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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398  48 LSRSFRVMDDDGSKSLSPEEFKKGVTDIgldltdseIDEMFSRFDTDGSGNINMTEFLVKLRPPMNNSRISIIEKAFDKM 127
Cdd:COG5126   7 LDRRFDLLDADGDGVLERDDFEALFRRL--------WATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLL 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24646398 128 DANGDGQITVTDLKNVYSVRDHPKYLSGEMtenqiftqflknFEVGAPNPDGIVTREEF 186
Cdd:COG5126  79 DTDGDGKISADEFRRLLTALGVSEEEADEL------------FARLDTDGDGKISFEEF 125

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398  48 LSRSFRVMDDDGSKSLSPEEFKKGVTDIgldltdseIDEMFSRFDTDGSGNINMTEFLVKLRPPMNNSRISIIEKAFDKM 127
Cdd:COG5126   7 LDRRFDLLDADGDGVLERDDFEALFRRL--------WATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLL 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24646398 128 DANGDGQITVTDLKNVYSVRDHPKYLSGEMtenqiftqflknFEVGAPNPDGIVTREEF 186
Cdd:COG5126  79 DTDGDGKISADEFRRLLTALGVSEEEADEL------------FARLDTDGDGKISFEEF 125

centrin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398   52 FRVMDDDGSKSLSPEEFKKGVTDIGLDLTDSEIDEMFSRFDTDGSGNINMTEFLVKLRPPMNN--SRISIIeKAFDKMDA 129
Cdd:PTZ00183  23 FDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKLGErdPREEIL-KAFRLFDD 101

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 24646398  130 NGDGQITVTDLKNVysvrdhpkylSGEMTENQIFTQFLKNFEVGAPNPDGIVTREEFIN 188
Cdd:PTZ00183 102 DKTGKISLKNLKRV----------AKELGETITDEELQEMIDEADRNGDGEISEEEFYR 150

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398   52 FRVMDDDGSKSLSPEEFKKGVTDIGLDLTDSEIDEMFSRFDTDGSGNINMTEFLVKLRPP----MNNSRISIIEKAFDKM 127
Cdd:NF041410  33 FAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAPPPppppDQAPSTELADDLLSAL 112

                         90
                 ....*....|...
gi 24646398  128 DANGDGQITVTDL 140
Cdd:NF041410 113 DTDGDGSISSDEL 125

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398   52 FRVMDDDGSKSLSPEEFKKGVTDIGlDLTDSEidEMFSRFDTDGSGNINMTEFLVKLRPP 111
Cdd:NF041410 109 LSALDTDGDGSISSDELSAGLTSAG-SSADSS--QLFSALDSDGDGSVSSDELAAALQPP 165

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 24646398     83 EIDEMFSRFDTDGSGNINMTEFLVKLR 109
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLK 27

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398  48 LSRSFRVMDDDGSKSLSPEEFKKGVTDIgldltdseIDEMFSRFDTDGSGNINMTEFLVKLRPPMNNSRISIIEKAFDKM 127
Cdd:COG5126   7 LDRRFDLLDADGDGVLERDDFEALFRRL--------WATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLL 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24646398 128 DANGDGQITVTDLKNVYSVRDHPKYLSGEMtenqiftqflknFEVGAPNPDGIVTREEF 186
Cdd:COG5126  79 DTDGDGKISADEFRRLLTALGVSEEEADEL------------FARLDTDGDGKISFEEF 125

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 24646398  48 LSRSFRVMDDDGSKSLSPEEFKKGVTDIGLDLTDSEIDEMFSRFDTDGSGNINMTEFL 105
Cdd:cd00051   2 LREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFL 59

calmodulin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398   51 SFRVMDDDGSKSLSPEEFKKGVTDIGLDLTDSEIDEMFSRFDTDGSGNINMTEFLVKLRPPM--NNSRISIIEkAFDKMD 128
Cdd:PTZ00184  16 AFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMkdTDSEEEIKE-AFKVFD 94

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 24646398  129 ANGDGQITVTDLKNVYSVRdhpkylsGEMTENQIFTQFLKNFEVgapNPDGIVTREEFI 187
Cdd:PTZ00184  95 RDGNGFISAAELRHVMTNL-------GEKLTDEEVDEMIREADV---DGDGQINYEEFV 143

