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 119576122 105 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDKRVLITGSLNW 184
Cdd:cd09171   25 DVCVFTITCDDLADAILDLHRRGVRVRIITDDDQMEDKGSDIGKLRKAGIPVRTDLSSGHMHHKFAVIDGKILITGSFNW 104

                         90       100       110
                 ....*....|....*....|....*....|..
gi 119576122 185 TTQAIQNNRENVLITEDDEYVRLFLEEFERIW 216
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 119576122 105 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDKRVLITGSLNW 184
Cdd:cd09171   25 DVCVFTITCDDLADAILDLHRRGVRVRIITDDDQMEDKGSDIGKLRKAGIPVRTDLSSGHMHHKFAVIDGKILITGSFNW 104

                         90       100       110
                 ....*....|....*....|....*....|..
gi 119576122 185 TTQAIQNNRENVLITEDDEYVRLFLEEFERIW 216
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 119576122 113 SPQLGRAVQLLHQRGVRVRVVTDC--DYMALNG---SQIGLLRKAGIQVRHDQdPGYMHHKFAIVDKRVLITGSLNWTTQ 187
Cdd:COG1502  229 DRSLLRALIAAARRGVDVRILLPAksDHPLVHWasrSYYEELLEAGVRIYEYE-PGFLHAKVMVVDDEWALVGSANLDPR 307

                         90       100       110
                 ....*....|....*....|....*....|.
gi 119576122 188 AIQNNRENVLITEDDEYVRLFLEEFERIWEQ 218
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 119576122   162 PGYMHHKFAIVDKRVLITGSLNWT 185
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 119576122 105 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDKRVLITGSLNW 184
Cdd:cd09171   25 DVCVFTITCDDLADAILDLHRRGVRVRIITDDDQMEDKGSDIGKLRKAGIPVRTDLSSGHMHHKFAVIDGKILITGSFNW 104

                         90       100       110
                 ....*....|....*....|....*....|..
gi 119576122 185 TTQAIQNNRENVLITEDDEYVRLFLEEFERIW 216
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 119576122 109 FAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDKRVLITGSLNWTTQA 188
Cdd:cd09170   32 YSFTSPPIARALIAAKKRGVDVRVVLDKSQAGGKYSALNYLANAGIPVRIDDNYAIMHNKVMVIDGKTVITGSFNFTASA 111

                         90       100       110
                 ....*....|....*....|....*....|.
gi 119576122 189 IQNNRENVLITEDD-EYVRLFLEEFERIWEQ 218
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 119576122 113 SPQLGRAVQLLHQRGVRVRVVTDC--DYMALNG---SQIGLLRKAGIQVRHDQdPGYMHHKFAIVDKRVLITGSLNWTTQ 187
Cdd:COG1502  229 DRSLLRALIAAARRGVDVRILLPAksDHPLVHWasrSYYEELLEAGVRIYEYE-PGFLHAKVMVVDDEWALVGSANLDPR 307

                         90       100       110
                 ....*....|....*....|....*....|.
gi 119576122 188 AIQNNRENVLITEDDEYVRLFLEEFERIWEQ 218
Cdd:COG1502  308 SLRLNFEVNLVIYDPEFAAQLRARFEEDLAH 338

nuclease NucT; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119576122 105 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNG-SQIGLLRKA---------GIQVRHDQDPGYMHHKFAIVDK 174
Cdd:PRK13912  50 KIAIYSFTHKDIAKALKSAAKRGVKISIIYDYESNHNNDqSTIGYLDKYpnikvcllkGLKAKNGKYYGIMHQKVAIIDD 129

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 119576122 175 RVLITGSLNWTTQAIQNNRENVLITEDDEYVRLFLEEFERIWEQFNP 221
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 119576122 105 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQI---GLLRKAGIQ----------VRHDQDP--GYMHHKF 169
Cdd:cd09173   26 LFALFDFSDGALLDALLAAADAGLFVRGLVDKRFGGRYYSAAadmGGIDPVYPAalapdepekfVGEPLLGvgDKLHHKF 105

