nuclease NucT; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704   4 KFKKIVGVGVLVGCLGVLQAKNSLFVLPYEQKDALNSLVSGISNARESVKIAIYSFTHRDIARAIKSVASRGIKVQIIYD 83
Cdd:PRK13912    1 KMKKIVGVFLLVGCLGVLQAKSSLYFLPYEQKDALNKLVSLISNARSSIKIAIYSFTHKDIAKALKSAAKRGVKISIIYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704  84 YESNHHNKQSTIGYLDKYPNTKVCLLKGLKAKNGNYYGIMHQKVAIIDDKIVFLGSANWSKNAFENNYEVLLKTDDTETI 163
Cdd:PRK13912   81 YESNHNNDQSTIGYLDKYPNIKVCLLKGLKAKNGKYYGIMHQKVAIIDDKIVVLGSANWSKNAFENNYEVLLITDDTETI 160

                         170
                  ....*....|....*..
gi 1900425704 164 LKAKSYYQKMLGSCVGF 180
Cdd:PRK13912  161 LKAKEYFQKMLGSCVGF 177

nuclease NucT; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704   4 KFKKIVGVGVLVGCLGVLQAKNSLFVLPYEQKDALNSLVSGISNARESVKIAIYSFTHRDIARAIKSVASRGIKVQIIYD 83
Cdd:PRK13912    1 KMKKIVGVFLLVGCLGVLQAKSSLYFLPYEQKDALNKLVSLISNARSSIKIAIYSFTHKDIAKALKSAAKRGVKISIIYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704  84 YESNHHNKQSTIGYLDKYPNTKVCLLKGLKAKNGNYYGIMHQKVAIIDDKIVFLGSANWSKNAFENNYEVLLKTDDTETI 163
Cdd:PRK13912   81 YESNHNNDQSTIGYLDKYPNIKVCLLKGLKAKNGKYYGIMHQKVAIIDDKIVVLGSANWSKNAFENNYEVLLITDDTETI 160

                         170
                  ....*....|....*..
gi 1900425704 164 LKAKSYYQKMLGSCVGF 180
Cdd:PRK13912  161 LKAKEYFQKMLGSCVGF 177

PLD-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704  41 LVSGISNARESVKIAIYSF-THRDIARAIKSVASRGIKVQIIYDYESNHH--NKQSTIGYLDKYPNTKVCLLKGLKakng 117
Cdd:pfam13091   1 LIDLINSAKKSIDIATYYFvPDREIIDALIAAAKRGVDVRIILDSNKDDAggPKKASLKELRSLLRAGVEIREYQS---- 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1900425704 118 nYYGIMHQKVAIIDDKIVFLGSANWSKNAFENNYEVLLKTDDTETILKAKSYYQKM 173
Cdd:pfam13091  77 -FLRSMHAKFYIIDGKTVIVGSANLTRRALRLNLENNVVIKDPELAQELEKEFDRL 131

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 1900425704  119 YYGIMHQKVAIIDDKIVFLGSANWSKNA 146
Cdd:smart00155   1 YDGVLHTKLMIVDDEIAYIGSANLDGRS 28

nuclease NucT; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704   4 KFKKIVGVGVLVGCLGVLQAKNSLFVLPYEQKDALNSLVSGISNARESVKIAIYSFTHRDIARAIKSVASRGIKVQIIYD 83
Cdd:PRK13912    1 KMKKIVGVFLLVGCLGVLQAKSSLYFLPYEQKDALNKLVSLISNARSSIKIAIYSFTHKDIAKALKSAAKRGVKISIIYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704  84 YESNHHNKQSTIGYLDKYPNTKVCLLKGLKAKNGNYYGIMHQKVAIIDDKIVFLGSANWSKNAFENNYEVLLKTDDTETI 163
Cdd:PRK13912   81 YESNHNNDQSTIGYLDKYPNIKVCLLKGLKAKNGKYYGIMHQKVAIIDDKIVVLGSANWSKNAFENNYEVLLITDDTETI 160

                         170
                  ....*....|....*..
gi 1900425704 164 LKAKSYYQKMLGSCVGF 180
Cdd:PRK13912  161 LKAKEYFQKMLGSCVGF 177

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 1900425704  34 QKDALNSLVSGISNARESVKIAIYSFTHRDIARAIKSVASRGIKVQIIYDYESNHhNKQSTIGYLDKypntkvcllKGLK 113
Cdd:cd09171     6 GETSLSKLLRYLLSARKSLDVCVFTITCDDLADAILDLHRRGVRVRIITDDDQME-DKGSDIGKLRK---------AGIP 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1900425704 114 AKNGNYYGIMHQKVAIIDDKIVFLGSANWSKNAFENNYEVLLKTDDTETI 163
Cdd:cd09171    76 VRTDLSSGHMHHKFAVIDGKILITGSFNWTRQAVTGNQENVLITNDPKLV 125