EF-hand domain pair;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 24646398    50 RSFRVMDDDGSKSLSPEEFKKGVT--DIGLDLTDSEIDEMFSRFDTDGSGNINMTEFL 105
Cdd:pfam13499   6 EAFKLLDSDGDGYLDVEELKKLLRklEEGEPLSDEEVEELFKEFDLDKDGRISFEEFL 63

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 24646398  83 EIDEMFSRFDTDGSGNINMTEF---LVKLRPPMNnsrISIIEKAFDKMDANGDGQIT 136
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELkaaLKSLGEGLS---EEEIDEMIREVDKDGDGKID 54

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398   52 FRVMDDDGSKSLSPEEFKKGVTDIGLDLTDSEIDEMFSRFDTDGSGNINMTEFLVKLRPP----MNNSRISIIEKAFDKM 127
Cdd:NF041410  33 FAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAPPPppppDQAPSTELADDLLSAL 112

                         90
                 ....*....|...
gi 24646398  128 DANGDGQITVTDL 140
Cdd:NF041410 113 DTDGDGSISSDEL 125

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398   48 LSRSFRVMDDDGSKSLSPEEFKKGVT------DIGLDLTDSeiDEMFSRFDTDGSGNINMTEFLVKLRPPMNNSRISIIe 121
Cdd:NF041410  65 LSELFSDLDSDGDGSLSSDELAAAAPppppppDQAPSTELA--DDLLSALDTDGDGSISSDELSAGLTSAGSSADSSQL- 141

                         90       100
                 ....*....|....*....|
gi 24646398  122 kaFDKMDANGDGQITVTDLK 141
Cdd:NF041410 142 --FSALDSDGDGSVSSDELA 159

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 24646398  45 ILGLSRSFRVMDDDGSKSLSPEEFKKGVTDIGLDLTDSEIDEMFSRFDTDGSGNINMTEFLvklrppmnnsRISI----I 120
Cdd:cd16185  65 LSNMQNGFEQRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFDPDRGGSLGFDDYI----------ELCIflasA 134

                        90
                ....*....|....*...
gi 24646398 121 EKAFDKMDANGDGQITVT 138
Cdd:cd16185 135 RNLFQAFDRQRTGRVTLD 152

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 24646398  19 RELANGLDKDPIYKLRLQCFSRGATGILGLSRSFRVMDDDGSKSLSPEEFKKGVTDIGLDLTDSEIDEMFSRFDtDGSGN 98
Cdd:cd15897  43 RSMIAMMDRDHSGKLNFSEFKGLWNYIKAWQEIFRTYDTDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYD-RGRGN 121

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 24646398  99 INMTEF---LVKLRPpmnnsrisiIEKAFDKMDANGDGQITVT 138
Cdd:cd15897 122 IDFDDFiqcCVRLQR---------LTDAFRRYDKDQDGQIQVN 155

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398   52 FRVMDDDGSKSLSPEEFKKGVTDIGlDLTDSEidEMFSRFDTDGSGNINMTEFLVKLRPP 111
Cdd:NF041410 109 LSALDTDGDGSISSDELSAGLTSAG-SSADSS--QLFSALDSDGDGSVSSDELAAALQPP 165

EF-hand, calcium binding motif, found in beta-parvalbumin; Beta-parvalbumin, also termed Oncomodulin-1 (OM), is a small calcium-binding protein that is expressed in hepatomas, as well as in the blastocyst and the cytotrophoblasts of the placenta. It is also found to be expressed in the cochlear outer hair cells of the organ of Corti and frequently expressed in neoplasms. Mammalian beta-parvalbumin is secreted by activated macrophages and neutrophils. It may function as a tissue-specific Ca2+-dependent regulatory protein, and may also serve as a specialized cytosolic Ca2+ buffer. Beta-parvalbumin acts as a potent growth-promoting signal between the innate immune system and neurons in vivo. It has high and specific affinity for its receptor on retinal ganglion cells (RGC) and functions as the principal mediator of optic nerve regeneration. It exerts its effects in a cyclic adenosine monophosphate (cAMP)-dependent manner and can further elevate intracellular cAMP levels. Moreover, beta-parvalbumin is associated with efferent function and outer hair cell electromotility, and can identify different hair cell types in the mammalian inner ear. Beta-parvalbumin is 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+. The EF site displays a high-affinity for Ca2+/Mg2+, and the CD site is a low-affinity Ca2+-specific site. In addition, beta-parvalbumin is distinguished from other parvalbumins by its unusually low isoelectric point (pI = 3.1) and sequence eccentricities (e.g., Y57-L58-D59 instead of F57-I58-E59).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24646398  52 FRVMDDDGSKSLSPEEFK---KGVTDIGLDLTDSEIDEMFSRFDTDGSGNINMTEF--LVK 107
Cdd:cd16255  40 FEIIDQDKSGFIEEEELKlflQNFSSGARELTDAETKAFLKAGDSDGDGKIGVEEFqaLVK 100

