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 528485410  98 RMYFFGMGFKVV-VKGKKASTlEAPILAVAPHSSFFDAIACIESGLPSTVSRIESLEAPIFGRFLRCVQPVLVSRTDPDS 176
Cdd:cd07991    2 RVLLFAFGFYVIkVHGKPDPP-EAPRIIVANHTSFIDPLILFSDLFPSIVAKKELGKLPFIGTILRALGCIFVDRSEPKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 177 RRNTIIEIERRAKSaGHWPQVLIFPEGTCTNRSCLITFKQGGFVPGVPVQPVLIRYPNKLDTVTWTWQGPKSARLLLLTL 256
Cdd:cd07991   81 RKKVVEEIKERATD-PNWPPILIFPEGTTTNGKALIMFKKGAFEPGVPVQPVAIRYPNKFVDAFWNSSGYSSLMYLFRLL 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 528485410 257 CQLCTTVEVEFLPPQVPTEmEKKCPLKFAQSVRAVMAKSLKLPVTDHTYEDCR 309
Cdd:cd07991  160 TQPANVLEVEFLPVYTPSE-EGEDPKEFANRVRLIMANKLGLPATDWTGEDKR 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 528485410  98 RMYFFGMGFKVV-VKGKKASTlEAPILAVAPHSSFFDAIACIESGLPSTVSRIESLEAPIFGRFLRCVQPVLVSRTDPDS 176
Cdd:cd07991    2 RVLLFAFGFYVIkVHGKPDPP-EAPRIIVANHTSFIDPLILFSDLFPSIVAKKELGKLPFIGTILRALGCIFVDRSEPKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 177 RRNTIIEIERRAKSaGHWPQVLIFPEGTCTNRSCLITFKQGGFVPGVPVQPVLIRYPNKLDTVTWTWQGPKSARLLLLTL 256
Cdd:cd07991   81 RKKVVEEIKERATD-PNWPPILIFPEGTTTNGKALIMFKKGAFEPGVPVQPVAIRYPNKFVDAFWNSSGYSSLMYLFRLL 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 528485410 257 CQLCTTVEVEFLPPQVPTEmEKKCPLKFAQSVRAVMAKSLKLPVTDHTYEDCR 309
Cdd:cd07991  160 TQPANVLEVEFLPVYTPSE-EGEDPKEFANRVRLIMANKLGLPATDWTGEDKR 211

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 359 GRITVEEFASFLklpiSPALQQLFALFDRNGDGTIDFREYVIGVTVLCRPANnEEVIQTAFKLFDIDEDNCITQEEFSSL 438
Cdd:COG5126   20 GVLERDDFEALF----RRLWATLFSEADTDGDGRISREEFVAGMESLFEATV-EPFARAAFDLLDTDGDGKISADEFRRL 94

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 528485410 439 LRsALGVCDLDVHSLFREIDADGSGHITYDEFRSF 473
Cdd:COG5126   95 LT-ALGVSEEEADELFARLDTDGDGKISFEEFVAA 128

calmodulin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 359 GRITVEEFASFLKL----PISPALQQLFALFDRNGDGTIDFREYVIGVTVLCRPANNEEVIQTAFKLFDIDEDNCITQEE 434
Cdd:PTZ00184  26 GTITTKELGTVMRSlgqnPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKDTDSEEEIKEAFKVFDRDGNGFISAAE 105

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 528485410 435 FSSLLRSaLG--VCDLDVHSLFREIDADGSGHITYDEF 470
Cdd:PTZ00184 106 LRHVMTN-LGekLTDEEVDEMIREADVDGDGQINYEEF 142

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 528485410 418 AFKLFDIDEDNCITQEEFSSLLRSA-LGVCDLDVHSLFREIDADGSGHITYDEFRSF 473
Cdd:cd00051    5 AFRLFDKDGDGTISADELKAALKSLgEGLSEEEIDEMIREVDKDGDGKIDFEEFLEL 61

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 528485410  105 GFKVVVKGKKASTLEAPILAVAPHSSFFDAIAcIESGLP---STVSRIESLEAPIFGRFLRCVQPVLVSRtdpDSRR--N 179
Cdd:TIGR00530   1 GLKVEVVGPENLPAKSPVLVVANHQSNLDPLT-LSAAFPppiVFIAKKELKWIPFFGIMLWLTGAIFIDR---ENIRaiA 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 528485410  180 TIIEIERRAKSAGhWPqVLIFPEGTCTNRSCLITFKQGGFV----PGVPVQPVLIR 231
Cdd:TIGR00530  77 TALKAAIEVLKQG-RS-IGVFPEGTRSRGRDILPFKKGAFHiaikAGVPILPVVLS 130