PLD-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704  41 LVSGISNARESVKIAIYSF-THRDIARAIKSVASRGIKVQIIYDYESNHH--NKQSTIGYLDKYPNTKVCLLKGLKakng 117
Cdd:pfam13091   1 LIDLINSAKKSIDIATYYFvPDREIIDALIAAAKRGVDVRIILDSNKDDAggPKKASLKELRSLLRAGVEIREYQS---- 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1900425704 118 nYYGIMHQKVAIIDDKIVFLGSANWSKNAFENNYEVLLKTDDTETILKAKSYYQKM 173
Cdd:pfam13091  77 -FLRSMHAKFYIIDGKTVIVGSANLTRRALRLNLENNVVIKDPELAQELEKEFDRL 131

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 1900425704  35 KDALNSLVSGISNARESVKIAIYSFTH----RDIARAIKSVASRGIKVQIIYDYESNHHNKQSTIGYLDKyPNTKVCLLK 110
Cdd:COG1502    24 DEAFAALLEAIEAARRSIDLEYYIFDDdevgRRLADALIAAARRGVKVRVLLDGIGSRALNRDFLRRLRA-AGVEVRLFN 102

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1900425704 111 GLKAKNGNYYGIMHQKVAIIDDKIVFLGSANWSKNAF 147
Cdd:COG1502   103 PVRLLFRRLNGRNHRKIVVIDGRVAFVGGANITDEYL 139

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 1900425704  41 LVSGISNARESVKIAIYSFT-HRDIARAIKSVASRGIKVQIIYDyeSNHHNKQSTIGYLDKYPNT--KVCLLKGLKAKng 117
Cdd:cd09128    15 LLALIDSAEESLLIQNEEMGdDAPILDALVDAAKRGVDVRVLLP--SAWSAEDERQARLRALEGAgvPVRLLKDKFLK-- 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1900425704 118 nyygiMHQKVAIIDDKIVFLGSANWSKNAFENNYEVLLKTDDTEtilkAKSYYQ 171
Cdd:cd09128    91 -----IHAKGIVVDGKTALVGSENWSANSLDRNREVGLIFDDPE----VAAYLQ 135

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 1900425704  41 LVSGISNARESVKIAIYSFTH---RDIARAIKSVASRGIKVQIIYDYESNHHNKQSTIGYLDK-YPNTKVCLLKGLKAKN 116
Cdd:cd00138     3 LLELLKNAKESIFIATPNFSFnsaDRLLKALLAAAERGVDVRLIIDKPPNAAGSLSAALLEALlRAGVNVRSYVTPPHFF 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1900425704 117 GNYygimHQKVAIIDDKIVFLGSANWSKNAFENNYEVLLKT 157
Cdd:cd00138    83 ERL----HAKVVVIDGEVAYVGSANLSTASAAQNREAGVLV 119

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 1900425704  26 SLFVLPyeqKDALNSLVSGISNARESVKIAIYSFTHRDIARAIKSVASRGIKVQIIYDyESNHHNK---QSTIGYLDKYp 102
Cdd:cd09127     1 TLFVQP---DDGVAPVVDAIASAKRSILLKMYEFTDPALEKALAAAAKRGVRVRVLLE-GGPVGGIsraEKLLDYLNEA- 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1900425704 103 NTKVCLLKGLKAkngnyYGIMHQKVAIIDDKIVFLGSANWSKNAFENNYEVLLKTDDTETI 163
Cdd:cd09127    76 GVEVRWTNGTAR-----YRYTHAKYIVVDDERALVLTENFKPSGFTGTRGFGVVTDDPAVV 131

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 1900425704  33 EQKDALNSLVSGISNARESVKIAI-YSFTHRDIARAIKSVASRGIKVQIIYDYESNH----HNKQSTIGYLDKYpNTKVC 107
Cdd:cd09112     8 DWSSIEQAYLKAINSAKKSIYIQTpYFIPDESLLEALKTAALSGVDVRIMIPGKPDHklvyWASRSYFEELLKA-GVKIY 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1900425704 108 LLKGlkakngnyyGIMHQKVAIIDDKIVFLGSANWSKNAFENNYEV 153
Cdd:cd09112    87 EYNK---------GFLHSKTLIVDDEIASVGTANLDIRSFELNFEV 123

