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 1985438072 125 RVMFFLMGFQ-VEVKGKVAgPLEAPILVVAPHSSFFDGIVCILAGLPSIVSRLENLSAPVFGTILRSLQPVLVSRLDPDS 203
Cdd:cd07991     2 RVLLFAFGFYvIKVHGKPD-PPEAPRIIVANHTSFIDPLILFSDLFPSIVAKKELGKLPFIGTILRALGCIFVDRSEPKD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 204 RRNTINEITKRATSGgQWPQVLIFPEGTCTNRSCLITFKQGAFIPGVPVQPVLLRYPNKLDTVTWTWQGYSFKELCVMTF 283
Cdd:cd07991    81 RKKVVEEIKERATDP-NWPPILIFPEGTTTNGKALIMFKKGAFEPGVPVQPVAIRYPNKFVDAFWNSSGYSSLMYLFRLL 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1985438072 284 CQPLTRVEVEFLPVHVPTeEEKKDPTLFASKVRNTMATALNVPVTDHTFEDCR 336
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 1985438072 125 RVMFFLMGFQ-VEVKGKVAgPLEAPILVVAPHSSFFDGIVCILAGLPSIVSRLENLSAPVFGTILRSLQPVLVSRLDPDS 203
Cdd:cd07991     2 RVLLFAFGFYvIKVHGKPD-PPEAPRIIVANHTSFIDPLILFSDLFPSIVAKKELGKLPFIGTILRALGCIFVDRSEPKD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 204 RRNTINEITKRATSGgQWPQVLIFPEGTCTNRSCLITFKQGAFIPGVPVQPVLLRYPNKLDTVTWTWQGYSFKELCVMTF 283
Cdd:cd07991    81 RKKVVEEIKERATDP-NWPPILIFPEGTTTNGKALIMFKKGAFEPGVPVQPVAIRYPNKFVDAFWNSSGYSSLMYLFRLL 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1985438072 284 CQPLTRVEVEFLPVHVPTeEEKKDPTLFASKVRNTMATALNVPVTDHTFEDCR 336
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 1985438072  149 ILVVAPHSSFFDGIVCILA-----GLPSIVSRLENLSAPVFGTILRSLQPVLVSRLDPDSRRNTINEItKRATSGGQWpq 223
Cdd:smart00563   1 ALVVANHQSFLDPLVLSALlprklGRVRFVAKKELFYVPLLGWLLRLLGAIFIDRSNGRKARAALREA-VELLKEGEW-- 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1985438072  224 VLIFPEGTCTNRSCLITFKQGAFI----PGVPVQPVLLRY 259
Cdd:smart00563  78 LLIFPEGTRSRPGKLLPFKKGAARlaleAGVPIVPVAIRG 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 1985438072 134 QVEVKGKVAGPLEAPILVVAPHSSFFDGIV--CILA---GLPSIVSRLENLSAPVFGTILRSLQPVLVSRLDPDSRRNTI 208
Cdd:pfam01553   1 RIEVHGLENLPRGGPAIVVANHQSYLDVLLlsLALYkrgRPLVFVAKKELFDIPLVGWLMRLLGCIFIDRKNRKDAAGTL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1985438072 209 NEITKRATSGGQwpqVLIFPEGTCTNRSCLITFKQGAFI----PGVPVQPV 255
Cdd:pfam01553  81 EYLVELLREGKL---VVIFPEGTRSREGELLPFKKGAFRlaieAGVPIVPV 128

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1985438072 439 EETIQMAFNLFDVDDDGSITEEEFACILRS-SLGVP--DLDVSQLFKEIDTDHSGKIAYNEFKDFA 501
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKlEEGEPlsDEEVEELFKEFDLDKDGRISFEEFLELY 66

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 1985438072 132 GFQVEVKGKVAGPLEAPILVVAPHSSFFDgIVCILAGLP---SIVSRLENLSAPVFGTILRSLQPVLVSRldpDSRR--N 206
Cdd:TIGR00530   1 GLKVEVVGPENLPAKSPVLVVANHQSNLD-PLTLSAAFPppiVFIAKKELKWIPFFGIMLWLTGAIFIDR---ENIRaiA 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1985438072 207 TINEITKRATSGGQwpQVLIFPEGTCTNRSCLITFKQGAFI----PGVPVQPVLLR 258
Cdd:TIGR00530  77 TALKAAIEVLKQGR--SIGVFPEGTRSRGRDILPFKKGAFHiaikAGVPILPVVLS 130

