Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: LPCAT1-like; Lysophospholipid acyltransferase (LPLAT) superfamily member: acyltransferases of de novo and remodeling pathways of glycerophospholipid biosynthesis which catalyze the incorporation of an acyl group from either acylCoAs or acyl-acyl carrier proteins (acylACPs) into acceptors such as glycerol 3-phosphate, dihydroxyacetone phosphate or lyso-phosphatidic acid. Included in this subgroup are such LPLATs as lysophosphatidylcholine acyltransferase 1 (LPCAT-1), glycerol-3-phosphate acyltransferase 3 (GPAT3), and similar sequences.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 116 RAMFFSMGF-IVSVKGRIASPLEAPVFVAaPHSTFFDGIACVVAGLPSMVSRNENAQVPLIGRMLRAVQPILVSRVDPDS 194
Cdd:cd07991    2 RVLLFAFGFyVIKVHGKPDPPEAPRIIVA-NHTSFIDPLILFSDLFPSIVAKKELGKLPFIGTILRALGCIFVDRSEPKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 195 RKNTINEIIKRTTSGgEWPQILVFPEGTCTNRSCLITFKPGAFIPGVPVQPVLLRYPNKLDTVTWTWQGYTFIQLCMLTF 274
Cdd:cd07991   81 RKKVVEEIKERATDP-NWPPILIFPEGTTTNGKALIMFKKGAFEPGVPVQPVAIRYPNKFVDAFWNSSGYSSLMYLFRLL 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 109128545 275 CQLFTKVEVEFMPVQVPNdEEKNDPVLFANKVRNVMAEALGIPVTDHTYEDCR 327
Cdd:cd07991  160 TQPANVLEVEFLPVYTPS-EEGEDPKEFANRVRLIMANKLGLPATDWTGEDKR 211

Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: LPCAT1-like; Lysophospholipid acyltransferase (LPLAT) superfamily member: acyltransferases of de novo and remodeling pathways of glycerophospholipid biosynthesis which catalyze the incorporation of an acyl group from either acylCoAs or acyl-acyl carrier proteins (acylACPs) into acceptors such as glycerol 3-phosphate, dihydroxyacetone phosphate or lyso-phosphatidic acid. Included in this subgroup are such LPLATs as lysophosphatidylcholine acyltransferase 1 (LPCAT-1), glycerol-3-phosphate acyltransferase 3 (GPAT3), and similar sequences.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 116 RAMFFSMGF-IVSVKGRIASPLEAPVFVAaPHSTFFDGIACVVAGLPSMVSRNENAQVPLIGRMLRAVQPILVSRVDPDS 194
Cdd:cd07991    2 RVLLFAFGFyVIKVHGKPDPPEAPRIIVA-NHTSFIDPLILFSDLFPSIVAKKELGKLPFIGTILRALGCIFVDRSEPKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 195 RKNTINEIIKRTTSGgEWPQILVFPEGTCTNRSCLITFKPGAFIPGVPVQPVLLRYPNKLDTVTWTWQGYTFIQLCMLTF 274
Cdd:cd07991   81 RKKVVEEIKERATDP-NWPPILIFPEGTTTNGKALIMFKKGAFEPGVPVQPVAIRYPNKFVDAFWNSSGYSSLMYLFRLL 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 109128545 275 CQLFTKVEVEFMPVQVPNdEEKNDPVLFANKVRNVMAEALGIPVTDHTYEDCR 327
Cdd:cd07991  160 TQPANVLEVEFLPVYTPS-EEGEDPKEFANRVRLIMANKLGLPATDWTGEDKR 211

Phosphate acyltransferases; Function in phospholipid biosynthesis and have either glycerolphosphate, 1-acylglycerolphosphate, or 2-acylglycerolphosphoethanolamine acyltransferase activities. Tafazzin, the product of the gene mutated in patients with Barth syndrome, is a member of this family.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545   142 VAAPHSTFFDGIACVVA-----GLPSMVSRNENAQVPLIGRMLRAVQPILVSRVDPDSRKNTINEIIKRTTSGGewpQIL 216
Cdd:smart00563   3 VVANHQSFLDPLVLSALlprklGRVRFVAKKELFYVPLLGWLLRLLGAIFIDRSNGRKARAALREAVELLKEGE---WLL 79

