calmodulin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444727739  53 DMRHHGSFNYVKFFEHMKKFQGSGQLESVIRKAFQTLDKDKSGFIEWNEIKYILCTVpiagpTAPLTDEEAEAMIQAADT 132
Cdd:PTZ00184  57 DADGNGTIDFPEFLTLMARKMKDTDSEEEIKEAFKVFDRDGNGFISAAELRHVMTNL-----GEKLTDEEVDEMIREADV 131

                 ....*....
gi 444727739 133 DGDGRIDYE 141
Cdd:PTZ00184 132 DGDGQINYE 140

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 444727739  78 LESVIRKAFQTLDKDKSGFIEWNEIKYILCTVPiagptapLTDEEAEAMIQAADTDGDGRIDYE 141
Cdd:COG5126   67 VEPFARAAFDLLDTDGDGKISADEFRRLLTALG-------VSEEEADELFARLDTDGDGKISFE 123

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444727739  44 DKDIELLPADMRHHGSFNYVKFFEHMKKFQGSgqlESVIRKAFQTLDKDKSGFIEWNEIKYILCTVPIAGPTapLTDEEA 123
Cdd:cd16251    1 AKDIEKAPSAFRAHGSFNYKKFFEHVGLKQKS---EDQIKKVFQILDKDKSGFIEEEELKYILKGFSIAGRD--LTDEET 75

                         90       100
                 ....*....|....*....|....*.
gi 444727739 124 EAMIQAADTDGDGRIDYEALATPCQG 149
Cdd:cd16251   76 KALLAAGDTDGDGKIGVEEFATLVAG 101

EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2+/Mg2+-binding protein expressed mainly in fast-twitch skeletal myofibrils, where it may act as a soluble relaxing factor facilitating the Ca2+-mediated relaxation phase. It is also expressed in rapidly firing neurons, particularly GABA-ergic neurons, and thus may confer protection against Ca2+ toxicity. The major role of alpha-parvalbumin is metal buffering and transport of Ca2+. It binds different metal cations, and exhibits very high affinity for Ca2+ and physiologically significant affinity for Mg2+. Alpha-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+. Both metal ion-binding sites in alpha-parvalbumin are high-affinity sites. Additionally, in contrast to beta-parvalbumin, alpha-parvalbumin is less acidic and has an additional residue in the C-terminal helix.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444727739  44 DKDIELLPADMRHHGSFNYVKFFEhMKKFQGSGQLEsvIRKAFQTLDKDKSGFIEWNEIKYILCTVPIAGptAPLTDEEA 123
Cdd:cd16254    1 AEDIKKAVGAFAAADSFDYKKFFE-MVGLKKKSADD--VKKVFHILDKDKSGFIEEDELKFVLKGFSPDG--RDLSDKET 75

                         90       100
                 ....*....|....*....|..
gi 444727739 124 EAMIQAADTDGDGRIDYEALAT 145
Cdd:cd16254   76 KALLAAGDKDGDGKIGIDEFAT 97

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 444727739  82 IRKAFQTLDKDKSGFIEWNEIKYILctvPIAGPtaPLTDEEAEAMIQAADTDGDGRIDYE 141
Cdd:cd00051    2 LREAFRLFDKDGDGTISADELKAAL---KSLGE--GLSEEEIDEMIREVDKDGDGKIDFE 56

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444727739  44 DKDIELLPADMRHHGSFNYVKFFehmKKFQGSGQLESVIRKAFQTLDKDKSGFIEWNEIKYIL-CTVPIAgptAPLTDEE 122
Cdd:cd16253    1 ANDIDIALAACQAADSFDHKAFF---KAVGLSKKSPADIKKVFNILDQDKSGFIEEEELKLFLkNFSDGA---RVLSDKE 74

                         90       100
                 ....*....|....*....|...
gi 444727739 123 AEAMIQAADTDGDGRIDYEALAT 145
Cdd:cd16253   75 TKNFLAAGDSDGDGKIGVDEFKS 97

centrin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444727739  26 EFSSQMKkmalALGTSLSDKDIELLPADMRHHGS--FNYVKFFEHMKKFQGSGQLESVIRKAFQTLDKDKSGFIEWNEIK 103
Cdd:PTZ00183  38 ELKVAMR----SLGFEPKKEEIKQMIADVDKDGSgkIDFEEFLDIMTKKLGERDPREEILKAFRLFDDDKTGKISLKNLK 113

