGVKVRLLVSNWKH 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 283 SSFIMRNFLRSIAMLKS--KNIDIEVKLFIVPDADP-PIPYSRVNHAKYMVTDKTAYIGTSNWTGNYFTDTCGASINITP 359
Cdd:cd09107    80 TDPSMDAFLKSLQLLKSgvGNGDIEVKIFTVPGDQStKIPFARVNHAKYMVTDERAYIGTSNWSGDYFYNTAGVSLVIND 159

                         170
                  ....*....|....*....
gi 1551910140 360 DDglgLRQQLEDIFMRDWN 378
Cdd:cd09107   160 PA---IVQQLKDVFERDWN 175

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 1551910140  27 TFNVWREILSNTTKTLDISSFYWSlSDEVGTNFgttiLNEIVQLPKRGVRVRV---AVNKSNKPLKDVETLQMAGVEVRY 103
Cdd:COG1502    26 AFAALLEAIEAARRSIDLEYYIFD-DDEVGRRL----ADALIAAARRGVKVRVlldGIGSRALNRDFLRRLRAAGVEVRL 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 104 ID----ITNILGGVLHTKFWISDNTHIYLGSANMDWRSLTQVKELGiaifNNRNL--------AADLTQIFEVYWylgvn 171
Cdd:COG1502   101 FNpvrlLFRRLNGRNHRKIVVIDGRVAFVGGANITDEYLGRDPGFG----PWRDThvriegpaVADLQAVFAEDW----- 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 172 nlpynwknfypaYYNTDHPLSMNVSGVPHSV-FIASAPqqlcTMERTNDLTALLSCIGNASKFVYVSVMNFIPiiySKAg 250
Cdd:COG1502   172 ------------NFATGEALPFPEPAGDVRVqVVPSGP----DSPRETIERALLAAIASARRRIYIETPYFVP---DRS- 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 251 nilfwpyIEDELRRAAiDRQVSVKLLISCWQRSSFIMRNFLRSIAMLKSKNidieVKLFIVPDadppipysRVNHAKYMV 330
Cdd:COG1502   232 -------LLRALIAAA-RRGVDVRILLPAKSDHPLVHWASRSYYEELLEAG----VRIYEYEP--------GFLHAKVMV 291

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1551910140 331 TD-KTAYIGTSNWTGNYFT-DT-CGASInitpdDGLGLRQQLEDIFMRDWNSkySYEL 385
Cdd:COG1502   292 VDdEWALVGSANLDPRSLRlNFeVNLVI-----YDPEFAAQLRARFEEDLAH--SREV 342

cardiolipin synthase; This model is based on experimentally characterized bacterial cardiolipin synthases (cls) from E. coli, Staphylococcus aureus (two), and Bacillus pseudofirmus OF4. This model describes just one of several homologous but non-orthologous forms of cls. The cutoff score is set arbitrarily high to avoid false-positives. Note that there are two enzymatic activites called cardiolipin synthase. This model represents type 1, which does not rely on a CDP-linked donor, but instead does a reversible transfer of a phosphatidyl group from one phosphatidylglycerol molecule to another.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140  63 ILNEIVQLPKRGVRVRVAV-NKSNKPL------KDVETLQMAGVEVRYIDitnilGGVLHTKFWISDNTHIYLGSANMDW 135
Cdd:TIGR04265 347 LLHAIKIAALSGVDVSIMIpNKPDHPLvfwasrSNFTELLAAGVKIYQYE-----NGFLHSKSVLVDDEIASVGTANMDM 421

                          90       100       110
                  ....*....|....*....|....*....|
gi 1551910140 136 RSLTQVKELGIAIFnNRNLAADLTQIFEVY 165
Cdd:TIGR04265 422 RSFWLNFEVNAFIY-DKGFAKDLAAAYDDD 450

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 1551910140 203 FIASAPQQLCTMERTNDLTALLSCIGNASKFVYVSVMNFIPIIYSkAGNILFWPYIEDELRRAAIDRQVSVKLLISCWQR 282
Cdd:cd09107     1 FLSSSPPELCPPGRTDDLDALLSTIDSAKKFIDISVMDYVPLSRY-ADPRKYWPVIDNALRRAAVDRGVKVRLLVSNWKH 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 283 SSFIMRNFLRSIAMLKS--KNIDIEVKLFIVPDADP-PIPYSRVNHAKYMVTDKTAYIGTSNWTGNYFTDTCGASINITP 359
Cdd:cd09107    80 TDPSMDAFLKSLQLLKSgvGNGDIEVKIFTVPGDQStKIPFARVNHAKYMVTDERAYIGTSNWSGDYFYNTAGVSLVIND 159