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 109128545   217 VFPEGTCTNRSCLITFKPGAFI----PGVPVQPVLLRY 250
Cdd:smart00563  80 IFPEGTRSRPGKLLPFKKGAARlaleAGVPIVPVAIRG 117

Acyltransferase; This family contains acyltransferases involved in phospholipid biosynthesis and other proteins of unknown function. This family also includes tafazzin, the Barth syndrome gene.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545  126 VSVKGRIASPLEAPVFVAAPHSTFFDGI--ACVVA---GLPSMVSRNENAQVPLIGRMLRAVQPILVSRVDPDSRKNTIN 200
Cdd:pfam01553   2 IEVHGLENLPRGGPAIVVANHQSYLDVLllSLALYkrgRPLVFVAKKELFDIPLVGWLMRLLGCIFIDRKNRKDAAGTLE 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 109128545  201 EIIKRTTSGGewpQILVFPEGTCTNRSCLITFKPGAFI----PGVPVQPV 246
Cdd:pfam01553  82 YLVELLREGK---LVVIFPEGTRSREGELLPFKKGAFRlaieAGVPIVPV 128

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 109128545  394 DVLRQLFALFDRNHDGSIDFREYVIGLAVLCNPAN-TEEIIQVAFKLFDVDEDGYITEEEFSTILQ 458
Cdd:pfam13499   2 EKLKEAFKLLDSDGDGYLDVEELKKLLRKLEEGEPlSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

calmodulin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 404 DRNHDGSIDFREYVIGLAVLCNPANTEEIIQVAFKLFDVDEDGYITEEEFSTILqASLG--VPDLDVSGLFKEI-AQGD- 479
Cdd:PTZ00184  57 DADGNGTIDFPEFLTLMARKMKDTDSEEEIKEAFKVFDRDGNGFISAAELRHVM-TNLGekLTDEEVDEMIREAdVDGDg 135

                 ....*..
gi 109128545 480 SISYEEF 486
Cdd:PTZ00184 136 QINYEEF 142

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.

                           10        20
                   ....*....|....*....|....*..
gi 109128545   433 IQVAFKLFDVDEDGYITEEEFSTILQA 459
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDLLKA 28

Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: LPCAT1-like; Lysophospholipid acyltransferase (LPLAT) superfamily member: acyltransferases of de novo and remodeling pathways of glycerophospholipid biosynthesis which catalyze the incorporation of an acyl group from either acylCoAs or acyl-acyl carrier proteins (acylACPs) into acceptors such as glycerol 3-phosphate, dihydroxyacetone phosphate or lyso-phosphatidic acid. Included in this subgroup are such LPLATs as lysophosphatidylcholine acyltransferase 1 (LPCAT-1), glycerol-3-phosphate acyltransferase 3 (GPAT3), and similar sequences.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 116 RAMFFSMGF-IVSVKGRIASPLEAPVFVAaPHSTFFDGIACVVAGLPSMVSRNENAQVPLIGRMLRAVQPILVSRVDPDS 194
Cdd:cd07991    2 RVLLFAFGFyVIKVHGKPDPPEAPRIIVA-NHTSFIDPLILFSDLFPSIVAKKELGKLPFIGTILRALGCIFVDRSEPKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 195 RKNTINEIIKRTTSGgEWPQILVFPEGTCTNRSCLITFKPGAFIPGVPVQPVLLRYPNKLDTVTWTWQGYTFIQLCMLTF 274
Cdd:cd07991   81 RKKVVEEIKERATDP-NWPPILIFPEGTTTNGKALIMFKKGAFEPGVPVQPVAIRYPNKFVDAFWNSSGYSSLMYLFRLL 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 109128545 275 CQLFTKVEVEFMPVQVPNdEEKNDPVLFANKVRNVMAEALGIPVTDHTYEDCR 327
Cdd:cd07991  160 TQPANVLEVEFLPVYTPS-EEGEDPKEFANRVRLIMANKLGLPATDWTGEDKR 211

