EF-hand domain pair;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039758339 119 PSGIVNEENFKQIYSQFFPQGDSSNYATFLFNAFDTNHDGSVSFEDFVAGL 169
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLL 51

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039758339 180 RLNWAFNLYDLNKDGCITKEEMLDIMKSIYDMMgkytypalreeaPREHVESFFQKMDRNKDGVVTIEEFIE 251
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGL------------SEEEIDEMIREVDKDGDGKIDFEEFLE 60

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 1039758339  181 LNWAFNLYDLNKDGCITKEEMLDIMKSI 208
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

XopAW family type III secretion system calcium-binding effector;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039758339 138 QGDSSNYATFLFNAFDTNHDGSVSFEDFVAGLSVILRGTIDDRLNWAFNLYDLNKDGCITKEEMLDIMKSIydmmgkyty 217
Cdd:NF041410   22 SARSQQFQKQLFAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAPPP--------- 92

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039758339 218 PALREEAP-REHVESFFQKMDRNKDGVVTIEEFIESCQQDENIMRSMQLFD 267
Cdd:NF041410   93 PPPPDQAPsTELADDLLSALDTDGDGSISSDELSAGLTSAGSSADSSQLFS 143

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039758339 180 RLNWAFNLYDLNKDGCITKEEMLDIMKSIYDMMgkytypalreeaPREHVESFFQKMDRNKDGVVTIEEFIE 251
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGL------------SEEEIDEMIREVDKDGDGKIDFEEFLE 60

EF-hand domain pair;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039758339 178 DDRLNWAFNLYDLNKDGCITKEEMLDIMKSIydmmgkytypALREEAPREHVESFFQKMDRNKDGVVTIEEFIE 251
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKL----------EEGEPLSDEEVEELFKEFDLDKDGRISFEEFLE 64

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039758339 147 FLFNAFDTNHDGSVSFEDFVAGLSVILRG--TIDDRLNWAFNLYDLNKDGCITKEEMLDIMK 206
Cdd:pfam13499   6 EAFKLLDSDGDGYLDVEELKKLLRKLEEGepLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

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 1039758339  181 LNWAFNLYDLNKDGCITKEEMLDIMKSI 208
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039758339  148 LFNAFDTNHDGSVSFEDFVA-----GLSvilrgtiDDRLNWAFNLYDLNKDGCITKEEMLDIMKSIYDMMGKYTYPAlre 222
Cdd:smart00027  15 IFRSLDKNQDGTVTGAQAKPillksGLP-------QTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGYPIPA--- 84

                           90
                   ....*....|..
gi 1039758339  223 EAPREHVESFFQ 234
Cdd:smart00027  85 SLPPSLIPPSKR 96

centrin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039758339 184 AFNLYDLNKDGCITKEEMLDIMKSiydmmgkytypaLREEAPREHVESFFQKMDRNKDGVVTIEEFIESCQQ-------D 256
Cdd:PTZ00183   22 AFDLFDTDGSGTIDPKELKVAMRS------------LGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKklgerdpR 89

                          90
                  ....*....|.
gi 1039758339 257 ENIMRSMQLFD 267
Cdd:PTZ00183   90 EEILKAFRLFD 100

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 1039758339 149 FNAFDTNHDGSVSFEDFVAGLSVILRGTIDDRLNWA------------FNLYDLNKDGCITKEEMLDIMksiydmmgkyt 216
Cdd:cd16226    77 WKEYDPNKDGKLSWEEYKKATYGFLDDEEEDDDLHEsykkmirrderrWKAADQDGDGKLTKEEFTAFL----------- 145

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1039758339 217 YPalrEEAP--RE-HVESFFQKMDRNKDGVVTIEEFI 250
Cdd:cd16226   146 HP---EEFPhmRDiVVQETLEDIDKNKDGFISLEEYI 179

EF-hand domain pair;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039758339 119 PSGIVNEENFKQIYSQFFPQGDSSNYATFLFNAFDTNHDGSVSFEDFVAGL 169
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLL 51

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 1039758339 149 FNAFDTNHDGSVSFEDFVAGLSVILRGTIDDRLNWAFNLYDLNKDGCITKEEMLDIMKSiydmmgkytypaLREeapREH 228
Cdd:cd15898     6 WIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKS------------LTE---RPE 70

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1039758339 229 VESFFQKMDRNKDGVVTIEEFIESCQ--QDENI 259
Cdd:cd15898    71 LEPIFKKYAGTNRDYMTLEEFIRFLReeQGENV 103

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 1039758339 153 DTNHDGSVSFEDFVAGLsVILRGTIDDrLNW------AFNLY-DLNKDGCITKEEMLD-IMKSIYDmmgkytyPAlREEA 224
Cdd:cd16226   166 DKNKDGFISLEEYIGDM-YRDDDEEED-PDWvksereQFKEFrDKNKDGKMDREEVKDwILPEDYD-------HA-EAEA 235

