EF-hand domain pair;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1720415285  37 PSGVVNEETFKEIYSQFFPQGDSTTYAHFLFNAFDTDHNGAVSFEDFI 84
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFC 48

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720415285  66 LFNAFDTDHNGAVSFEDFIKGLSILLRGTVQEKLNWAFNLYDINKDGYITKEEMLDIMKAI 126
Cdd:COG5126    38 LFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTAL 98

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 1720415285   98 KLNWAFNLYDINKDGYITKEEMLDIMKAI 126
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

calmodulin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720415285  44 ETFKEIYSQFFPQGDST-----------------TYAHF--LFNAFDTDHNGAVSFEDFIKGLSILLRGT-VQEKLNWAF 103
Cdd:PTZ00184   11 AEFKEAFSLFDKDGDGTittkelgtvmrslgqnpTEAELqdMINEVDADGNGTIDFPEFLTLMARKMKDTdSEEEIKEAF 90

                          90       100
                  ....*....|....*....|
gi 1720415285 104 NLYDINKDGYITKEEMLDIM 123
Cdd:PTZ00184   91 KVFDRDGNGFISAAELRHVM 110

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720415285  66 LFNAFDTDHNGAVSFEDFIKGLSILLRGTVQEKLNWAFNLYDINKDGYITKEEMLDIMKAI 126
Cdd:COG5126    38 LFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTAL 98

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720415285  61 TYAHFLFNAFDTDHNGAVSFEDFIKGLSILLRG--TVQEKLNWAFNLYDINKDGYITKEEMLDIMK 124
Cdd:pfam13499   2 EKLKEAFKLLDSDGDGYLDVEELKKLLRKLEEGepLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720415285   55 PQGDSTTYAHfLFNAFDTDHNGAVSFEDfikGLSILLR-GTVQEKLNWAFNLYDINKDGYITKEEMLDIMKAIYDMM 130
Cdd:smart00027   5 SPEDKAKYEQ-IFRSLDKNQDGTVTGAQ---AKPILLKsGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKL 77

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 1720415285  98 KLNWAFNLYDINKDGYITKEEMLDIMKAI 126
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29

EF-hand domain pair;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1720415285  37 PSGVVNEETFKEIYSQFFPQGDSTTYAHFLFNAFDTDHNGAVSFEDFI 84
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFC 48

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 1720415285  38 SGVVNEETFKEIYSQFFPQGdSTTYAHFLFNAFDTDHNGAVSFEDFIKGLSILlrgTVQEKLNWAFNLYDINKDGYITKE 117
Cdd:cd15898    14 DGKLSLKEIKKLLKRLNIRV-SEKELKKLFKEVDTNGDGTLTFDEFEELYKSL---TERPELEPIFKKYAGTNRDYMTLE 89

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1720415285 118 EMLDIMKAiydmmgkctypVLKEDAPRQHVETFFQ 152
Cdd:cd15898    90 EFIRFLRE-----------EQGENVSEEECEELIE 113

EF-hand domain pair;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720415285  97 EKLNWAFNLYDINKDGYITKEEMLDIMKAIYdmmgkctypvLKEDAPRQHVETFFQ 152
Cdd:pfam13499   2 EKLKEAFKLLDSDGDGYLDVEELKKLLRKLE----------EGEPLSDEEVEELFK 47

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720415285  65 FLFNAFDTDHNGAVSFEDFIKGLSILLRGTVQEKLNWAFNLYDiNKDGYITKE-------EMLDIMKAIY 127
Cdd:cd15901    58 WLLNLYDRNRTGCIRLLSVKIALITLCAASLLDKYRYLFGQLA-DSSGFISRErltqflqDLLQIPDLIG 126

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720415285  68 NAFDTDHNGAVSFEDFIKGLSIllrgtVQEKLNWAFNLYDINKDGYITKEEmLDIMKAIYDMMGKCTYPVLKED 141
Cdd:pfam10591  29 RRERKDHSSTLEKRDESLLYPC-----CKDPLGWMFKRLDTNDDLLLDHEE-LAPIRAPLKPEEHCIKPFFESC 96

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720415285  71 DTDHNGAVSFEDFIKglsiLLRGTV--QEKLNWAF-------NLYDINKDGYITKEEMLDIM 123
Cdd:cd15899   170 DKNGDGFISLEEFIS----DPYSADenEEEPEWVKvekerfvELRDKDKDGKLDGEELLSWV 227