Phosphate acyltransferases; Function in phospholipid biosynthesis and have either glycerolphosphate, 1-acylglycerolphosphate, or 2-acylglycerolphosphoethanolamine acyltransferase activities. Tafazzin, the product of the gene mutated in patients with Barth syndrome, is a member of this family.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545   142 VAAPHSTFFDGIACVVA-----GLPSMVSRNENAQVPLIGRMLRAVQPILVSRVDPDSRKNTINEIIKRTTSGGewpQIL 216
Cdd:smart00563   3 VVANHQSFLDPLVLSALlprklGRVRFVAKKELFYVPLLGWLLRLLGAIFIDRSNGRKARAALREAVELLKEGE---WLL 79

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 109128545   217 VFPEGTCTNRSCLITFKPGAFI----PGVPVQPVLLRY 250
Cdd:smart00563  80 IFPEGTRSRPGKLLPFKKGAARlaleAGVPIVPVAIRG 117

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 377 GRIGIDEFAKYLklpvSDVLRQLFALFDRNHDGSIDFREYVIGLAVLCNPANTEEIIQvAFKLFDVDEDGYITEEEFSTI 456
Cdd:COG5126   20 GVLERDDFEALF----RRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARA-AFDLLDTDGDGKISADEFRRL 94

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 109128545 457 LQAsLGVPDLDVSGLFKEI-AQGD-SISYEEFKSF 489
Cdd:COG5126   95 LTA-LGVSEEEADELFARLdTDGDgKISFEEFVAA 128

Acyltransferase; This family contains acyltransferases involved in phospholipid biosynthesis and other proteins of unknown function. This family also includes tafazzin, the Barth syndrome gene.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545  126 VSVKGRIASPLEAPVFVAAPHSTFFDGI--ACVVA---GLPSMVSRNENAQVPLIGRMLRAVQPILVSRVDPDSRKNTIN 200
Cdd:pfam01553   2 IEVHGLENLPRGGPAIVVANHQSYLDVLllSLALYkrgRPLVFVAKKELFDIPLVGWLMRLLGCIFIDRKNRKDAAGTLE 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 109128545  201 EIIKRTTSGGewpQILVFPEGTCTNRSCLITFKPGAFI----PGVPVQPV 246
Cdd:pfam01553  82 YLVELLREGK---LVVIFPEGTRSREGELLPFKKGAFRlaieAGVPIVPV 128

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 109128545  394 DVLRQLFALFDRNHDGSIDFREYVIGLAVLCNPAN-TEEIIQVAFKLFDVDEDGYITEEEFSTILQ 458
Cdd:pfam13499   2 EKLKEAFKLLDSDGDGYLDVEELKKLLRKLEEGEPlSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

1-acyl-sn-glycerol-3-phosphate acyltransferases; This model describes the core homologous region of a collection of related proteins, several of which are known to act as 1-acyl-sn-glycerol-3-phosphate acyltransferases (EC 2.3.1.51). Proteins scoring above the trusted cutoff are likely to have the same general activity. However, there is variation among characterized members as to whether the acyl group can be donated by acyl carrier protein or coenzyme A, and in the length and saturation of the donated acyl group. 1-acyl-sn-glycerol-3-phosphate acyltransferase is also called 1-AGP acyltransferase, lysophosphatidic acid acyltransferase, and LPA acyltransferase. [Fatty acid and phospholipid metabolism, Biosynthesis]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545  123 GFIVSVKGRIASPLEAPVFVAAPHSTFFDGIA--CVVAGLPSMVSRNENAQVPLIGRMLRAVQPILVSRvdpDSRK--NT 198
Cdd:TIGR00530   1 GLKVEVVGPENLPAKSPVLVVANHQSNLDPLTlsAAFPPPIVFIAKKELKWIPFFGIMLWLTGAIFIDR---ENIRaiAT 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 109128545  199 INEIIKRTTSGGEwpQILVFPEGTCTNRSCLITFKPGAFI----PGVPVQPVLLR 249
Cdd:TIGR00530  78 ALKAAIEVLKQGR--SIGVFPEGTRSRGRDILPFKKGAFHiaikAGVPILPVVLS 130