XopAW family type III secretion system calcium-binding effector;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 405 LKELFLLFDRNGDGTIDFREyvigL-SVLCNPANTEETIQMA--FNLFDVDDDGSITEEEFACIL-----RSSLGVPDLD 476
Cdd:NF041410   29 QKQLFAKLDSDGDGSVSQDE----LsSALSSKSDDGSLIDLSelFSDLDSDGDGSLSSDELAAAApppppPPDQAPSTEL 104

                          90       100
                  ....*....|....*....|.
gi 1985438072 477 VSQLFKEIDTDHSGKIAYNEF 497
Cdd:NF041410  105 ADDLLSALDTDGDGSISSDEL 125

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 1985438072  405 LKELFLLFDRNGDGTIDFREYVIGLS 430
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDLLK 27

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 1985438072 125 RVMFFLMGFQ-VEVKGKVAgPLEAPILVVAPHSSFFDGIVCILAGLPSIVSRLENLSAPVFGTILRSLQPVLVSRLDPDS 203
Cdd:cd07991     2 RVLLFAFGFYvIKVHGKPD-PPEAPRIIVANHTSFIDPLILFSDLFPSIVAKKELGKLPFIGTILRALGCIFVDRSEPKD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 204 RRNTINEITKRATSGgQWPQVLIFPEGTCTNRSCLITFKQGAFIPGVPVQPVLLRYPNKLDTVTWTWQGYSFKELCVMTF 283
Cdd:cd07991    81 RKKVVEEIKERATDP-NWPPILIFPEGTTTNGKALIMFKKGAFEPGVPVQPVAIRYPNKFVDAFWNSSGYSSLMYLFRLL 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1985438072 284 CQPLTRVEVEFLPVHVPTeEEKKDPTLFASKVRNTMATALNVPVTDHTFEDCR 336
Cdd:cd07991   160 TQPANVLEVEFLPVYTPS-EEGEDPKEFANRVRLIMANKLGLPATDWTGEDKR 211

Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-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 1-acyl-sn-glycerol-3-phosphate acyltransferase (AGPAT, PlsC), Tafazzin (product of Barth syndrome gene), and similar proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 125 RVMFFLMGFQVEVKGKVAGPLEAPILVVAPHSSFFDGIVCILAGLPSI--VSRLENLSAPVFGTILRSLQPVLVSRLDPD 202
Cdd:cd07989     2 RLLLRLLGVRVRVEGLENLPPKGPVIIVANHQSYLDPLVLGAALPRPIrfVAKKELFKIPFLGWLLRLLGAIPIDRGNGR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 203 SRRNTINEITKRATSGGqwpQVLIFPEGTCTNRSCLITFKQGAFI----PGVPVQPVLLRYPNKLdtvtWTWQGYSFKEl 278
Cdd:cd07989    82 SAREALREAIEALKEGE---SVVIFPEGTRSRDGELLPFKSGAFRlakeAGVPIVPVAISGTWGS----LPKGKKLPRP- 153

                         170       180
                  ....*....|....*....|....*....
gi 1985438072 279 cvmtfcqplTRVEVEFLPVHVPTEEEKKD 307
Cdd:cd07989   154 ---------GRVTVRIGEPIPPEGLELAE 173

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 368 PIRDQLDTFAAIAnASKGGRIGMEEFAEYLklpvSDVLKELFLLFDRNGDGTIDFREYVIGLSVLCNPANtEETIQMAFN 447
Cdd:COG5126     3 QRRKLDRRFDLLD-ADGDGVLERDDFEALF----RRLWATLFSEADTDGDGRISREEFVAGMESLFEATV-EPFARAAFD 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1985438072 448 LFDVDDDGSITEEEFAcILRSSLGVPDLDVSQLFKEIDTDHSGKIAYNEFKDF--AFKHPE 506
Cdd:COG5126    77 LLDTDGDGKISADEFR-RLLTALGVSEEEADELFARLDTDGDGKISFEEFVAAvrDYYTPD 136

Lysophospholipid acyltransferases (LPLATs) of glycerophospholipid biosynthesis; Lysophospholipid acyltransferase (LPLAT) superfamily members are acyltransferases of de novo and remodeling pathways of glycerophospholipid biosynthesis. These proteins 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 superfamily are LPLATs such as glycerol-3-phosphate 1-acyltransferase (GPAT, PlsB), 1-acyl-sn-glycerol-3-phosphate acyltransferase (AGPAT, PlsC), lysophosphatidylcholine acyltransferase 1 (LPCAT-1), lysophosphatidylethanolamine acyltransferase (LPEAT, also known as, MBOAT2, membrane-bound O-acyltransferase domain-containing protein 2), lipid A biosynthesis lauroyl/myristoyl acyltransferase, 2-acylglycerol O-acyltransferase (MGAT), dihydroxyacetone phosphate acyltransferase (DHAPAT, also known as 1 glycerol-3-phosphate O-acyltransferase 1) and Tafazzin (the protein product of the Barth syndrome (TAZ) gene).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 129 FLMGFQVEVKGKVAGPLEAPILVVAPHSSFFDGIVCILAGLPS-------IVSRLENLSAPVFGTilrsLQPVLVSRLDP 201
Cdd:cd06551     8 FFGFVRLEVKGPPPPPGGGPVLFVSNHSSWWDGLILFLLLERGlrrdvygLMDEELLERYPFFTR----LGAFSVDRDSP 83

