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 1958762124   1 MDVFSDIDIFRDLQEICRKRGVAVYILLDQALLSHFLDMCMDLKVHPEQEKLMTVRTITGNIYYARSGTKVVGKVHEKFT 80
Cdd:cd09184   144 MDSFTDLDIFRDLREACRKRRVPVYILLDQSSVSHFLQMCKNLGVHLEQEKLMRVRTITGNTYYTRSGAKIIGKVHEKFM 223

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958762124  81 LIDGIRVATGSYSFTWTDGKLNSSNLVILSGQVVEHFDLEFRILYAQS 128
Cdd:cd09184   224 LIDGIKVATGSYSFTWTDGKLNSSNLLILSGQVVEKFDLEFRILYAQS 271

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 1958762124   1 MDVFSDIDIFRDLQEICRKRGVAVYILLDQALLSHFLDMCMDLKVHPEQEKLMTVRTITGNIYYARSGTKVVGKVHEKFT 80
Cdd:cd09184   144 MDSFTDLDIFRDLREACRKRRVPVYILLDQSSVSHFLQMCKNLGVHLEQEKLMRVRTITGNTYYTRSGAKIIGKVHEKFM 223

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958762124  81 LIDGIRVATGSYSFTWTDGKLNSSNLVILSGQVVEHFDLEFRILYAQS 128
Cdd:cd09184   224 LIDGIKVATGSYSFTWTDGKLNSSNLLILSGQVVEKFDLEFRILYAQS 271

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 1958762124   1 MDVFSDIDIFRDLQEICRKRGVAVYILLDQALLSHFLDMCMDLKVHPEQEKLMTVRTITGNIYYARSGTKVVGKVHEKFT 80
Cdd:cd09184   144 MDSFTDLDIFRDLREACRKRRVPVYILLDQSSVSHFLQMCKNLGVHLEQEKLMRVRTITGNTYYTRSGAKIIGKVHEKFM 223

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958762124  81 LIDGIRVATGSYSFTWTDGKLNSSNLVILSGQVVEHFDLEFRILYAQS 128
Cdd:cd09184   224 LIDGIKVATGSYSFTWTDGKLNSSNLLILSGQVVEKFDLEFRILYAQS 271

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 1958762124   1 MDVFSDIDIFRDLQEICRKRGVAVYILLDQALLSHFLDMCMDLKVHPEQEKLMTVRTITGNIYYARSGTKVVGKVHEKFT 80
Cdd:cd09119   142 MDVFTDVDIFCDLLEAANKRGVAVYILLDQGNVKHFLEMCDKLQLSDEHLKNMRVRSVGGKTYCSRSGKKFKGQMKEKFL 221

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958762124  81 LIDGIRVATGSYSFTWTDGKLNSSNLVILSGQVVEHFDLEFRILYAQS 128
Cdd:cd09119   222 LVDGDRVVSGSYSFTWSDAKLHRSMLSVLTGQVVESFDEEFRILYAQS 269

N-terminal phospholipase D-like domain of the uncharacterized protein, Family with sequence similarity 83C; N-terminal phospholipase D (PLD)-like domain of the uncharacterized protein, Family with sequence similarity 83C (FAM83C). 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 FAM83C shows high homology to other FAM83 family members, indicating that FAM83C 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 1958762124   1 MDVFSDIDIFRDLQEICRKRGVAVYILLDQALLSHFLDMCMDLKVHPEQEKLMTVRTITGNIYYARSGTKVVGKVHEKFT 80
Cdd:cd09183   147 MDLFTDVDILCDLMEASNKRRVPVYLLLDEENLGHFLEMCEKLDLNKTSLPNMRIRSVCGDTYCTKSGKKFTGQVLEKFL 226

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958762124  81 LIDGIRVATGSYSFTWTDGKLNSSNLVILSGQVVEHFDLEFRILYAQS 128
Cdd:cd09183   227 LIDCEQVVAGSYSFTWLSSQVHSNLVTHFRGNIVEEFDREFRCLYADS 274