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 1900425704  45 ISNARESVKIAIYSFTHR--------------DIARAIKSVASRGIKVQIIYDyESNHHNKQSTIGYLDKYPNTKVcllK 110
Cdd:cd09106    28 ISSAKKSIDIASFYWNLRgtdtnpdssaqegeDIFNALLEAAKRGVKIRILQD-KPSKDKPDEDDLELAALGGAEV---R 103

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1900425704 111 GLKAKNGNYYGIMHQKVAIIDDKIVFLGSANWS 143
Cdd:cd09106   104 SLDFTKLIGGGVLHTKFWIVDGKHFYLGSANLD 136

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 1900425704  39 NSLVSGISNAR--ESVKIAIYSFTHRDIARAIKSVASRGIKVQIIYDyesnhHNK----QSTIGyldkYPNTKVclLKGL 112
Cdd:cd09130     8 EALLKEINSARagDKIWIGMFYLADRDVIKALIDAANRGVDVRLILD-----PNKdafgREKNG----IPNRPV--AAEL 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1900425704 113 KAKNGNYYGI---------MHQKVAII---DDKIVFLGSANWSKNAFEN-NYE--VLLKTD-DTETILKAKSYYQKM 173
Cdd:cd09130    77 MKKTKGKIQIrwyntggeqFHTKLLLIkkkGQAIIIGGSANFTRRNLRDyNLEtdLKILAPnDSPVSKDVDAYFDRL 153

Catalytic domain, repeat 2, of Escherichia coli cardiolipin synthase and similar proteins; Catalytic domain, repeat 2, of Escherichia coli cardiolipin (CL) synthase and similar proteins. Escherichia coli CL synthase (EcCLS), specified by the cls gene, is the prototype of this family. EcCLS is a multi-pass membrane protein that catalyzes reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form cardiolipin (CL) and glycerol. The monomer of EcCLS consists of two catalytic domains. Each catalytic domain contains one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. Two HKD motifs from two domains form a single active site involved in phosphatidyl group transfer. EcCLS can be stimulated by phosphate and inhibited by CL, the product of the reaction, and by phosphatidate. Phosphate stimulation may be unique to enzymes with CL synthase activity belonging to the PLD superfamily. Like other PLD enzymes, EcCLS utilizes a common two-step ping-pong catalytic mechanism involving an enzyme-substrate intermediate to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine residue from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704  41 LVSGISNARESVKIAI-YSFTHRDIARAIKSVASRGIKVQIIYdyesNHHNKQstigyldkypntkvcLLKGLKAKNgnY 119
Cdd:cd09158    16 LLSAIHAARRRVVITTpYFVPDESLLQALCTAALRGVEVTLIL----PAKNDS---------------FLVGAASRS--Y 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1900425704 120 Y---------------GIMHQKVAIIDDKIVFLGSANWSKNAFENNYEVLLKTDDTE 161
Cdd:cd09158    75 YeelleagvkiylyrgGLLHAKTVTVDDEVALVGSSNFDIRSFALNFEISLILYDKE 131

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 1900425704  45 ISNARESVKIAIYSFTHRDIARAIKSV----ASRGIKVQIIYDYESNHHNKQSTIGYLDKY--------PNTkvcllkgL 112
Cdd:cd09110    14 IRAARHSIHLEYYIFRDDEIGRRFRDAliekARRGVEVRLLYDGFGSLGLSRRFLRELREAgvevrafnPLS-------F 86

                          90       100
                  ....*....|....*....|....*....
gi 1900425704 113 KAKNGNYYGIMHQKVAIIDDKIVFLGSAN 141
Cdd:cd09110    87 PLFLLRLNYRNHRKILVIDGKIAFVGGFN 115

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 1900425704  119 YYGIMHQKVAIIDDKIVFLGSANWSKNA 146
Cdd:smart00155   1 YDGVLHTKLMIVDDEIAYIGSANLDGRS 28

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 1900425704  30 LPYEQKDALNSLVSGISNARESVKIA--------IYSFTHR---DIARAIKSVA-SRGIKVQIIYdyeSN-HHNKQSTIG 96
Cdd:cd09107    10 CPPGRTDDLDALLSTIDSAKKFIDISvmdyvplsRYADPRKywpVIDNALRRAAvDRGVKVRLLV---SNwKHTDPSMDA 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704  97 YLdkypntKVCLLKGLKAKNGN-----------------YYGIMHQKVAIIDdKIVFLGSANWSKNAFEN--NYEVLLKT 157
Cdd:cd09107    87 FL------KSLQLLKSGVGNGDievkiftvpgdqstkipFARVNHAKYMVTD-ERAYIGTSNWSGDYFYNtaGVSLVIND 159