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 109128545 433 IQVAFKLFDVDEDGYITEEEFSTILQA-SLGVPDLDVSGLFKEI-AQGD-SISYEEF 486
Cdd:cd00051    2 LREAFRLFDKDGDGTISADELKAALKSlGEGLSEEEIDEMIREVdKDGDgKIDFEEF 58

glycerol acyltransferase family protein

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 103 RRKITQTALKFLGRAMFFSMGFIVSVKGRIASPLEAPVFVAApHSTFFDGIA-CVVAGLPSMVSRNENAQVPLIGRMLRA 181
Cdd:PLN02833 129 RKKIERKLVELICSAFVASWTGVIKYHGPRPSRRPKQVFVAN-HTSMIDFIVlEQMTPFAVIMQKHPGWVGFLQNTILES 207

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 182 VQPILVSRVDPDSRkNTINEIIKRTTSGGEWPQILVFPEGTCTNRSCLITFKPGAFIPGVPVQPVLLRYPNKLDTVTWTW 261
Cdd:PLN02833 208 VGCIWFNRTEAKDR-EVVAKKLRDHVQDPDRNPLLIFPEGTCVNNEYTVMFKKGAFELGCTVCPIAIKYNKIFVDAFWNS 286

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 109128545 262 QGYTFIQlcmlTFCQLFTK----VEVEFMPVQVPNDEEknDPVLFANKVRNVMAEALGI 316
Cdd:PLN02833 287 RKQSFTM----HLLRLMTSwavvCDVWYLEPQTLRPGE--TPIEFAERVRDMIAKRAGL 339

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 395 VLRQLFALFDRNHDGSIDFREyVIGLAVLCNPANTEEIIQVAFKLFDVDEDGYITEEEFSTILQASLGVPDLDVsgLFKE 474
Cdd:cd15898    1 WLRRQWIKADKDGDGKLSLKE-IKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLTERPELEP--IFKK 77

                         90
                 ....*....|....*..
gi 109128545 475 IA--QGDSISYEEFKSF 489
Cdd:cd15898   78 YAgtNRDYMTLEEFIRF 94

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 371 ASSSKGGRIGIDEFAKYLKL---PVSDV-LRQLFALFDRNHDGSIDFREYVIGLAVLCNPantEEIIQVaFKLFDVDEDG 446
Cdd:cd15898    9 ADKDGDGKLSLKEIKKLLKRlniRVSEKeLKKLFKEVDTNGDGTLTFDEFEELYKSLTER---PELEPI-FKKYAGTNRD 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 109128545 447 YITEEEFSTILQASLG--VPDLDVSGLFKEIA---QGDSISYEEFKSFaLRHPE 495
Cdd:cd15898   85 YMTLEEFIRFLREEQGenVSEEECEELIEKYEperENRQLSFEGFTNF-LLSPE 137

1-acyl-sn-glycerol-3-phosphate acyltransferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 121 SMGFIVSVKGR--IASPLEAPVFVAApHSTFFDGIACVVAGLP-SMVSRNENAQVPLIGRMLRAVQPILVSRVDPDSRKN 197
Cdd:PLN02901  32 SPFYKIEVEGLenLPSPDEPAVYVSN-HQSFLDIYTLFHLGRPfKFISKTSIFLIPIIGWAMYMTGHIPLKRMDRRSQLE 110