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 24646398  49 SRSFRVMDDDGSKSLSPEEFKKGVTDIGLDLTDSEIDEMFSRFDTDGSGNINMTEFLvklrppmnnsRISIIEK----AF 124
Cdd:cd16180  70 RRLFRRFDRDRSGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRRRGSISFDDFV----------EACVTLKrltdAF 139

                        90
                ....*....|....
gi 24646398 125 DKMDANGDGQITVT 138
Cdd:cd16180 140 RKYDTNRTGYATIS 153

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 24646398  50 RSFRVMDDDGSKSLSPEEFK---KGVTDIGLDLTDSEIDEMFSRFDTDGSGNINMTEF 104
Cdd:cd16251  38 KVFQILDKDKSGFIEEEELKyilKGFSIAGRDLTDEETKALLAAGDTDGDGKIGVEEF 95

EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also termed stromal cell-derived factor 4 (SDF-4), is a soluble, lumenal Golgi resident low-affinity Ca2+-binding protein that contains six copies of the EF-hand Ca2+-binding motif. It is required for secretory pathway calcium ATPase1 (SPCA1)-dependent Ca2+ import into the trans-Golgi network (TGN) and plays an essential role in Ca2+-dependent secretory cargo sorting at the TGN.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398  60 SKSLSPEEFKKGVTDIGLDLTDSEIDE-------MFSRFDTDGSGNINMTEFLVKLRPpmNNSRISIIEKAFD---KMDA 129
Cdd:cd16225 102 SKGYSEEEAEEKIKNNEELKLDEDDKEvldrykdRWSQADEPEDGLLDVEEFLSFRHP--EHSRGMLKNMVKEilhDLDQ 179

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24646398 130 NGDGQITVTDLKNVYSVRDHPKylsGEMTENQIFTQFLKNF-EVGAPNPDGIVTREEFINY 189
Cdd:cd16225 180 DGDEKLTLDEFVSLPPGTVEEQ---QAEDDDEWKKERKKEFeEVIDLNHDGKVTKEELEEY 237

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 24646398     83 EIDEMFSRFDTDGSGNINMTEFLVKLR 109
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLK 27

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 24646398  13 LKNLAKRELANG---LDKDPIYKLRLQCFSRgatgiLGLSRS---FRVMDDDGSKSLSPEEF-KKGVTDIGLDLTDSEID 85
Cdd:cd16227  38 LAVLAKKMDLNDdgfIDRKELKAWILRSFKM-----LDEEEAnerFEEADEDGDGKVTWEEYlADSFGYDDEDNEEMIKD 112

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24646398  86 -------------EMFSRFDTDGSGNINMTEFlVKLRPPMNNSRIS--IIEKAFDKMDANGDGQIT 136
Cdd:cd16227 113 steddlklleddkEMFEAADLNKDGKLDKTEF-SAFQHPEEYPHMHpvLIEQTLRDKDKDNDGFIS 177

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1, or phospholipase C-eta-1 (PLC-eta-1), or phospholipase C-like protein 3 (PLC-L3), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the zona incerta and in the spinal cord. PI-PLC-eta1 may perform a fundamental role in the brain. It may also act in synergy with other PLC subtypes. For instance, it is activated via intracellular Ca2+ mobilization and then plays a role in the amplification of GPCR (G-protein-coupled receptor)-mediated PLC-beta signals. In addition, its activity can be stimulated by ionomycin. PI-PLC-eta1 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398  48 LSRSFRVMDDDGSKSLSPEEFKKGVTDIGLDLTDSEIDEMFSRFDTD-GSGNINMTEFLVKLRPPMNNSRISIIEKAFdk 126
Cdd:cd16220   2 VKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDeNQGTLTFEEFCVFYKMMSLRRDLYLLLLSY-- 79