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 119576122 170 AIVD----KRVLITGSLNWTTQAIQNNRENVLITEDDEYVRLFLEEFERIWEQF 219
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 119576122 105 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDC----DYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDK----RV 176
Cdd:cd09172   26 RLAIYELDDPEIIDALKAAKDRGVRVRIILDDssvtGDPTEESAAATLSKGPGALVKRRHSSGLMHNKFLVVDRkdgpNR 105

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 119576122 177 LITGSLNWTTQAI--QNNreNVLITEDDEyvrlFLEEFERIWEQF 219
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 119576122 105 DLCLFAFSSPQLGRAVQLLHQRGVRVRVVtdcdymaLNGS----------QIGLLRKAGIQVRHDQDPG---YMHHKFAI 171
Cdd:cd09127   25 LLKMYEFTDPALEKALAAAAKRGVRVRVL-------LEGGpvggisraekLLDYLNEAGVEVRWTNGTAryrYTHAKYIV 97

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 119576122 172 VD-KRVLITgSLNWTTQAIQNNRENVLITEDDEYVRLFLEEFE 213
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 119576122 123 LHQRGVRVRVVTDcDYmaLNGSQIGLLRK----AGIQVR-HDQDPGYmHHKFAIVDKR---VLITGSLNWTTQAIQNNRE 194
Cdd:cd09204   39 LEERGIKGRILTS-TY--LNFNEPKAFREllklPNIEVRiYDEDEGF-HAKGYIFEHEdyyTIIVGSSNLTQSALKSNYE 114

                         90       100
                 ....*....|....*....|....*
gi 119576122 195 -NVLIT--EDDEYVRLFLEEFERIW 216
Cdd:cd09204  115 wNLKVSstENGDLVEQVLEEFERLW 139

Sugar-specific transcriptional regulator TrmB [Transcription];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119576122 114 PQLGRAVQLLHQRGVRVRVVTDCDYMALngsqIGLLRKAGIQVRHDQDPgymHHKFAIVDKRVLITGSLNwttqaiQNNR 193
Cdd:COG1378  145 EELEEALEEALERGVKVRVLVSPEVLEV----PERLEEEGEEVRVLPGL---PGRLLIVDDKEALISVSE------PDGE 211

                         90       100
                 ....*....|....*....|....*
gi 119576122 194 ENVLITEDDEYVRLFLEEFERIWEQ 218
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 119576122 105 DLCLFAFSSPQLGRAV-QLL---HQRGVRVRVVTDcDY--MALNGSQIGLLRKAGIQVR------HDQDPGYM----HHK 168
Cdd:cd09110   22 HLEYYIFRDDEIGRRFrDALiekARRGVEVRLLYD-GFgsLGLSRRFLRELREAGVEVRafnplsFPLFLLRLnyrnHRK 100

                         90
                 ....*....|....*
gi 119576122 169 FAIVDKRVLITGSLN 183
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 119576122 124 HQRGVRVRVVTDCDYMALNGSQIGL-----------LRKAGIQVRHDQDPGYMHH-KFAIVDKR---VLITGSLNWTTQA 188
Cdd:cd09130   43 ANRGVDVRLILDPNKDAFGREKNGIpnrpvaaelmkKTKGKIQIRWYNTGGEQFHtKLLLIKKKgqaIIIGGSANFTRRN 122

                         90       100       110
                 ....*....|....*....|....*....|...
gi 119576122 189 IQN-NRE-NVLIT--EDDEYVRLFLEEFERIWE 217
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 119576122   162 PGYMHHKFAIVDKRVLITGSLNWT 185
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 119576122 126 RGVRVRVV------TDCDYMALNGS---QIGLLRKAGIQVRHDQDPGY----------MHHKFAIVDKRVLITGSlNWTT 186
Cdd:cd09107   66 RGVKVRLLvsnwkhTDPSMDAFLKSlqlLKSGVGNGDIEVKIFTVPGDqstkipfarvNHAKYMVTDERAYIGTS-NWSG 144