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 109128545 198 TIN---EIIKRTTSggewpqILVFPEGTCTNRSCLITFKPGAFI----PGVPVQPVLL 248
Cdd:PLN02901 111 CLKrcmELLKKGAS------VFFFPEGTRSKDGKLAAFKKGAFSvaakTGVPVVPITL 162

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 354 KLDWDG---VRKqlDEYASIASSSKGGRIGIDefakylklpvsdvLRQLFALFDRNHDGSIDFREYVIGLAVLCNPANTE 430
Cdd:NF041410  35 KLDSDGdgsVSQ--DELSSALSSKSDDGSLID-------------LSELFSDLDSDGDGSLSSDELAAAAPPPPPPPDQA 99

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 431 EIIQVAFKLF---DVDEDGYITEEEFSTILQASLGvpDLDVSGLFKEI-AQGD-SISYEEFKSfALRHPE 495
Cdd:NF041410 100 PSTELADDLLsalDTDGDGSISSDELSAGLTSAGS--SADSSQLFSALdSDGDgSVSSDELAA-ALQPPP 166

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.

                          10        20
                  ....*....|....*....|....*...
gi 109128545  432 IIQVAFKLFDVDEDGYITEEEFSTILQA 459
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKK 28

N-terminal domain of Myosin essential light chain ELC; ELC is part of the apicomplexan membrane-associated protein complex called the glideosome, which is essential for parasite motility. The glideosome is composed of six proteins: myosin A (MyoA), essential light chain ELC, myosin light chain MLC1 (also called MTIP), and the glideosome-associated proteins GAP40, GAP45, and GAP50. MyoA is a Class XIV myosin implicated in gliding motility, as well as host cell and tissue invasion by parasites. ELC binds to the MyoA neck region adjacent to the MLC1-binding site, and both myosin light chains co-located to the glideosome. Although ELCs bind to a conserved MyoA sequence, P. falciparum ELC adopts a distinct structure in the free and MyoA-bound state. Therefore ELCs enhance MyoA performance by inducing alpha helical structure formation in MyoA and thus stiffening its lever arm. It has been shown that disruption of MyoA, MLC1, or ELC have dramatic effects on parasite motility but do not affect parasite shape or replication. The ELC N-terminal domain is part of the EF-hand calcium binding motif superfamily. Calcium binding has no effect on the structure of ELCs.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 109128545 430 EEIIQVAFKLFDVDEDGYITEEEFSTILQaSLGVP--DLDVSGLfkeiaqGDSISYEEFKSFALRH 493
Cdd:cd22949    2 EEKFREAFILFDRDGDGELTMYEAVLAMR-SCGIPltNDEKDAL------PASMNWDQFENWAKKK 60