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24646398 127 mdangdgqitvTDLKNVYSVRDHPKYLSGEMTENQIFTQF----LKNFEVGAPNPD-GIVTREEFINY 189
Cdd:cd16220  80 -----------SDKKDHLTVEELAQFLKVEQKMNNVTTEYcldiIKKFEVSEENKEqNVLGIEGFTNF 136

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398 120 IEKAFDKMDANGDGQITVTDLKNVYsvRDHPKYLSGEMtenqiftqflknfevgAPNPDGIVTREEFINYYATISASI-- 197
Cdd:COG5126   7 LDRRFDLLDADGDGVLERDDFEALF--RRLWATLFSEA----------------DTDGDGRISREEFVAGMESLFEATve 68

                        90
                ....*....|
gi 24646398 198 -DNDAYFDLM 206
Cdd:COG5126  69 pFARAAFDLL 78

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 24646398  48 LSRSFRVMDDDGSKSLSPEEFKKGVTDIGLDLTDSEIDEMFSRFDTDGSGNINMTEFLV---KL--RPPmnnsrisiIEK 122
Cdd:cd16202   2 LKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVQfynRLtkRPE--------IEE 73

                        90       100
                ....*....|....*....|
gi 24646398 123 AFDKMDANGDgQITVTDLKN 142
Cdd:cd16202  74 LFKKYSGDDE-ALTVEELRR 92

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), calpain-B (CalpB), and similar proteins; The family contains two calpains that have been found in Drosophila, CalpA and CalpB. CalpA, also termed calcium-activated neutral proteinase A (CANP A), or calpain-A catalytic subunit, is a Drosophila calpain homolog specifically expressed in a few neurons in the central nervous system, in scattered endocrine cells in the midgut, and in blood cells. CalpB, also termed calcium-activated neutral proteinase B (CANP B), contains calpain-B catalytic subunit 1 and calpain-B catalytic subunit 2. Both CalpA and CalpB are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. Besides, CalpA and CalpB display some distinguishing structural features that are not found in mammalian typical calpains. CalpA harbors a 76 amino acid long hydrophobic stretch inserted in domain IV, which may be involved in membrane attachment of this enzyme. CalpB has an unusually long N-terminal tail of 224 amino acids, which belongs to the class of intrinsically unstructured proteins (IUP) and may become ordered upon binding to target protein(s). Moreover, they do not need small regulatory subunits for their catalytic activity, and their proteolytic function is not regulated by an intrinsic inhibitor as the Drosophila genome contains neither regulatory subunit nor calpastatin orthologs. As a result, they may exist as a monomer or perhaps as a homo- or heterodimer together with a second large subunit. Furthermore, both CalpA and CalpB are dispensable for viability and fertility and do not share vital functions during Drosophila development. Phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol, and phosphatidic acid can stimulate the activity and the rate of activation of CalpA, but not CalpB. Calpain A modulates Toll responses by limited Cactus/IkappaB proteolysis. CalpB directly interacts with talin, an important component of the focal adhesion complex, and functions as an important modulator in border cell migration within egg chambers, which may act via the digestion of talin. CalpB can be phosphorylated by cAMP-dependent protein kinase (protein kinase A, PKA; EC 2.7.11.11) at Ser240 and Ser845, as well as by mitogen-activated protein kinase (ERK1 and ERK2; EC 2.7.11.24) at Thr747. The activation of the ERK pathway by extracellular signals results in the phosphorylation and activation of calpain B. In Schneider cells (S2), calpain B was mainly in the cytoplasm and upon a rise in Ca2+ the enzyme adhered to intracellular membranes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646398  55 MDDDGSKSLSPEEFKKGVTDIGLDLTdseideMFSRFDTDGSGNINMTEflvkLRPPMNNSRISIIEKAFDKMD---ANG 131
Cdd:cd16196  50 MDVDRSGKLGFEEFKKLWEDLRSWKR------VFKLFDTDGSGSFSSFE----LRNALNSAGFRLSNATLNALVlrySNK 119

                ....*...
gi 24646398 132 DGQITVTD 139
Cdd:cd16196 120 DGRISFDD 127