                         170
                  ....*....|....*....
gi 1551910140 360 DDglgLRQQLEDIFMRDWN 378
Cdd:cd09107   160 PA---IVQQLKDVFERDWN 175

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 1551910140  10 ITETIPIGMQF--DKVYLSTFNVWREILSNTTKTLDISSFYWSLSDEV-----GTNFGTTILNEIVQLPKRGVRVRVAVN 82
Cdd:cd09106     1 LVESIPEGLTFlsSSSHLSTFEAWMELISSAKKSIDIASFYWNLRGTDtnpdsSAQEGEDIFNALLEAAKRGVKIRILQD 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1551910140  83 KSNKPLKDVETLQMA---GVEVRYIDITN-ILGGVLHTKFWISDNTHIYLGSANMDWRSLTQVKELGIAIFN 150
Cdd:cd09106    81 KPSKDKPDEDDLELAalgGAEVRSLDFTKlIGGGVLHTKFWIVDGKHFYLGSANLDWRSLTQVKELGVYIYN 152

Putative catalytic domain, repeat 2, of vertebrate phospholipase PLD4; Putative catalytic domain, repeat 2, of vertebrate phospholipases D4 (PLD4, EC 3.1.4.4), homologs of the vaccinia virus protein K4 which is encoded by the HindIII K4L gene. Due to the presence of two copies of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), PLD4 has been assigned to PLD superfamily although no catalytic activity has been detected to date. Unlike PLD1 and PLD2, PLD4 does not contain Phox (PX) and Pleckstrin homology (PH) domains but has a putative transmembrane domain. Like other vertebrate homologs of protein K4, PLD4 might be associated with Golgi membranes and alter their lipid content by selectively hydrolyze phosphatidylcholine (PC) into corresponding phosphatidic acid, which is thought to be involved in the regulation of lipid movement.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 203 FIASAPQQLCTMERTNDLTALLSCIGNASKFVYVSVMNFIPIIYSkAGNILFWPYIEDELRRAAIDRQVSVKLLISCWQR 282
Cdd:cd09148     1 YLSASPPALCPTGRTSDLQAILSVISQAQEFIYISVMEYFPTCRF-CHPKRYWSVLDNALRAAAFDRRVLIRLLISCGRH 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 283 SSFIMRNFLRSIAMLKSK--NIDIEVKLFIVPDADPP-IPYSRVNHAKYMVTDKTAYIGTSNWTGNYFTDTCGASINIT- 358
Cdd:cd09148    80 SDPDMFPFLRSLNALSNPplSISVHVKLFIVPVGNQTnIPYSRVNHNKFMVTDKAAYIGTSNWSEDYFLNTAGVGLVILq 159

                         170       180
                  ....*....|....*....|....*...
gi 1551910140 359 ----PDDGLGLRQQLEDIFMRDWNSKYS 382
Cdd:cd09148   160 spgaNEEMLPVQEQLRSLFERDWSSPYA 187

Putative catalytic domain, repeat 1, of vertebrate phospholipase PLD4; Putative catalytic domain, repeat 1, of vertebrate phospholipases D4 (PLD4, EC 3.1.4.4), homologs of the vaccinia virus protein K4 which is encoded by the HindIII K4L gene. Due to the presence of two copies of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), PLD4 has been assigned to PLD superfamily although no catalytic activity has been detected to date. Unlike PLD1 and PLD2, PLD4 does not contain Phox (PX) and Pleckstrin homology (PH) domains but has a putative transmembrane domain. Like other vertebrate homologs of protein K4, PLD4 might be associated with Golgi membranes and alter their lipid content by selectively hydrolyze phosphatidylcholine (PC) into corresponding phosphatidic acid, which is thought to be involved in the regulation of lipid movement.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140  10 ITETIPIGMQFD---KVYLSTFNVWREILSNTTKTLDISSFYWSLSDE-VGTN-----FGTTILNEIVQLPKRGVRVRVA 80
Cdd:cd09145     1 LVESIPEDLTYEgnsTFALPLQKAWTKLLDMAQEQVHVASYYWSLTGEdIGVNdssslPGEDILKELAELLSRNVSVRAA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140  81 VnkSNKPLK----DVETLQMAGVEVRYIDITNILGGVLHTKFWISDNTHIYLGSANMDWRSLTQVKELGIAIFNNRNLAA 156
Cdd:cd09145    81 A--SIPTLAanstDLKILRQKGAHVRKVNFGRLTGGVLHSKFWIIDKKHIYVGSANMDWRSLTQVKELGAVIYNCSSLAK 158