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 444727739 104 YILCTVpiaGPTapLTDEEAEAMIQAADTDGDGRIDYE 141
Cdd:PTZ00183 114 RVAKEL---GET--ITDEELQEMIDEADRNGDGEISEE 146

EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand calcium-binding protein RLP49, is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal His-Asp-Glu-Leu (HDEL) tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444727739  66 FEHMKKFqgsgqlesVIRKAFQTLDKDKSGFIEWNEIKYILCTVPIAGPTAPLTDEEAEAMIQAADTDGDGRIDYEALat 145
Cdd:cd16230  154 FPHMRDI--------VVAETLEDLDKNKDGYVQVEEYIADLYSGEPGEEEPAWVQTERQQFRQFRDLNKDGRLDGSEV-- 223

                         90
                 ....*....|
gi 444727739 146 pcqGVYLHPP 155
Cdd:cd16230  224 ---GHWVLPP 230

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444727739  70 KKFQGSGQLE---SVIRKAFQTLDKDKSGFIEWNEIKYI---LCTVPIAGPTAPLTDEEAEAMIQAADTDGDGRIDYEAL 143
Cdd:cd15902  168 LKFQILGAMDltkEDFEKVFEHYDKDNNGVIEGNELDALlkdLLEKNKADIDKPDLENFRDAILRACDKNKDGKIQKTEL 247

                 .
gi 444727739 144 A 144
Cdd:cd15902  248 A 248

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444727739  82 IRKAFQTLDKDKSGFIEWNEIKYI-------LCTVPIAGPTAPLTDEE----------------AEAMIQAADTDGDGRI 138
Cdd:COG5126    7 LDRRFDLLDADGDGVLERDDFEALfrrlwatLFSEADTDGDGRISREEfvagmeslfeatvepfARAAFDLLDTDGDGKI 86

                 ....*..
gi 444727739 139 DYEALAT 145
Cdd:COG5126   87 SADEFRR 93

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 444727739  82 IRKAFQTLDKDKSGFIEWNEIKYILCTVPIagptaPLTDEEAEAMIQAADTDGDGRIDYE 141
Cdd:cd16202    2 LKDQFRKADKNGDGKLSFKECKKLLKKLNV-----KVDKDYAKKLFQEADTSGEDVLDEE 56

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 444727739  86 FQTLDKDKSGFIEWNEIKYILctvpIAGPTAPLTDEEAEAMIQAADTDGDGRIDYE 141
Cdd:cd16183    6 FQRVDKDRSGQISATELQQAL----SNGTWTPFNPETVRLMIGMFDRDNSGTINFQ 57

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444727739  67 EHMKKFQGSGQLESViRKAFQTLDKDKSGFIEWNEIKYILCTVPIAGPTAPLTDEEAEAMIQ-------AADTDGDGRID 139
Cdd:cd16226   59 DWIKYVQKKYIREDV-DRQWKEYDPNKDGKLSWEEYKKATYGFLDDEEEDDDLHESYKKMIRrderrwkAADQDGDGKLT 137

                         90
                 ....*....|....*
gi 444727739 140 YEALATpcqgvYLHP 154
Cdd:cd16226  138 KEEFTA-----FLHP 147

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 444727739  82 IRKAFQTLDKDkSGFIEWNEIKYILCTVPIAGPTAPLTDEEAEAMIQAADTDGDGRIDYEA 142
Cdd:cd15897    2 LRNVFQAVAGD-DGEISATELQQALSNVGWTHFDLGFSLETCRSMIAMMDRDHSGKLNFSE 61

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 444727739  86 FQTLDKDKSGFIEWNE----IKYILCTVPIAGPTAPLTDEEAEAMIQAADTDGDGRIDYEALA 144
Cdd:cd15902    5 WMHFDADGNGYIEGKEldsfLRELLKALNGKDKTDDEVAEKKKEFMEKYDENEDGKIEIRELA 67