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1985438072 202 DSRRNTINEITKRATSGGQWpqVLIFPEGTCTNRS-CLITFKQGAFIP----GVPVQPVLLRYPN 261
Cdd:cd06551    84 RSAAKSLKYVARLLSKPGSV--VWIFPEGTRTRRDkRPLQFKPGVAHLaekaGVPIVPVALRYTF 146

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1985438072 439 EETIQMAFNLFDVDDDGSITEEEFACILRS-SLGVP--DLDVSQLFKEIDTDHSGKIAYNEFKDFA 501
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKlEEGEPlsDEEVEELFKEFDLDKDGRISFEEFLELY 66

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 1985438072 404 VLKELFLLFDRNGDGTIDFREYVIGLSVLCNPANTEETIQMAFNLFDVDDDGSITEEEFaCILRSSLGvpdlDVSQLFKE 483
Cdd:cd16180     1 ELRRIFQAVDRDRSGRISAKELQRALSNGDWTPFSIETVRLMINMFDRDRSGTINFDEF-VGLWKYIQ----DWRRLFRR 75

                          90
                  ....*....|....*.
gi 1985438072 484 IDTDHSGKIAYNEFKD 499
Cdd:cd16180    76 FDRDRSGSIDFNELQN 91

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 1985438072 132 GFQVEVKGKVAGPLEAPILVVAPHSSFFDgIVCILAGLP---SIVSRLENLSAPVFGTILRSLQPVLVSRldpDSRR--N 206
Cdd:TIGR00530   1 GLKVEVVGPENLPAKSPVLVVANHQSNLD-PLTLSAAFPppiVFIAKKELKWIPFFGIMLWLTGAIFIDR---ENIRaiA 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1985438072 207 TINEITKRATSGGQwpQVLIFPEGTCTNRSCLITFKQGAFI----PGVPVQPVLLR 258
Cdd:TIGR00530  77 TALKAAIEVLKQGR--SIGVFPEGTRSRGRDILPFKKGAFHiaikAGVPILPVVLS 130

centrin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 369 IRDQLDTFaaiaNASKGGRIGMEEFAEYLKL----PVSDVLKELFLLFDRNGDGTIDFREYVIGLSVLCNPANTEETIQM 444
Cdd:PTZ00183   19 IREAFDLF----DTDGSGTIDPKELKVAMRSlgfePKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKLGERDPREEILK 94

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1985438072 445 AFNLFDVDDDGSITEEEFACILRsSLG--VPDLDVSQLFKEIDTDHSGKIAYNEFK 498
Cdd:PTZ00183   95 AFRLFDDDKTGKISLKNLKRVAK-ELGetITDEELQEMIDEADRNGDGEISEEEFY 149

calmodulin; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1985438072 438 TEETIQM---AFNLFDVDDDGSITEEEFACILRsSLGV--PDLDVSQLFKEIDTDHSGKIAYNEF 497
Cdd:PTZ00184    6 TEEQIAEfkeAFSLFDKDGDGTITTKELGTVMR-SLGQnpTEAELQDMINEVDADGNGTIDFPEF 69

EF-hand domain pair;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1985438072 453 DDGSITEEEFACILRSsLGVPDL---DVSQLFKEIDTDHSGKIAYNEFKDFAFK 503
Cdd:pfam13833   1 EKGVITREELKRALAL-LGLKDLsedEVDILFREFDTDGDGYISFDEFCVLLER 53

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 1985438072 442 IQMAFNLFDVDDDGSITEEEFACILRS-SLGVPDLDVSQLFKEIDTDHSGKIAYNEFKDF---AFKHPEYAKLFTTYLEL 517
Cdd:cd15898     2 LRRQWIKADKDGDGKLSLKEIKKLLKRlNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELyksLTERPELEPIFKKYAGT 81

                          90
                  ....*....|....*
gi 1985438072 518 QRcqlQTLDEEDYQT 532
Cdd:cd15898    82 NR---DYMTLEEFIR 93