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 378 LQQLFALFDRNGDGTIDFREYVIGVTVLCRPANNEEVIQTAFKLF---DIDEDNCITQEEFSSLLRSALGvcDLDVHSLF 454
Cdd:NF041410  65 LSELFSDLDSDGDGSLSSDELAAAAPPPPPPPDQAPSTELADDLLsalDTDGDGSISSDELSAGLTSAGS--SADSSQLF 142

                         90
                 ....*....|....*.
gi 528485410 455 REIDADGSGHITYDEF 470
Cdd:NF041410 143 SALDSDGDGSVSSDEL 158

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 528485410   378 LQQLFALFDRNGDGTIDFREYVIGVT 403
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 528485410  98 RMYFFGMGFKVV-VKGKKASTlEAPILAVAPHSSFFDAIACIESGLPSTVSRIESLEAPIFGRFLRCVQPVLVSRTDPDS 176
Cdd:cd07991    2 RVLLFAFGFYVIkVHGKPDPP-EAPRIIVANHTSFIDPLILFSDLFPSIVAKKELGKLPFIGTILRALGCIFVDRSEPKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 177 RRNTIIEIERRAKSaGHWPQVLIFPEGTCTNRSCLITFKQGGFVPGVPVQPVLIRYPNKLDTVTWTWQGPKSARLLLLTL 256
Cdd:cd07991   81 RKKVVEEIKERATD-PNWPPILIFPEGTTTNGKALIMFKKGAFEPGVPVQPVAIRYPNKFVDAFWNSSGYSSLMYLFRLL 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 528485410 257 CQLCTTVEVEFLPPQVPTEmEKKCPLKFAQSVRAVMAKSLKLPVTDHTYEDCR 309
Cdd:cd07991  160 TQPANVLEVEFLPVYTPSE-EGEDPKEFANRVRLIMANKLGLPATDWTGEDKR 211

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 359 GRITVEEFASFLklpiSPALQQLFALFDRNGDGTIDFREYVIGVTVLCRPANnEEVIQTAFKLFDIDEDNCITQEEFSSL 438
Cdd:COG5126   20 GVLERDDFEALF----RRLWATLFSEADTDGDGRISREEFVAGMESLFEATV-EPFARAAFDLLDTDGDGKISADEFRRL 94

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 528485410 439 LRsALGVCDLDVHSLFREIDADGSGHITYDEFRSF 473
Cdd:COG5126   95 LT-ALGVSEEEADELFARLDTDGDGKISFEEFVAA 128

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 528485410   125 VAPHSSFFDAI--ACI---ESGLPSTVSRIESLEAPIFGRFLRCVQPVLVSRTDPDSRRNTIIEIERRAKSaGHWpqVLI 199
Cdd:smart00563   4 VANHQSFLDPLvlSALlprKLGRVRFVAKKELFYVPLLGWLLRLLGAIFIDRSNGRKARAALREAVELLKE-GEW--LLI 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 528485410   200 FPEGTCTNRSCLITFKQGGF----VPGVPVQPVLIRY 232
Cdd:smart00563  81 FPEGTRSRPGKLLPFKKGAArlalEAGVPIVPVAIRG 117

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 359 GRITVEEFASFLKLP----ISPALQQLFALFDRNGDGTIDFREYVigvTVLCRPANNEEVIQTAFKLFDIDEDNCITQEE 434
Cdd:COG5126   48 GRISREEFVAGMESLfeatVEPFARAAFDLLDTDGDGKISADEFR---RLLTALGVSEEEADELFARLDTDGDGKISFEE 124

                 ....*..
gi 528485410 435 FSSLLRS 441
Cdd:COG5126  125 FVAAVRD 131

centrin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 340 DNVKKEL-ESFaNIACSCKGGRITVEEFASFLKL----PISPALQQLFALFDRNGDGTIDFREYVIGVTVLCRPANNEEV 414
Cdd:PTZ00183  13 EDQKKEIrEAF-DLFDTDGSGTIDPKELKVAMRSlgfePKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKLGERDPREE 91

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 415 IQTAFKLFDIDEDNCITqeeFSSLLRSA--LG--VCDLDVHSLFREIDADGSGHITYDEF 470
Cdd:PTZ00183  92 ILKAFRLFDDDKTGKIS---LKNLKRVAkeLGetITDEELQEMIDEADRNGDGEISEEEF 148

