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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33285021 115 KLRFAFQLYDLDRDGKISRNEMLQVLRLMvGVQVTDEQLESItdrtVQEADEDGDGAVSFLEFAK 179
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSL-GEGLSEEEIDEM----IREVDKDGDGKIDFEEFLE 60

calmodulin; Provisional

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 33285021  115 KLRFAFQLYDLDRDGKISRNEMLQVLRLMvGVQVTDEQLESItdrtVQEADEDGDGAVSFLEFAKSL 181
Cdd:PTZ00184  85 EIKEAFKVFDRDGNGFISAAELRHVMTNL-GEKLTDEEVDEM----IREADVDGDGQINYEEFVKMM 146

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 33285021 115 KLRFAFQLYDLDRDGKISRNEMLQVLRLMvGVQVTDEQLESItdrtVQEADEDGDGAVSFLEFAK 179
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSL-GEGLSEEEIDEM----IREVDKDGDGKIDFEEFLE 60

EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The family corresponds to a group of uncharacterized calglandulin-like proteins. Although their biological function remain unclear, they show high sequence similarity with human calglandulin-like protein GAGLP, which is an ortholog of calglandulin from the venom glands of Bothrops insularis snake. Both GAGLP and calglandulin are putative Ca2+-binding proteins with four EF-hand motifs. However, members in this family contain only three EF-hand motifs. In this point, they may belong to the parvalbumin-like EF-hand family, which is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33285021 116 LRFAFQLYDLDRDGKISRNEMLQVLRL----MVGVQVTDEQLESItdrtVQEADEDGDGAVSFLEFAKSLEK 183
Cdd:cd16252  39 IRKAFQMLDKDKSGFIEWNEIKYILSTvpssMPVAPLSDEEAEAM----IQAADTDGDGRIDFQEFSDMVKK 106

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33285021 115 KLRFAFQLYDLDRDGKISRNEMLQVLRLMvGVQVTDEQLESItdrtVQEADEDGDGAVSFLEFAK 179
Cdd:cd15898   1 WLRRQWIKADKDGDGKLSLKEIKKLLKRL-NIRVSEKELKKL----FKEVDTNGDGTLTFDEFEE 60

EF-hand domain;

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                  ....*....|....*....|....*....
gi 33285021   115 KLRFAFQLYDLDRDGKISRNEMLQVLRLM 143
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSL 29

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.

                          10        20
                  ....*....|....*....|....*....
gi 33285021   115 KLRFAFQLYDLDRDGKISRNEMLQVLRLM 143
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29

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 33285021    115 KLRFAFQLYDLDRDGKISRNEMLQVLRLM 143
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33285021 116 LRFAFQLYDLDRDGKISRNEMLQVLRLM--VGVQVTDEQLESItdrtVQEADEDGDGAVSFLEFAK 179
Cdd:cd16251  36 IKKVFQILDKDKSGFIEEEELKYILKGFsiAGRDLTDEETKAL----LAAGDTDGDGKIGVEEFAT 97

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33285021  85 RVLAYFRPIDEDDATLRDPKQPEPLNSRMNKLRFAFQLYDLDRDGKISRNEMLQVLRlmvgVQVTDEQLESITDRTVQEA 164
Cdd:cd15899  94 KNDTYGSVGDDEENVADNIKEDEEYKKLLLKDKKRFEAADQDGDLILTLEEFLAFLH----PEESPYMLDFVIKETLEDL 169

                        90
                ....*....|...
gi 33285021 165 DEDGDGAVSFLEF 177
Cdd:cd15899 170 DKNGDGFISLEEF 182