                         170
                  ....*....|..
gi 1551910140 157 DLTQIFEVYWYL 168
Cdd:cd09145   159 DLHKTFQTYWVL 170

PLD-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 137 SLTQVKELGIAIFNNRNLAADLTQIFEVYWYLGVNN-LPYNWKNFYPAYYNTDHPLSMNVSGVPHSVFIASAPQQLCTME 215
Cdd:pfam13918   1 SLGQIKELGLVFTNCKCLALDLMNIFALFSSLIFENkVPFTWSKRLCCAVDNEKALNFHLNESGGGAFFSDSPELFCGFN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 216 RTNDLTALLSCIGNASKFVYVSVMNFIPIIySKAGNILFWPYIEDELRRAAIDRQVSVKLLISCWQRSSFIMRNFLRSIA 295
Cdd:pfam13918  81 RSFDEDAILHRIDDAKLSIDIALLDMLPII-KHAGAREYWPDIDDAILEAAILRGVKVRLIISEWKEADPLSFNAARSLD 159

                         170
                  ....*....|....*....
gi 1551910140 296 MLKSK--NIDIEVKLFIVP 312
Cdd:pfam13918 160 AFCTEiaNCDLKVKFFDLE 178

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 1551910140  27 TFNVWREILSNTTKTLDISSFYWSlSDEVGTNFgttiLNEIVQLPKRGVRVRV---AVNKSNKPLKDVETLQMAGVEVRY 103
Cdd:COG1502    26 AFAALLEAIEAARRSIDLEYYIFD-DDEVGRRL----ADALIAAARRGVKVRVlldGIGSRALNRDFLRRLRAAGVEVRL 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 104 ID----ITNILGGVLHTKFWISDNTHIYLGSANMDWRSLTQVKELGiaifNNRNL--------AADLTQIFEVYWylgvn 171
Cdd:COG1502   101 FNpvrlLFRRLNGRNHRKIVVIDGRVAFVGGANITDEYLGRDPGFG----PWRDThvriegpaVADLQAVFAEDW----- 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 172 nlpynwknfypaYYNTDHPLSMNVSGVPHSV-FIASAPqqlcTMERTNDLTALLSCIGNASKFVYVSVMNFIPiiySKAg 250
Cdd:COG1502   172 ------------NFATGEALPFPEPAGDVRVqVVPSGP----DSPRETIERALLAAIASARRRIYIETPYFVP---DRS- 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 251 nilfwpyIEDELRRAAiDRQVSVKLLISCWQRSSFIMRNFLRSIAMLKSKNidieVKLFIVPDadppipysRVNHAKYMV 330
Cdd:COG1502   232 -------LLRALIAAA-RRGVDVRILLPAKSDHPLVHWASRSYYEELLEAG----VRIYEYEP--------GFLHAKVMV 291

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1551910140 331 TD-KTAYIGTSNWTGNYFT-DT-CGASInitpdDGLGLRQQLEDIFMRDWNSkySYEL 385
Cdd:COG1502   292 VDdEWALVGSANLDPRSLRlNFeVNLVI-----YDPEFAAQLRARFEEDLAH--SREV 342

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 1551910140  30 VWREILSNTTKTLDISSFYWSlsdevgTNFGTTILNEIVQLPKRGVRVRVAVNKSNKPL-----KDVETLQMAGVEVRYI 104
Cdd:cd00138     2 ALLELLKNAKESIFIATPNFS------FNSADRLLKALLAAAERGVDVRLIIDKPPNAAgslsaALLEALLRAGVNVRSY 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1551910140 105 DITNILGGVLHTKFWISDNTHIYLGSANMDWRSLTQVKELGIAI 148
Cdd:cd00138    76 VTPPHFFERLHAKVVVIDGEVAYVGSANLSTASAAQNREAGVLV 119