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 528485410 418 AFKLFDIDEDNCITQEEFSSLLRSA-LGVCDLDVHSLFREIDADGSGHITYDEFRSF 473
Cdd:cd00051    5 AFRLFDKDGDGTISADELKAALKSLgEGLSEEEIDEMIREVDKDGDGKIDFEEFLEL 61

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 528485410  107 KVVVKGKKASTLEAPILAVAPHSSFFDAI--ACI---ESGLPSTVSRIESLEAPIFGRFLRCVQPVLVSRTDPDSRRNTI 181
Cdd:pfam01553   1 RIEVHGLENLPRGGPAIVVANHQSYLDVLllSLAlykRGRPLVFVAKKELFDIPLVGWLMRLLGCIFIDRKNRKDAAGTL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 528485410  182 IEIERRAKSAGhwpQVLIFPEGTCTNRSCLITFKQGGF----VPGVPVQPVLI 230
Cdd:pfam01553  81 EYLVELLREGK---LVVIFPEGTRSREGELLPFKKGAFrlaiEAGVPIVPVAI 130

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 528485410 378 LQQLFALFDRNGDGTIDFREyvigVTVLCRPAN---NEEVIQTAFKLFDIDEDNCITQEEFSSLLRSALGVCDLDvhSLF 454
Cdd:cd15898    2 LRRQWIKADKDGDGKLSLKE----IKKLLKRLNirvSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLTERPELE--PIF 75

                         90
                 ....*....|....*....
gi 528485410 455 REIDADGSGHITYDEFRSF 473
Cdd:cd15898   76 KKYAGTNRDYMTLEEFIRF 94

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 357 KGGRITVEEFASFLKLP-----ISPAlQQLFALFDRNGDGTIDFREYVigvtVLCRPANNeevIQTAFKLFDIDEDNCIT 431
Cdd:cd16185   13 RSGSIDVNELQKALAGGgllfsLATA-EKLIRMFDRDGNGTIDFEEFA----ALHQFLSN---MQNGFEQRDTSRSGRLD 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 528485410 432 QEE-FSSLLRSALGVCDLDVHSLFREIDADGSGHITYDEF 470
Cdd:cd16185   85 ANEvHEALAASGFQLDPPAFQALFRKFDPDRGGSLGFDDY 124

Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: Unknown AAK14816-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 uncharacterized glycerol-3-phosphate acyltransferases such as the Plasmodium falciparum locus AAK14816 putative acyltransferase, and similar proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410  86 RFLHRRVMTFlgrmyFFGmgfKVVVKGKKASTLEAPILAVAPHS-SFFDA--IACIESGLPSTVSRIESLEAPIFGRFLR 162
Cdd:cd07992    2 RLLSRVILRI-----YFR---RITVVGRENVPKDGPVIFLGNHPnALIDPllLAATLRRPVRFLAKADLFKNPLIGWLLE 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 163 CVQPVLVSRtDPDSRRNTIIEIE--------RRAKSAGHWpqVLIFPEGTCTNRSCLITFKQG----------GFVPGVP 224
Cdd:cd07992   74 SFGAIPVYR-PKDLARGGIGKISnaavfdavGEALKAGGA--IGIFPEGGSHDRPRLLPLKAGaarmalealeAGQKDVK 150

                        170
                 ....*....|.
gi 528485410 225 VQPVLIRYPNK 235
Cdd:cd07992  151 IVPVGLNYEDK 161

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 528485410 377 ALQQLFALFDRNGDGTIDFREYVIGVTVLCRPANNEEVIQTAFKLFDIDEDNCITQEEFSSLLRsalgvCDLDVHSLFRE 456
Cdd:cd16180    1 ELRRIFQAVDRDRSGRISAKELQRALSNGDWTPFSIETVRLMINMFDRDRSGTINFDEFVGLWK-----YIQDWRRLFRR 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528485410 457 IDADGSGHITYDEFRS------FALNHPEYAKLFTTYIELQRyQGLQgdetdFDSaFSHCCT 512
Cdd:cd16180   76 FDRDRSGSIDFNELQNalssfgYRLSPQFVQLLVRKFDRRRR-GSIS-----FDD-FVEACV 130