The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five EF-hand calcium-binding proteins, including several classical calpain large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14), two calpain small subunits (CAPNS1 and CAPNS2), as well as non-calpain PEF proteins, ALG-2 (apoptosis-linked gene 2, also termed programmed cell death protein 6, PDCD6), peflin, sorcin, and grancalcin. Based on the sequence similarity of EF1 hand, ALG-2 and peflin have been classified into group I PEF proteins. Calcium-dependent protease calpain subfamily members, sorcin and grancalcin, are group II PEF proteins. Calpains (EC 3.4.22.17) are calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates. They have been implicated in a number of physiological processes such as cell cycle progression, remodeling of cytoskeletal-cell membrane attachments, signal transduction, gene expression and apoptosis. ALG-2 is a pro-apoptotic factor that forms a homodimer in the cell or a heterodimer with its closest paralog peflin through their EF5s. Peflin is a 30-kD PEF protein with a longer N-terminal hydrophobic domain than any other member of the PEF family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. It exists only as a heterodimer with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. ALG-2 interacts with various proteins in a Ca2+-dependent manner. Sorcin (for soluble resistance-related calcium binding protein) is a soluble resistance-related calcium-binding protein that participates in the regulation of calcium homeostasis in cells. Grancalcin is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It plays a key role in leukocyte-specific functions that are responsible for host defense. Grancalcin can form a heterodimer together with sorcin. Members in this family contain five EF-hand motifs attached to an N-terminal region of variable length containing one or more short Gly/Pro-rich sequences. These proteins form homodimers or heterodimers through pairing between the 5th EF-hands from the two molecules. Unlike calmodulin, the PEF domains do not undergo major conformational changes upon binding Ca2+.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 296 KNDPVLFANKVRNVMAEAlGIPVTDHTY--EDCRLMISAGQLTLPMEAGLVEFTKISRKLKlDWDGVRKQLDeyasiasS 373
Cdd:cd15897   11 GDDGEISATELQQALSNV-GWTHFDLGFslETCRSMIAMMDRDHSGKLNFSEFKGLWNYIK-AWQEIFRTYD-------T 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 374 SKGGRIGIDEFAKYLKLPVSDVLRQLFAL----FDRNHdGSIDFREYVIGLAVLCNPANteeiiqvAFKLFDVDEDGYIT 449
Cdd:cd15897   82 DGSGTIDSNELRQALSGAGYRLSEQTYDIiirrYDRGR-GNIDFDDFIQCCVRLQRLTD-------AFRRYDKDQDGQIQ 153

EF-hand domain pair;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 109128545  407 HDGSIDFREYVIGLAVLCNPANTEEIIQVAFKLFDVDEDGYITEEEF 453
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEF 47

EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes alpha- and beta-parvalbumins, and a group of uncharacterized calglandulin-like proteins. Parvalbumins are small, acidic, cytosolic EF-hand-containing Ca2+-buffer and Ca2+ transporter/shuttle proteins belonging to EF-hand superfamily. They are expressed by vertebrates in fast-twitch muscle cells, specific neurons of the central and peripheral nervous system, sensory cells of the mammalian auditory organ (Corti's cell), and some other cells, and characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Thus, they may play an additional role in Mg2+ handling. Moreover, parvalbumins represent one of the major animal allergens. In metal-bound states, parvalbumins possess a rigid and stable tertiary structure and display strong allergenicity. In contrast, the metal-free parvalbumins are intrinsically disordered, and the loss of metal ions results in a conformational change that decreases their IgE binding capacity. Furthermore, parvalbumins have been widely used as a neuronal marker for a variety of functional brain systems. They also function as a Ca2+ shuttle transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus they may facilitate myocardial relaxation and play important roles in cardiac diastolic dysfunction. Parvalbumins consists of alpha- and beta- sublineages, which can be distinguished on the basis of isoelectric point (pI > 5 for alpha; pI

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 401 ALFDRNHDGSIDFREY--VIGLAvlcnpANTEEIIQVAFKLFDVDEDGYITEEEFSTILQA-SLGVPDLDVSGLFKEIAQ 477
Cdd:cd16251    7 APSAFRAHGSFNYKKFfeHVGLK-----QKSEDQIKKVFQILDKDKSGFIEEEELKYILKGfSIAGRDLTDEETKALLAA 81

                         90
                 ....*....|....*.
gi 109128545 478 GDS-----ISYEEFKS 488
Cdd:cd16251   82 GDTdgdgkIGVEEFAT 97

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 395 VLRQLFALFDRNHDGSIDFREYVIGLAVLCNPANTEEIIQVAFKLFDVDEDGYITEEEFstilqaslgvpdldvSGLFKE 474
Cdd:cd16180    1 ELRRIFQAVDRDRSGRISAKELQRALSNGDWTPFSIETVRLMINMFDRDRSGTINFDEF---------------VGLWKY 65

                         90       100       110
                 ....*....|....*....|....*....|..
gi 109128545 475 IAQ-------------GdSISYEEFKSfALRH 493
Cdd:cd16180   66 IQDwrrlfrrfdrdrsG-SIDFNELQN-ALSS 95