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 1985438072 404 VLKELFLLFDRNGDGTIDFREyVIGLSVLCNPANTEETIQMAFNLFDVDDDGSITEEEFACILRSSLGVPDLDvsQLFKE 483
Cdd:cd15898     1 WLRRQWIKADKDGDGKLSLKE-IKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLTERPELE--PIFKK 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1985438072 484 IDTDHSGKIAYNEFKDFafkhpeyaklfttyleLQRCQLQTLDEED 529
Cdd:cd15898    78 YAGTNRDYMTLEEFIRF----------------LREEQGENVSEEE 107

EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and similar proteins; CBN, the product of the cbn gene, is a Drosophila homolog to vertebrate neuronal six EF-hand calcium binding proteins. It is expressed through most of ontogenesis with a selective distribution in the nervous system and in a few small adult thoracic muscles. Its precise biological role remains unclear. CBN contains six EF-hand motifs, but some of them may not bind calcium ions due to the lack of key residues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 411 LFDRNGDGTIDFREYVIGLSV----LCNPAN------TEETIQMAFNLFDVDDDGSITEEEFACILRS--SLGVPDLDVS 478
Cdd:cd16179   149 LFDRNKDGKLQLSEMARLLPVkenfLCRPIFkgagklTREDIDRVFALYDRDNNGTIENEELTGFLKDllELVQEDYDEQ 228

                          90       100
                  ....*....|....*....|....*....
gi 1985438072 479 QL--FKEI-----DTDHSGKIAYNEFKDF 500
Cdd:cd16179   229 DLeeFKEIilrgwDFNNDGKISRKELTML 257

XopAW family type III secretion system calcium-binding effector;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 405 LKELFLLFDRNGDGTIDFREyvigL-SVLCNPANTEETIQMA--FNLFDVDDDGSITEEEFACIL-----RSSLGVPDLD 476
Cdd:NF041410   29 QKQLFAKLDSDGDGSVSQDE----LsSALSSKSDDGSLIDLSelFSDLDSDGDGSLSSDELAAAApppppPPDQAPSTEL 104

                          90       100
                  ....*....|....*....|.
gi 1985438072 477 VSQLFKEIDTDHSGKIAYNEF 497
Cdd:NF041410  105 ADDLLSALDTDGDGSISSDEL 125

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain 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 C-terminal C2 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. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 405 LKELFLLFDRNGDGTIDFREYVIGLSVLcNPANTEETIQMAFNLFDVDDDGSITEEEFACILRSSLGVPDLDvsQLFKEI 484
Cdd:cd16202     2 LKDQFRKADKNGDGKLSFKECKKLLKKL-NVKVDKDYAKKLFQEADTSGEDVLDEEEFVQFYNRLTKRPEIE--ELFKKY 78

                          90
                  ....*....|....*.
gi 1985438072 485 dTDHSGKIAYNEFKDF 500
Cdd:cd16202    79 -SGDDEALTVEELRRF 93

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 1985438072 380 ANASKGGRIGMEEFAEYLKL---PVSDV-LKELFLLFDRNGDGTIDFREYVIGLSVLCNPantEEtIQMAFNLFDVDDDG 455
Cdd:cd15898     9 ADKDGDGKLSLKEIKKLLKRlniRVSEKeLKKLFKEVDTNGDGTLTFDEFEELYKSLTER---PE-LEPIFKKYAGTNRD 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1985438072 456 SITEEEFACILRSSLG--VPDLDVSQLFKEIDTD-HSGKIAYNEFKDF 500
Cdd:cd15898    85 YMTLEEFIRFLREEQGenVSEEECEELIEKYEPErENRQLSFEGFTNF 132

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 1985438072 439 EETIQMAFNLFDVDDDGSITEEEFACILRsSLGVPdldVSQlfKEIDtDHSGKIAYNEFKDFAFKH 504
Cdd:cd22949     2 EEKFREAFILFDRDGDGELTMYEAVLAMR-SCGIP---LTN--DEKD-ALPASMNWDQFENWAKKK 60

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1985438072 438 TEETIQMAFNLFDVDDDGSITEEEFACILRS-SLGVPDL---DVSQLFKEIDTDHSGKIAYNEF 497
Cdd:cd16251    32 SEDQIKKVFQILDKDKSGFIEEEELKYILKGfSIAGRDLtdeETKALLAAGDTDGDGKIGVEEF 95

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985438072 391 EEFAEylkLPVSDVLKELFLLF---DRNGDGTIDFREY----VIGLSVLcnpanTEETIQMAFNLFDVDDDGSITEEEfa 463
Cdd:cd16227    24 EEFDE---LPPEEAKRRLAVLAkkmDLNDDGFIDRKELkawiLRSFKML-----DEEEANERFEEADEDGDGKVTWEE-- 93