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 528485410 359 GRITVEEFASFLKL----PISPA-LQQLFALFDRNGDGTIDFREYVigvtvlcrpanneEVI------QTAFKLFDIDED 427
Cdd:cd16180   15 GRISAKELQRALSNgdwtPFSIEtVRLMINMFDRDRSGTINFDEFV-------------GLWkyiqdwRRLFRRFDRDRS 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 528485410 428 NCITQEEFSSLLRSaLGvCDLD---VHSLFREIDADGSGHITYDEF 470
Cdd:cd16180   82 GSIDFNELQNALSS-FG-YRLSpqfVQLLVRKFDRRRRGSISFDDF 125

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 378 LQQLFALFDRNGDGTIDFREYVIGVTVLCRPANNEEVIQTAFKLF---DIDEDNCITQEEFSSLLRSALGvcDLDVHSLF 454
Cdd:NF041410  65 LSELFSDLDSDGDGSLSSDELAAAAPPPPPPPDQAPSTELADDLLsalDTDGDGSISSDELSAGLTSAGS--SADSSQLF 142

                         90
                 ....*....|....*.
gi 528485410 455 REIDADGSGHITYDEF 470
Cdd:NF041410 143 SALDSDGDGSVSSDEL 158

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
                 ....*....|....*....|....*....|....*....|....*....
gi 528485410 359 GRITVEEFASFLKL----PISPALQQLFALFDRNGDGTIDFREYVIGVT 403
Cdd:cd00051   15 GTISADELKAALKSlgegLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

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 528485410 359 GRITVEEFAS---FLKlpispALQQLFALFDRNGDGTIDFREYV-----IGVTVlcrpanNEEVIQTAFKLFDIDEDNCI 430
Cdd:cd16180   52 GTINFDEFVGlwkYIQ-----DWRRLFRRFDRDRSGSIDFNELQnalssFGYRL------SPQFVQLLVRKFDRRRRGSI 120

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 528485410 431 TqeeFSSLLRSALGVCDL-DVhslFREIDADGSGHIT--YDEF 470
Cdd:cd16180  121 S---FDDFVEACVTLKRLtDA---FRKYDTNRTGYATisYEDF 157

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 378 LQQLFALFDRNGDGTIDFREYvigVTVLCRPANNEEVIQTA--FKLFDIDEDNCITQEEFSSLL-----RSALGVCDLDV 450
Cdd:NF041410  29 QKQLFAKLDSDGDGSVSQDEL---SSALSSKSDDGSLIDLSelFSDLDSDGDGSLSSDELAAAApppppPPDQAPSTELA 105

                         90       100
                 ....*....|....*....|..
gi 528485410 451 HSLFREIDADGSGHITYDEFRS 472
Cdd:NF041410 106 DDLLSALDTDGDGSISSDELSA 127

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 528485410 359 GRITVEEFASFLKL---PISPA-LQQLFALFDRNGDGTIDFREYVigvtVLCRPANNEEVIQTAFKLFDIDEDNCITQEE 434
Cdd:cd15898   15 GKLSLKEIKKLLKRlniRVSEKeLKKLFKEVDTNGDGTLTFDEFE----ELYKSLTERPELEPIFKKYAGTNRDYMTLEE 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 528485410 435 FSSLLRSALGVC--DLDVHSLFREIDADGSGH-ITYDEFRSF 473
Cdd:cd15898   91 FIRFLREEQGENvsEEECEELIEKYEPERENRqLSFEGFTNF 132

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 528485410 358 GGRITVEEFAsflKLPISPA---LQQLFALFDRNGDGTIDFREYVIGVTVLCRPANNEEVIQTaFKLFDIDEDNCITQEE 434
Cdd:cd16227   18 GSRKEAEEFD---ELPPEEAkrrLAVLAKKMDLNDDGFIDRKELKAWILRSFKMLDEEEANER-FEEADEDGDGKVTWEE 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528485410 435 FsslLRSALGVCDLDVHS------------------LFREIDADGSGHITYDEFRSFAlnHPE-YAKLFTTYIElqryQG 495
Cdd:cd16227   94 Y---LADSFGYDDEDNEEmikdsteddlklleddkeMFEAADLNKDGKLDKTEFSAFQ--HPEeYPHMHPVLIE----QT 164

                        170       180       190
                 ....*....|....*....|....*....|....
gi 528485410 496 LQGDETDFDSAFShcctaaYDEYQEDSASDKKDD 529
Cdd:cd16227  165 LRDKDKDNDGFIS------FQEFLGDRAGHEDKE 192

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 528485410   378 LQQLFALFDRNGDGTIDFREYVIGVT 403
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDLLK 27