N-terminal phospholipase D-like domain of the uncharacterized protein Family with sequence similarity 83G; N-terminal phospholipase D (PLD)-like domain of the uncharacterized protein, Family with sequence similarity 83G (FAM83G). 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 FAM83G shows high homology to other FAM83 family members, indicating that FAM83G 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 1958762124   1 MDVFSDIDIFRDLQEICRKRGVAVYILLDQALLSHFLDMCMDLKVHPEQEKLMTVRTITGNIYYARSGTKVVGKVHEKFT 80
Cdd:cd09187   148 MDMFTDVDIFRDLLDAGFKRKVPVYIILDETNVKYFLQMCERAQMHRGHLKNLRVRSCGGTEFFTRSATKFKGSLGQKFM 227

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958762124  81 LIDGIRVATGSYSFTWTDGKLNSSNLVILSGQVVEHFDLEFRILYAQS 128
Cdd:cd09187   228 FVDGDRAICGSYSFTWSASRTDRNLITVLSGQVVETFDRQFQDLYLMS 275

N-terminal phospholipase D-like domain of the uncharacterized protein, Family with sequence similarity 83H; N-terminal phospholipase D (PLD)-like domain of the protein, Family with sequence similarity 83H (FAM83H) on chromosome 8q24.3, which localizes in the intracellular environment and is associated with vesicles, can be regulated by kinases, and plays important roles during ameloblast differentiation and enamel matrix calcification. 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). Since the N-terminal PLD-like domain of FAM83H shows only trace similarity to the PLD catalytic domain and lacks the functionally important histidine residue, FAM83H may share a similar three-dimensional fold with PLD enzymes, but is most unlikely to carry PLD activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762124   1 MDVFSDIDIFRDLQEICRKRgVAVYILLDQALLSHFLDMCMDLKVHPEQEKLMTVRTITGNIYYARSGTKVVGKVHEKFT 80
Cdd:cd09188   139 MDIFTDVDILSELLEAAARR-VPVYILLDEMNAQLFLDMAAKCRVNLNYVEFLRVRTVSGPTYFCRTGKSFKGHVKEKFL 217

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958762124  81 LIDGIRVATGSYSFTWTDGKLNSSNLVILSGQVVEHFDLEFRILYAQS 128
Cdd:cd09188   218 LVDCRVVLSGNYSFMWSFEKIHRSIAHIFQGELVASFDEEFRILFAQS 265

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 1958762124   3 VFSDIDIFRDLQEiCRKRGVAVYILLDQALLShfldmcmdlkvhpEQEKLMTvrtitgniYYARSGTKV-----VGKVHE 77
Cdd:cd09170    33 SFTSPPIARALIA-AKKRGVDVRVVLDKSQAG-------------GKYSALN--------YLANAGIPVriddnYAIMHN 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958762124  78 KFTLIDGIRVATGSYSFTWTDGKLNSSNLVILSG--QVVEHFDLEFRILYAQ 127
Cdd:cd09170    91 KVMVIDGKTVITGSFNFTASAEKRNAENLLVIRNppELAQQYLQEWQRRWAQ 142

PLD-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762124   5 SDIDIFRDLQEiCRKRGVAVYILLDQALLSHFLdmcmdlKVHPEQEKLMTVRTITGNIYYarsGTKVVGKVHEKFTLIDG 84
Cdd:pfam13091  21 PDREIIDALIA-AAKRGVDVRIILDSNKDDAGG------PKKASLKELRSLLRAGVEIRE---YQSFLRSMHAKFYIIDG 90

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958762124  85 IRVATGSYSFTWTDGKLNS-SNLVILSGQVVEHFDLEF 121
Cdd:pfam13091  91 KTVIVGSANLTRRALRLNLeNNVVIKDPELAQELEKEF 128

Putative catalytic domain of uncharacterized hypothetical proteins closely related to Nuc, , an endonuclease from Salmonella typhimurium; Putative catalytic domain 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 1958762124   4 FSDIDIFRDLqEICRKRGVAVYILLDQallSHFLDMCMDLKVHPEQEklmtvrtiTGNIYYarSGTKVVGKVHEKFTLID 83
Cdd:cd09174    30 FTNKDIFNAL-KNKKKEGVNIQIIIND---DDINKKDVLILDEDSFE--------IYKLPG--NGSRYGNLMHNKFCVID 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1958762124  84 GIRVATGSYSftWTD-GKLNSSNLVIL-SGQVVEHFDLEFRIL 124
Cdd:cd09174    96 FKTVITGSYN--WTKnAEYNFENIIITdDRELAEQFAKEFIKL 136