EF-hand domain pair;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 109128545  444 EDGYITEEEFSTILqASLGVPDL---DVSGLFKEIAQ-GD-SISYEEFKSFALR 492
Cdd:pfam13833   1 EKGVITREELKRAL-ALLGLKDLsedEVDILFREFDTdGDgYISFDEFCVLLER 53

Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family belongs to the second group of penta-EF hand (PEF) proteins. It includes classical (also called conventional or typical) calpain (referring to a calcium-dependent papain-like enzymes, EC 3.4.22.17) large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14) and two calpain small subunits (CAPNS1 and CAPNS2), which are largely confined to animals (metazoans). These PEF-containing are nonlysosomal intracellular calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates in response to calcium signalling. The classical mu- and m-calpains are heterodimers consisting of homologous but a distinct (large) L-subunit/chain (CAPN1 or CAPN2) and a common (small) S-subunit/chain (CAPNS1 or CAPNS2). These L-subunits (CAPN1 and CAPN2) and S-subunit CAPNS1 are ubiquitously found in all tissues. Other calpains likely consist of an isolated L-subunit/chain alone. Many of them, such as CAPNS2, CAPN3 (in skeletal muscle, or lens), CAPN8 (in stomach), CAPN9 (in digestive tracts), CAPN11 (in testis), CAPN12 (in follicles), are tissue-specific and have specific functions in distinct organs. The L-subunits of similar structure (called CALPA and B) also have been found in Drosophila melanogaster. The S-subunit seems to have a chaperone-like function for proper folding of the L-subunit. The catalytic L-subunits contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The S-subunits only have the PEF domain following an N-terminal Gly-rich hydrophobic domain. The calpains undergo a rearrangement of the protein backbone upon Ca2+-binding.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109128545 397 RQLFALFDRNHDGSIDFREYVIGLAVLcnpanteEIIQVAFKLFDVDEDGYITEEEFSTILQASlgvpDLDVSG-LFKEI 475
Cdd:cd16182   45 RSLIALMDTNGSGRLDLEEFKTLWSDL-------KKWQAIFKKFDTDRSGTLSSYELRKALESA----GFHLSNkVLQAL 113

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 109128545 476 AQ--GDS---ISYEEFKSFALRhpeYAKIFTTYLDLQT 508
Cdd:cd16182  114 VLryADStgrITFEDFVSCLVR---LKTAFETFSALDK 148

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 109128545 433 IQVAFKLFDVDEDGYITEEEFSTILQAslgvpdlDVSGLFKEI-AQGD-SISYEEFKSFALR------HPEYAKIF 500
Cdd:COG5126    7 LDRRFDLLDADGDGVLERDDFEALFRR-------LWATLFSEAdTDGDgRISREEFVAGMESlfeatvEPFARAAF 75

EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, MICU3, and similar proteins; This family includes mitochondrial calcium uptake protein MICU1 and its two additional paralogs, MICU2 and MICU3. MICU1 localizes to the inner mitochondrial membrane (IMM). It functions as a gatekeeper of the mitochondrial calcium uniporter (MCU) and regulates MCU-mediated mitochondrial Ca2+ uptake, which is essential for maintaining mitochondrial homoeostasis. MICU1 and MICU2 are physically associated within the uniporter complex and are co-expressed across all tissues. They may play non-redundant roles in the regulation of the mitochondrial calcium uniporter. At present, the precise molecular function of MICU2 and MICU3 remain unclear. MICU2 may play possible roles in Ca2+ sensing and regulation of MCU, calcium buffering with a secondary impact on transport or assembly and stabilization of MCU. MICU3 likely has a role in mitochondrial calcium handling. All members in this family contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.

                         10        20
                 ....*....|....*....|....*..
gi 109128545 433 IQVAFKLFDVDEDGYITEEEFSTILQA 459
Cdd:cd15900    2 FEIAFKMFDLDGDGELDKEEFNKVQSI 28