                          90       100
                  ....*....|....*....|....*..
gi 1039758339 225 prEHVesfFQKMDRNKDGVVTIEEFIE 251
Cdd:cd16226   236 --KHL---IYEADDDKDGKLTKEEILD 257

EF-hand-like motif found in the dystrophin/dystrobrevin/dystrotelin family; The dystrophin/dystrobrevin/dystrotelin family has been characterized by a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. Dystrophin is the founder member of this family. It is a sub-membrane cytoskeletal protein associated with the inner surface membrane. Dystrophin and its close paralog utrophin have a large N-terminal extension of actin-binding CH domains, up to 24 spectrin repeats, and a WW domain. Its further paralog, dystrophin-related protein 2 (DRP-2), retains only two of the spectrin repeats. Dystrophin, utrophin or DRP2 can form the core of a membrane-bound complex consisting of dystroglycan, sarcoglycans and syntrophins, known as the dystrophin-glycoprotein complex (DGC) that plays an important role in brain development and disease, as well as in the prevention of muscle damage. Dystrobrevins, including alpha- and beta-dystrobrevin, lack the large N-terminal extension found in dystrophin, but alpha-dystrobrevin has a characteristic C-terminal extension. Dystrobrevins are part of the DGC. They physically associate with members of the dystrophin family and with the syntrophins through their homologous C-terminal coiled coil motifs. In contrast, dystrotelins lack both the large N-terminal extension found in dystrophin and the obvious syntrophin-binding sites (SBSs). Dystrotelins are not critical for mammalian development. They may be involved in other forms of cytokinesis. Moreover, dystrotelin is unable to heterodimerize with members of the dystrophin or dystrobrevin families, or to homodimerize.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1039758339 147 FLFNAFDTNHDGSVSFEDFVAGLSVILRGTIDDRLNWAFNLYDlNKDGCITKEEMLDIMKsiyDMM 212
Cdd:cd15901    58 WLLNLYDRNRTGCIRLLSVKIALITLCAASLLDKYRYLFGQLA-DSSGFISRERLTQFLQ---DLL 119

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039758339 180 RLNWAFNLYDLNKDGCITKEEMLDIMKSiydmmgkytypaLREEAPREHVESFFQKMDRNKDGVVTIEEFIE 251
Cdd:cd15898     1 WLRRQWIKADKDGDGKLSLKEIKKLLKR------------LNIRVSEKELKKLFKEVDTNGDGTLTFDEFEE 60

Secreted protein acidic and rich in cysteine Ca binding region; The SPARC_Ca_bdg domain of Secreted Protein Acidic and Rich in Cysteine is responsible for the anti-spreading activity of human urothelial cells. It is rich in alpha-helices. This extracellular calcium-binding domain contains two EF-hands that each coordinates one Ca2+ ion, forming a helix-loop-helix structure that not only drives the conformation of the protein but is also necessary for biological activity. The anti-spreading activity was dependent on the coordination of Ca2+ by a Glu residue at the Z position of EF-hand 2.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039758339 150 NAFDTNHDGSVSFEDFVAGLSVIlrgtiDDRLNWAFNLYDLNKDGCITKEEmLDIMKSIYDMMGKYTYPalreeaprehv 229
Cdd:pfam10591  29 RRERKDHSSTLEKRDESLLYPCC-----KDPLGWMFKRLDTNDDLLLDHEE-LAPIRAPLKPEEHCIKP----------- 91

                          90       100
                  ....*....|....*....|
gi 1039758339 230 esFFQKMDRNKDGVVTIEEF 249
Cdd:pfam10591  92 --FFESCDANKDKLISLEEW 109

EF-hand domain pair;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1039758339 120 SGIVNEENFKQIYSQFFPQGD-SSNYATFLFNAFDTNHDGSVSFEDFVAGLS 170
Cdd:pfam13499  16 DGYLDVEELKKLLRKLEEGEPlSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

centrin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039758339 148 LFNAFDTNHDGSVSFEDFVAGLSVILrGTIDDR--LNWAFNLYDLNKDGCITkeemLDIMKSIYDMMGKytypALREEAP 225
Cdd:PTZ00183   58 MIADVDKDGSGKIDFEEFLDIMTKKL-GERDPReeILKAFRLFDDDKTGKIS----LKNLKRVAKELGE----TITDEEL 128

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1039758339 226 REHVEsffqKMDRNKDGVVTIEEFIescqqdeNIMRSMQLF 266
Cdd:PTZ00183  129 QEMID----EADRNGDGEISEEEFY-------RIMKKTNLF 158

EF hand;

                          10        20
                  ....*....|....*....|.
gi 1039758339 229 VESFFQKMDRNKDGVVTIEEF 249
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEEL 21