                         90       100       110
                 ....*....|....*....|....*....|.
gi 119576122 187 QAIQNNReNV-LITEDDEYVRLFLEEFERIW 216
Cdd:cd09107  145 DYFYNTA-GVsLVINDPAIVQQLKDVFERDW 174

N-terminal phospholipase D-like domain of proteins from the Family with sequence similarity 83; N-terminal phospholipase D (PLD)-like domain of vetebrate proteins from the Family with sequence similarity 83 (FAM83), which is comprised of 8 members, designated FAM83A through FAM83H. Since the N-terminal PLD-like domain of FAM83 proteins shows only trace similarity to the PLD catalytic domain and lacks the functionally important histidine residue, the FAM83 proteins may share a similar three-dimensional fold with PLD enzymes, but are unlikely to carry PLD activity. Members of the FAM83 are mostly uncharacterized proteins. FAM83A, also known as tumor antigen BJ-TSA-9, is a novel tumor-specific gene highly expressed in human lung adenocarcinoma. FAM83D, also known as spindle protein CHICA, is a cell-cycle-regulated spindle component which localizes to the mitotic spindle and is both upregulated and phosphorylated during mitosis. The gene encoding protein FAM83H is the first gene involved in the etiology of amelogenesis imperfecta (AI), that encodes a non-secreted protein due to the absence of a signal peptide. Defects in gene FAM83H cause autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI). FAM83B, FAM83C, FAM83F, and FAM83G are uncharacterized proteins present across vertebrates while FAM83E is an uncharacterized protein found only in mammals.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119576122 120 VQLLHQRGVRVRVVTDCDYMALNGSQIgllrkagiqvrhdqdPGYMHHKFAIVDKRVLITGSLNWTTQAIQNNRENVLIT 199
Cdd:cd09119  186 LSDEHLKNMRVRSVGGKTYCSRSGKKF---------------KGQMKEKFLLVDGDRVVSGSYSFTWSDAKLHRSMLSVL 250

                         90
                 ....*....|...
gi 119576122 200 EdDEYVRLFLEEF 212
Cdd:cd09119  251 T-GQVVESFDEEF 262

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 119576122 105 DLCLFAFSSPQLGRAV-QLLHQR---GVRVRVVTDcDYMALNGSQIGL--LRKAGIQVR------HDQDPGYM----HHK 168
Cdd:cd09156   22 DVCTFILGDDATGRRViDALARKareGVEVRLLLD-ALGSFFLSRRALkkLRAAGGKVAffmpvfRLPFRGRTnlrnHRK 100

                         90
                 ....*....|....*
gi 119576122 169 FAIVDKRVLITGSLN 183
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 119576122 112 SSPQLGRA-----VQLLH---QRGVRVRVVTD--CDYMALngsqIGLLRKAGIQVRHDQDpgyMHHKFAIVDKRVLITGS 181
Cdd:cd09126   27 SSPYVSQKritklINLLKeaqERGVEVTVVTRepKEYKEL----IEELRSAGVKVKLKEE---IHEKFAIIDKKIVWYGS 99

                 ..
gi 119576122 182 LN 183
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 119576122 125 QRGVRVRVVTDcDYM------ALngSQIGLLRKAGIQVR-HDQDPGYMHHK---FAIVDKR-VLITGSLNWTTQAIQNNR 193
Cdd:cd09205   41 SRGARIRILTG-DYLditqpeAL--RRLLDLLGDGIEIRvFESGGRSFHPKaylFEREDGGgAAFVGSSNLSKSALTDGI 117

                         90       100
                 ....*....|....*....|....*.
gi 119576122 194 E-NVLI--TEDDEYVRLFLEEFERIW 216
Cdd:cd09205  118 EwNLRIdrSADPDAFDEAKEAFEKLF 143