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 1551910140  63 ILNEIVQLPKRGVRVRV----AVNKSNKPLKDVETLQMAGVEVRYIDITNIlggVLHTKFWISDNTHIYLGSANMDWRSL 138
Cdd:cd09128    39 ILDALVDAAKRGVDVRVllpsAWSAEDERQARLRALEGAGVPVRLLKDKFL---KIHAKGIVVDGKTALVGSENWSANSL 115

                          90       100
                  ....*....|....*....|....*...
gi 1551910140 139 TQVKELGIaIFNNRNLAADLTQIFEVYW 166
Cdd:cd09128   116 DRNREVGL-IFDDPEVAAYLQAVFESDW 142

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 1551910140 222 ALLSCIGNASKFVYVSVMNFipiiyskagNILFWPYIEDELRRAAiDRQVSVKLLISCWQRSSFIMRNflrsIAMLKSKN 301
Cdd:cd00138     2 ALLELLKNAKESIFIATPNF---------SFNSADRLLKALLAAA-ERGVDVRLIIDKPPNAAGSLSA----ALLEALLR 67

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1551910140 302 IDIEVKLFivpdaDPPIPYSRVNHAKYMVTD-KTAYIGTSNWTGNYF 347
Cdd:cd00138    68 AGVNVRSY-----VTPPHFFERLHAKVVVIDgEVAYVGSANLSTASA 109

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 1551910140  111 GGVLHTKFWISDNTHIYLGSANMDWRS 137
Cdd:smart00155   2 DGVLHTKLMIVDDEIAYIGSANLDGRS 28

PLD-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140 223 LLSCIGNASKFVYVSVMNFIPIiyskagnilfwPYIEDELRRAAiDRQVSVKLLISCWQRSSFIMRnfLRSIAMLKSK-N 301
Cdd:pfam13091   1 LIDLINSAKKSIDIATYYFVPD-----------REIIDALIAAA-KRGVDVRIILDSNKDDAGGPK--KASLKELRSLlR 66

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1551910140 302 IDIEVKLFIvpdadppiPYSRVNHAKYMVTD-KTAYIGTSNWTGNYFTDTCGASINItpdDGLGLRQQLEDIFMRDW 377
Cdd:pfam13091  67 AGVEIREYQ--------SFLRSMHAKFYIIDgKTVIVGSANLTRRALRLNLENNVVI---KDPELAQELEKEFDRLW 132

Phospholipase D Active site motif; Phosphatidylcholine-hydrolysing 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 homolog 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, and/or asparagine residues which may contribute to the active site. aspartic acid. An E. coli endonuclease (nuc) and similar proteins appear to be PLD homologs 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 1551910140 110 LGGVLHTKFWISDNTHIYLGSANMDWRS 137
Cdd:pfam00614   1 YDGRLHRKIVVVDDELAYIGGANLDGRS 28

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 1551910140  62 TILNEIVQLPKRGVRVRVAVNKSNKPLKDVET-------LQMAGVEVRYiDITNIlggVLHTKFWISDNTHIYLGSANMD 134
Cdd:cd09131    38 TLLEALIDAHKRGVDVKVVLEDSIDDDEVTEEndntyryLKDNGVEVRF-DSPSV---TTHTKLVVIDGRTVYVGSHNWT 113

                          90       100
                  ....*....|....*....|....*...
gi 1551910140 135 WRSLTQVKELGIAIfNNRNLAADLTQIF 162
Cdd:cd09131   114 YSALDYNHEASVLI-ESPEVADFAINYF 140

cardiolipin synthase; This model is based on experimentally characterized bacterial cardiolipin synthases (cls) from E. coli, Staphylococcus aureus (two), and Bacillus pseudofirmus OF4. This model describes just one of several homologous but non-orthologous forms of cls. The cutoff score is set arbitrarily high to avoid false-positives. Note that there are two enzymatic activites called cardiolipin synthase. This model represents type 1, which does not rely on a CDP-linked donor, but instead does a reversible transfer of a phosphatidyl group from one phosphatidylglycerol molecule to another.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1551910140  63 ILNEIVQLPKRGVRVRVAV-NKSNKPL------KDVETLQMAGVEVRYIDitnilGGVLHTKFWISDNTHIYLGSANMDW 135
Cdd:TIGR04265 347 LLHAIKIAALSGVDVSIMIpNKPDHPLvfwasrSNFTELLAAGVKIYQYE-----NGFLHSKSVLVDDEIASVGTANMDM 421