                  ....*....
gi 1900425704 158 DDTETILKA 166
Cdd:cd09107   160 PAIVQQLKD 168

N-terminal phospholipase D-like domain of the protein, Family with sequence similarity 83D; N-terminal phospholipase D (PLD)-like domain of the protein Family with sequence similarity 83D (FAM83D), also known as spindle protein CHICA. CHICA is a cell-cycle-regulated spindle component, which localizes to the mitotic spindle and is both upregulated and phosphorylated during mitosis. CHICA is required to localize the chromokinesin Kid to the mitotic spindle and serves as a novel interaction partner of Kid, which is required for the generation of polar ejection forces and chromosome congression. Since the N-terminal PLD-like domain of FAM83D shows only trace similarity to the PLD catalytic domain and lacks the functionally important histidine residue, FAM83D may share a similar three-dimensional fold with PLD enzymes, but is unlikely to carry PLD activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704  31 PYEQKDALNSLvsgISNARESVKIAIYSFTHRDIARAIKSVAS-RGIKVQIIYDYESNHHnkqstigYLDKYPNTKVCL- 108
Cdd:cd09184   122 IYGCKEAARRQ---IRSAREVIALVMDSFTDLDIFRDLREACRkRRVPVYILLDQSSVSH-------FLQMCKNLGVHLe 191

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704 109 -LKGLKAKN--GNYY---------GIMHQKVAIIDDKIVFLGSA--NW------SKNAFENNYEVLLKTDDTETILKAKS 168
Cdd:cd09184   192 qEKLMRVRTitGNTYytrsgakiiGKVHEKFMLIDGIKVATGSYsfTWtdgklnSSNLLILSGQVVEKFDLEFRILYAQS 271

N-terminal phospholipase D-like domain of the uncharacterized protein, Family with sequence similarity 83B; N-terminal phospholipase D (PLD)-like domain of the uncharacterized protein, Family with sequence similarity 83B (FAM83B). 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, FAM83 proteins may share a similar three-dimensional fold with PLD enzymes, but are most unlikely to carry PLD activity. The N-terminus of FAM83B shows high homology to other FAM83 family members, indicating that FAM83B might have arisen early in vertebrate evolution by duplication of a gene in the FAM83 family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704  45 ISNARESVKIAIYSFTHRDIARAIKSVASRGIKVQIIYDYESNHH-----NKQSTigYLDKYPNTKVCLLKG--LKAKNG 117
Cdd:cd09182   126 IQEARQVIAIAMDVFTDVDIFKEVVEASTRGVAVYILLDHSHFASfltmtEKQGI--QIQRLRNIRVRTVKGqdYQCKSG 203

                          90       100
                  ....*....|....*....|....*....
gi 1900425704 118 -NYYGIMHQKVAIIDDKIVFLGSAN--WS 143
Cdd:cd09182   204 aKFHGAMEQKFLLVDCQKVLYGSYSymWS 232

Catalytic domain, repeat 2, of vertebrate phospholipases, PLD1 and PLD2, and similar proteins; Catalytic domain, repeat 2, of phospholipase D (PLD, EC 3.1.4.4) found in yeast, plants, and vertebrates, and their bacterial homologs. PLDs are involved in signal transduction, vesicle formation, protein transport, and mitosis by participating in phospholipid metabolism. They hydrolyze the terminal phosphodiester bond of phospholipids resulting in the formation of phosphatidic acid and alcohols. Phosphatidic acid is an essential compound involved in signal transduction. PLDs also catalyze the transphosphatidylation of phospholipids to acceptor alcohols, by which various phospholipids can be synthesized. Both prokaryotic and eukaryotic PLDs have two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. PLDs are active as bi-lobed monomers. Each monomer contains two domains, each of which carries one copy of the HKD motif. Two HKD motifs from two domains form a single active site. PLDs utilize a common two-step ping-pong catalytic mechanism involving an enzyme-substrate intermediate to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine residue from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704  41 LVSGISNARESVKIAIYSFTHRDI----ARAIKsvASRGIKVQII---------------YDYESNHHNKQSTIGYLDKY 101
Cdd:cd09105    13 YLKAIRNARRYIYIEDQYLWSPELldalAEALK--ANPGLRVVLVlpalpdavafgaddgLDALALLALLLLADAAPDRV 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1900425704 102 pntKVCLLKGLKAKNGNYYGI-MHQKVAIIDDKIVFLGSANWSKNAFENNYEV 153
Cdd:cd09105    91 ---AVFSLATHRRGLLGGPPIyVHSKVVIVDDEWATVGSANLNRRSMTWDTEL 140

