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 590114095  92 ELCLFAFSSPQLGRAVQLLHQRGVRVRVITDCDYMALNGSQIGLLRKAGIQVRHDQDLGYMHHKFAIVDKKVLITGSLNW 171
Cdd:cd09171   25 DVCVFTITCDDLADAILDLHRRGVRVRIITDDDQMEDKGSDIGKLRKAGIPVRTDLSSGHMHHKFAVIDGKILITGSFNW 104

                         90       100       110
                 ....*....|....*....|....*....|..
gi 590114095 172 TTQAIQNNRENVLIMEDTEYVRLFLEEFERIW 203
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 590114095  92 ELCLFAFSSPQLGRAVQLLHQRGVRVRVITDCDYMALNGSQIGLLRKAGIQVRHDQDLGYMHHKFAIVDKKVLITGSLNW 171
Cdd:cd09171   25 DVCVFTITCDDLADAILDLHRRGVRVRIITDDDQMEDKGSDIGKLRKAGIPVRTDLSSGHMHHKFAVIDGKILITGSFNW 104

                         90       100       110
                 ....*....|....*....|....*....|..
gi 590114095 172 TTQAIQNNRENVLIMEDTEYVRLFLEEFERIW 203
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 590114095 100 SPQLGRAVQLLHQRGVRVRVITDC--DYMALNG---SQIGLLRKAGIQVRHDQDlGYMHHKFAIVDKKVLITGSLNWTTQ 174
Cdd:COG1502  229 DRSLLRALIAAARRGVDVRILLPAksDHPLVHWasrSYYEELLEAGVRIYEYEP-GFLHAKVMVVDDEWALVGSANLDPR 307

                         90       100       110
                 ....*....|....*....|....*....|.
gi 590114095 175 AIQNNRENVLIMEDTEYVRLFLEEFERIWEE 205
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 590114095   149 LGYMHHKFAIVDKKVLITGSLNWT 172
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 590114095  92 ELCLFAFSSPQLGRAVQLLHQRGVRVRVITDCDYMALNGSQIGLLRKAGIQVRHDQDLGYMHHKFAIVDKKVLITGSLNW 171
Cdd:cd09171   25 DVCVFTITCDDLADAILDLHRRGVRVRIITDDDQMEDKGSDIGKLRKAGIPVRTDLSSGHMHHKFAVIDGKILITGSFNW 104

                         90       100       110
                 ....*....|....*....|....*....|..
gi 590114095 172 TTQAIQNNRENVLIMEDTEYVRLFLEEFERIW 203
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 590114095  96 FAFSSPQLGRAVQLLHQRGVRVRVITDCDYMALNGSQIGLLRKAGIQVRHDQDLGYMHHKFAIVDKKVLITGSLNWTTQA 175
Cdd:cd09170   32 YSFTSPPIARALIAAKKRGVDVRVVLDKSQAGGKYSALNYLANAGIPVRIDDNYAIMHNKVMVIDGKTVITGSFNFTASA 111

                         90       100       110
                 ....*....|....*....|....*....|.
gi 590114095 176 IQNNRENVLIMED-TEYVRLFLEEFERIWEE 205
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 590114095 100 SPQLGRAVQLLHQRGVRVRVITDC--DYMALNG---SQIGLLRKAGIQVRHDQDlGYMHHKFAIVDKKVLITGSLNWTTQ 174
Cdd:COG1502  229 DRSLLRALIAAARRGVDVRILLPAksDHPLVHWasrSYYEELLEAGVRIYEYEP-GFLHAKVMVVDDEWALVGSANLDPR 307

                         90       100       110
                 ....*....|....*....|....*....|.
gi 590114095 175 AIQNNRENVLIMEDTEYVRLFLEEFERIWEE 205
Cdd:COG1502  308 SLRLNFEVNLVIYDPEFAAQLRARFEEDLAH 338

nuclease NucT; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 590114095  95 LFAFSSPQLGRAVQLLHQRGVRVRVITDCDYMALNG-SQIGLLRKA---------GIQVRHDQDLGYMHHKFAIVDKKVL 164
Cdd:PRK13912  53 IYSFTHKDIAKALKSAAKRGVKISIIYDYESNHNNDqSTIGYLDKYpnikvcllkGLKAKNGKYYGIMHQKVAIIDDKIV 132

