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 1720415279 107 YAHFLFNAFDTDHNGAVSFEDFIKGLSILLRGTVQEKLNWAFNLYDINKDGYITKEEMLDIMK 169
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720415279 107 YAHFLFNAFDTDHNGAVSFEDFIKGLSILLRGTVQEKLNWAFNLYDINKDGYITKEEMLDIMK 169
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720415279 106 TYAHFLFNAFDTDHNGAVSFEDFIKGLSILLRG--TVQEKLNWAFNLYDINKDGYITKEEMLDIMK 169
Cdd:pfam13499   2 EKLKEAFKLLDSDGDGYLDVEELKKLLRKLEEGepLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

EF-hand domain pair;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1720415279  82 PSGVVNEETFKEIYSQFFPQGDSTTYAHFLFNAFDTDHNGAVSFEDFI 129
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFC 48

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 1720415279 107 YAHFLFNAFDTDHNGAVSFEDFIKGLSILLRGTVQEKLNWAFNLYDINKDGYITKEEMLDIMK 169
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720415279  83 SGVVNEETFKEIYSQFFPQGDSTTyAHFLFNAFDTDHNGAVSFEDFIKGLSILlrGTVQEKLNWAFNLYDINKDGYITKE 162
Cdd:COG5126    47 DGRISREEFVAGMESLFEATVEPF-ARAAFDLLDTDGDGKISADEFRRLLTAL--GVSEEEADELFARLDTDGDGKISFE 123

                          90
                  ....*....|
gi 1720415279 163 EMLDIMKAIY 172
Cdd:COG5126   124 EFVAAVRDYY 133

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 1720415279  143 KLNWAFNLYDINKDGYITKEEMLDIMKAI 171
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

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
                  ....*....|....*....|....*....|....*
gi 1720415279 143 KLNWAFNLYDINKDGYITKEEMLDIMKAIYDMMGK 177
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSE 35

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720415279 111 LFNAFDTDHNGAVSFEdfiKGLSILLR-GTVQEKLNWAFNLYDINKDGYITKEEMLDIMKAIYDMM 175
Cdd:cd00052     4 IFRSLDPDGDGLISGD---EARPFLGKsGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALAL 66

EF-hand domain pair;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1720415279  82 PSGVVNEETFKEIYSQFFPQGDSTTYAHFLFNAFDTDHNGAVSFEDFI 129
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFC 48

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1720415279 110 FLFNAFDTDHNGAVSFEDFIKGLSILLRgtvqekLNWAFNLYDINKDGYIT 160
Cdd:cd16180   107 LLVRKFDRRRRGSISFDDFVEACVTLKR------LTDAFRKYDTNRTGYAT 151

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 1720415279  70 LQILYRGFK--NECPSGVVN-EETFKEIYSQFFPQGDSTTYAhfLFNAFDTDHNGAVSFEDFIkGLSILLRGTvqeklNW 146
Cdd:cd16185    65 LSNMQNGFEqrDTSRSGRLDaNEVHEALAASGFQLDPPAFQA--LFRKFDPDRGGSLGFDDYI-ELCIFLASA-----RN 136

                          90
                  ....*....|....
gi 1720415279 147 AFNLYDINKDGYIT 160
Cdd:cd16185   137 LFQAFDRQRTGRVT 150

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 1720415279 110 FLFNAFDTDHNGAVSFEDFIKGLSILLRGTVQEKLNWAFNLYDiNKDGYITKE-------EMLDIMKAIY 172
Cdd:cd15901    58 WLLNLYDRNRTGCIRLLSVKIALITLCAASLLDKYRYLFGQLA-DSSGFISRErltqflqDLLQIPDLIG 126