Putative catalytic domain, repeat 1, of Escherichia coli uncharacterized protein ymdC and similar proteins; Putative catalytic domain, repeat 1, of Escherichia coli uncharacterized protein ymdC and similar proteins. In Escherichia coli, there are two genes, f413 (ybhO) and o493 (ymdC), which are homologous to gene cls that encodes the Escherichia coli cardiolipin (CL) synthase. The prototype of this subfamily is an uncharacterized protein ymdC specified by the o493 (ymdC) gene. Although the functional characterization of ymdC and similar proteins remains unknown, members of this subfamily show high sequence homology to bacterial CL synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Moreover, ymdC and its similar proteins contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characteriszes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1900425704  36 DALNSLVSGISNARESVKIAIYSFtHRD-----IARAIKSVASRGIKVQIIYDyESNHHNKQSTIGYLDKYPNTKVCLLK 110
Cdd:cd09111     6 DALAARLALIRSAERSIDLQYYIW-HDDesgrlLLGELLEAADRGVRVRLLLD-DLGTSGRDRLLAALDAHPNIEVRLFN 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1900425704 111 GLKAKNGNYYGI----------MHQKVAIIDDKIVFLGSANWSKNAFENNYEV 153
Cdd:cd09111    84 PFRNRGGRLLEFltdfsrlnrrMHNKLFIVDGAVAIVGGRNIGDEYFGASPEV 136

Catalytic domain, repeat 2, of vertebrate phospholipases, PLD1 and PLD2, yeast PLDs, and similar proteins; Catalytic domain, repeat 2, of vertebrate phospholipases D (PLD1 and PLD2), yeast phospholipase D (PLD SPO14/PLD1), and other similar eukaryotic proteins. These PLD enzymes play a pivotal role in transmembrane signaling and cellular regulation. They hydrolyze the terminal phosphodiester bond of phospholipids resulting in the formation of phosphatidic acid and alcohols. Phosphatidic acid is an essential compound involved in signal transduction. PLDs also catalyze the transphosphatidylation of phospholipids to acceptor alcohols, by which various phospholipids can be synthesized. The vertebrate PLD1 and PLD2 are membrane associated phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent enzymes that selectively hydrolyze phosphatidylcholine (PC). Protein cofactors and calcium may be required for their activation. Yeast SPO14/PLD1 is a calcium-independent PLD, which needs PIP2 for its activity. Instead of the regulatory calcium-dependent phospholipid-binding C2 domain in plants, most mammalian and yeast PLDs have adjacent Phox (PX) and the Pleckstrin homology (PH) domains at the N-terminus, which have been shown to mediate membrane targeting of the protein and are closely linked to polyphosphoinositide signaling. The PX and PH domains are also present in zeta-type PLD from Arabidopsis, which is more closely related to vertebrate PLDs than to other plant PLD types. In addition, this subfamily also includes some related proteins which have either PX-like or PH domains in their N-termini. Like other members of the PLD superfamily, the monomer of mammalian and yeast PLDs consists of two catalytic domains, each containing one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue). Two HKD motifs from the two domains form a single active site. These PLDs utilize a common two-step ping-pong catalytic mechanism involving an enzyme-substrate intermediate to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine residue from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1900425704  75 GIKVQIIYDYESNHHNKQSTIGYLDKYPNT------KVCLLKGLKAKNGNYYGIM---HQKVAIIDDKIVFLGSAN 141
Cdd:cd09141    86 SIRAIMHWQYQSICRGEHSLLERLKKEEGVdpeqyiSFLSLRTHGKLGGRPVTEQiyvHSKLMIVDDRIVIIGSAN 161

Putative catalytic domain, repeat 2, of Escherichia coli uncharacterized protein ymdC and similar proteins; Putative catalytic domain, repeat 2, of Escherichia coli uncharacterized protein ymdC and similar proteins. In Escherichia coli, there are two genes, f413 (ybhO) and o493 (ymdC), which are homologous to gene cls that encodes the Escherichia coli cardiolipin (CL) synthase. The prototype of this subfamily is an uncharacterized protein ymdC specified by the o493 (ymdC) gene. Although the functional characterization of ymdC and similar proteins remains unknown, members of this subfamily show high sequence homology to bacterial CL synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Moreover, ymdC and its similar proteins contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characteriszes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                          10        20
                  ....*....|....*....|
gi 1900425704 123 MHQKVAIIDDKIVFLGSANW 142
Cdd:cd09113   117 LHAKSFVIDDRLVFVGSFNL 136