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 590114095 165 ITGSLNWTTQAIQNNRENVLIMEDTEYVRLFLEEFERI 202
Cdd:PRK13912 133 VLGSANWSKNAFENNYEVLLITDDTETILKAKEYFQKM 170

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 590114095  93 LCLFAFSSPQLGRAV-QLL---HQRGVRVRVITDcDY--MALNGSQIGLLRKAGIQVR--------HDQDLGYMHHKFAI 158
Cdd:COG1502   43 LEYYIFDDDEVGRRLaDALiaaARRGVKVRVLLD-GIgsRALNRDFLRRLRAAGVEVRlfnpvrllFRRLNGRNHRKIVV 121

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 590114095 159 VDKKVLITGSLNWT------TQAIQNNRENVLIMEDTEyVRLFLEEFERIWE 204
Cdd:COG1502  122 IDGRVAFVGGANITdeylgrDPGFGPWRDTHVRIEGPA-VADLQAVFAEDWN 172

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 590114095  93 LCLFAFSSPQLGRAVQLLHQRGVRVRVITDCDYMALNGSQI---GLLRKAGIQ----------VRHDQD--LGYMHHKFA 157
Cdd:cd09173   27 FALFDFSDGALLDALLAAADAGLFVRGLVDKRFGGRYYSAAadmGGIDPVYPAalapdepekfVGEPLLgvGDKLHHKFM 106

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 590114095 158 IVD----KKVLITGSLNWTTQAIQNNRENVLIMEDTEYVRLFLEEFERIWEEF 206
Cdd:cd09173  107 VIDpfgdDPVVITGSHNFSGAANDNNDENLLVIRDPAIADAYAIEFLRLYDHY 159

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 590114095  94 CLFAFSSPQLGRAVQLLHQRGVRVRVITD---CDYMALNGSQIGLLRKAGIQVR----HDQDLGYMHHKFAIVDKKVLIT 166
Cdd:cd00138   20 NFSFNSADRLLKALLAAAERGVDVRLIIDkppNAAGSLSAALLEALLRAGVNVRsyvtPPHFFERLHAKVVVIDGEVAYV 99

                         90       100
                 ....*....|....*....|
gi 590114095 167 GSLNWTTQAIQNNRENVLIM 186
Cdd:cd00138  100 GSANLSTASAAQNREAGVLV 119

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 590114095 110 LHQRGVRVRVITDcDYmaLNGSQIGLLRK----AGIQVR-HDQDLGYmHHKFAIVDKK---VLITGSLNWTTQAIQNNRE 181
Cdd:cd09204   39 LEERGIKGRILTS-TY--LNFNEPKAFREllklPNIEVRiYDEDEGF-HAKGYIFEHEdyyTIIVGSSNLTQSALKSNYE 114

                         90       100
                 ....*....|....*....|....*
gi 590114095 182 -NVLI--MEDTEYVRLFLEEFERIW 203
Cdd:cd09204  115 wNLKVssTENGDLVEQVLEEFERLW 139

Sugar-specific transcriptional regulator TrmB [Transcription];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 590114095 101 PQLGRAVQLLHQRGVRVRVITDCDYMALngsqIGLLRKAGIQVRHDQDlgyMHHKFAIVDKKVLITGSLNwttqaiQNNR 180
Cdd:COG1378  145 EELEEALEEALERGVKVRVLVSPEVLEV----PERLEEEGEEVRVLPG---LPGRLLIVDDKEALISVSE------PDGE 211

                         90       100
                 ....*....|....*....|....*
gi 590114095 181 ENVLIMEDTEYVRLFLEEFERIWEE 205
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 590114095  93 LCLFAFSSPQLGRAV-QLL---HQRGVRVRVITDcDY--MALNGSQIGLLRKAGIQVR--HDQDLGY--------MHHKF 156
Cdd:cd09110   23 LEYYIFRDDEIGRRFrDALiekARRGVEVRLLYD-GFgsLGLSRRFLRELREAGVEVRafNPLSFPLfllrlnyrNHRKI 101