                          90       100       110
                  ....*....|....*....|....*....|
gi 1551910140 136 RSLTQVKELGIAIFnNRNLAADLTQIFEVY 165
Cdd:TIGR04265 422 RSFWLNFEVNAFIY-DKGFAKDLAAAYDDD 450

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 1551910140  72 KRGVRVRVAV-NKSNKPLKD------VETLQMAGVEVRYIDitnilGGVLHTKFWISDNTHIYLGSANMDWRSLTQVKEL 144
Cdd:cd09112    49 LSGVDVRIMIpGKPDHKLVYwasrsyFEELLKAGVKIYEYN-----KGFLHSKTLIVDDEIASVGTANLDIRSFELNFEV 123

                          90
                  ....*....|....*....
gi 1551910140 145 GIAIFnNRNLAADLTQIFE 163
Cdd:cd09112   124 NAVIY-DKEVAKKLEEIFE 141

Putative catalytic domain, repeat 2, of Streptococcus mutans uncharacterized protein SMU_988 and similar proteins; Putative catalytic domain, repeat 2, of Streptococcus mutans uncharacterized protein SMU_988 and similar proteins. Although SMU_988 and similar proteins have not been functionally characterized, members in this subfamily show high sequence homology 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 1551910140  29 NVWREILSNTTKTLDISSFYWSLSDEvgtnfgttILNEIVQLPKRGVRVRV------------AVNKSNKPlkdveTLQM 96
Cdd:cd09160    14 NVYLDLINQAKDYVYITTPYLILDDE--------MLDALCLAAKRGVDVRIitphipdkkyvfLVTRSNYP-----ELLE 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1551910140  97 AGVEV-RYiditniLGGVLHTKFWISDNTHIYLGSANMDWRSLTQVKELGIAIFNN---RNLAADLTQIFEV 164
Cdd:cd09160    81 AGVKIyEY------TPGFIHAKTFVSDDKAAVVGTINLDYRSLYLHFECGVYMYDTpviSDIKEDFEETLAQ 146

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 1551910140 256 PYIEDELRrAAIDRQVSVKLLIScwQRSSFIMRNFLRSIAMLKSKNIDievklfiVPDADPPIPYsRVNHAKYMVTD-KT 334
Cdd:cd09127    34 PALEKALA-AAAKRGVRVRVLLE--GGPVGGISRAEKLLDYLNEAGVE-------VRWTNGTARY-RYTHAKYIVVDdER 102

                          90
                  ....*....|....*...
gi 1551910140 335 AYIGTSNWTGNYFTDTCG 352
Cdd:cd09127   103 ALVLTENFKPSGFTGTRG 120

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1551910140  63 ILNEIVQLPKRGVRVRVAVNKSNKPLKD--VETLQMAGVEVRyidiTNILGGVLHTKFWISDNTHIYLGSAN 132
Cdd:cd09170    39 IARALIAAKKRGVDVRVVLDKSQAGGKYsaLNYLANAGIPVR----IDDNYAIMHNKVMVIDGKTVITGSFN 106

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 1551910140  73 RGVRVRVAVNK----------SNKPLKDVETL-QMAGVEVRYIDI-----TNI-LGGVLHTKFWISDnTHIYLGSANMDW 135
Cdd:cd09107    66 RGVKVRLLVSNwkhtdpsmdaFLKSLQLLKSGvGNGDIEVKIFTVpgdqsTKIpFARVNHAKYMVTD-ERAYIGTSNWSG 144

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1551910140 136 RSLTQVKELGIaIFNNRNLAADLTQIFEVYWY 167
Cdd:cd09107   145 DYFYNTAGVSL-VINDPAIVQQLKDVFERDWN 175

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 1551910140 217 TNDLTALLSCIGNA--SKFVYVSVMNFIPIIyskagnilfwpyiEDELRRAAiDRQVSVKLLIScwqRSSFIMRNFLRSI 294
Cdd:cd09128     9 DNAREALLALIDSAeeSLLIQNEEMGDDAPI-------------LDALVDAA-KRGVDVRVLLP---SAWSAEDERQARL 71