                         90
                 ....*....|....
gi 590114095 157 AIVDKKVLITGSLN 170
Cdd:cd09110  102 LVIDGKIAFVGGFN 115

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 590114095  99 SSPQLGRAV----QLLHQRGVRVRVITDCDYMALNGSQIGLLRKAGIQVRHDQ----DLGYMHHKFAIVDKKVLITGSLN 170
Cdd:cd09145   55 SSSLPGEDIlkelAELLSRNVSVRAAASIPTLAANSTDLKILRQKGAHVRKVNfgrlTGGVLHSKFWIIDKKHIYVGSAN 134

                         90
                 ....*....|.
gi 590114095 171 WTTQAIQNNRE 181
Cdd:cd09145  135 MDWRSLTQVKE 145

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 590114095   149 LGYMHHKFAIVDKKVLITGSLNWT 172
Cdd:smart00155   2 DGVLHTKLMIVDDEIAYIGSANLD 25

C-terminal domain of Escherichia coli uncharacterized protein yjhR and similar proteins; C-terminal domain of Escherichia coli uncharacterized protein yjhR, encoded by the o338 gene, and similar proteins. Although the biological function of yjhR remains unknown, it shows sequence similarity to the C-terminal portions of superfamily I DNA and RNA helicases, which are ubiquitous enzymes mediating ATP-dependent unwinding of DNA and RNA duplexes, and play essential roles in gene replication and expression. Moreover, The C-termini of yjhR and similar proteins contain one HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. The PLDc-like domain of yjhR is similar to bacterial endonucleases, Nuc and BfiI, both of which have only one copy of the HKD motif per chain. They function as homodimers, with a single active site at the dimer interface containing the HKD motifs from both subunits. They 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 590114095 112 QRGVRVRVITD--CDYMALNGSQIGL------LRKAGIQVrHDQDLgyMHHKFAIVDKKVLITGSLNW 171
Cdd:cd09118   43 SRGVDVTIYTDphLNTGDANDTKANLedaaeaLAEAGIRI-HEVNG--VHSKIVIVDNHLLAVGSFNW 107

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 590114095 133 IGLLRKAGIQVR-HDQdlGYMHHKFAIVDKK-------VLITGSLNWTTQAIQNNRE-NVlIMEDTEYVRLFLEEFERIW 203
Cdd:cd09178   55 IELIKEGKVEIRvYTK--GFLHAKAYLFDGPdndngpgTAIVGSSNFTKAGLTGNLElNV-EVKDRDDVEELKEWFEELW 131

                 ..
gi 590114095 204 EE 205
Cdd:cd09178  132 ED 133

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 590114095  98 FSSPQLGRAV--QLLH--QRGVRVRVITDcdYMALNGSQIG---LLRKAGIQVR--HDQDL---GYMHHKFAIVDKKVLI 165
Cdd:cd09106   52 DSSAQEGEDIfnALLEaaKRGVKIRILQD--KPSKDKPDEDdleLAALGGAEVRslDFTKLiggGVLHTKFWIVDGKHFY 129

                 ....*..
gi 590114095 166 TGSLNWT 172
Cdd:cd09106  130 LGSANLD 136

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 590114095 113 RGVRVRVI------TDCDYMALNGS---QIGLLRKAGIQVR-----HDQDLGY-----MHHKFAIVDKKVLITGSlNWTT 173
Cdd:cd09107   66 RGVKVRLLvsnwkhTDPSMDAFLKSlqlLKSGVGNGDIEVKiftvpGDQSTKIpfarvNHAKYMVTDERAYIGTS-NWSG 144

                         90       100       110
                 ....*....|....*....|....*....|.
gi 590114095 174 QAIQNNReNV-LIMEDTEYVRLFLEEFERIW 203
Cdd:cd09107  145 DYFYNTA-GVsLVINDPAIVQQLKDVFERDW 174