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
                ....*....|....*....|....*....|....*....|....*
gi 459668370 41 ELREAFRLYDKEGNGYIPTTCLREILRELDDQLTEHELDIMIEEI 85
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREV 45

EF-hand domain;

                         10        20        30
                 ....*....|....*....|....*....|
gi 459668370  41 ELREAFRLYDKEGNGYIPTTCLREILRELD 70
Cdd:pfam13405  1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30

centrin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459668370   2 LEELIDEVDEDKSGRLEFNEFVQLAAKFIVEEDAEamqKELREAFRLYDKEGNGYIPTTCLREILRELDDQLTEHELDIM 81
Cdd:PTZ00183  55 IKQMIADVDKDGSGKIDFEEFLDIMTKKLGERDPR---EEILKAFRLFDDDKTGKISLKNLKRVAKELGETITDEELQEM 131

                 ...
gi 459668370  82 IEE 84
Cdd:PTZ00183 132 IDE 134

Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family belongs to the second group of penta-EF hand (PEF) proteins. It includes classical (also called conventional or typical) calpain (referring to a calcium-dependent papain-like enzymes, EC 3.4.22.17) large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14) and two calpain small subunits (CAPNS1 and CAPNS2), which are largely confined to animals (metazoans). These PEF-containing are nonlysosomal intracellular calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates in response to calcium signalling. The classical mu- and m-calpains are heterodimers consisting of homologous but a distinct (large) L-subunit/chain (CAPN1 or CAPN2) and a common (small) S-subunit/chain (CAPNS1 or CAPNS2). These L-subunits (CAPN1 and CAPN2) and S-subunit CAPNS1 are ubiquitously found in all tissues. Other calpains likely consist of an isolated L-subunit/chain alone. Many of them, such as CAPNS2, CAPN3 (in skeletal muscle, or lens), CAPN8 (in stomach), CAPN9 (in digestive tracts), CAPN11 (in testis), CAPN12 (in follicles), are tissue-specific and have specific functions in distinct organs. The L-subunits of similar structure (called CALPA and B) also have been found in Drosophila melanogaster. The S-subunit seems to have a chaperone-like function for proper folding of the L-subunit. The catalytic L-subunits contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The S-subunits only have the PEF domain following an N-terminal Gly-rich hydrophobic domain. The calpains undergo a rearrangement of the protein backbone upon Ca2+-binding.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 459668370   5 LIDEVDEDKSGRLEFNEFVQLAAKFiveedaeamqKELREAFRLYDKEGNGYIPTTCLREILRELDDQL 73
Cdd:cd16182   47 LIALMDTNGSGRLDLEEFKTLWSDL----------KKWQAIFKKFDTDRSGTLSSYELRKALESAGFHL 105

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 459668370   5 LIDEVDEDKSGRLEFNEFVQLaAKFIveedaeamqKELREAFRLYDKEGNGYIPTTCLREILREL 69
Cdd:cd16180   42 MINMFDRDRSGTINFDEFVGL-WKYI---------QDWRRLFRRFDRDRSGSIDFNELQNALSSF 96

calmodulin; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 459668370  41 ELREAFRLYDKEGNGYIPTTCLREILRELDDQLTEHELDIMIEEI 85
Cdd:PTZ00184  12 EFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEV 56

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 459668370   3 EELIDEVDEDKSGRLEFNEFVQLAA-------KFIVEEDAEAMQKELREAFRLYDKEGNGYIPTTCLREILREL 69
Cdd:cd15902  137 KLILKEFDANKDGKLELDEMAKLLPvqenfllKFQILGAMDLTKEDFEKVFEHYDKDNNGVIEGNELDALLKDL 210

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
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 459668370  2 LEELIDEVDEDKSGRLEFNEFVQLAAKFIVEEDaeamQKELREAFRLYDKEGNGYI 57
Cdd:cd00051   2 LREAFRLFDKDGDGTISADELKAALKSLGEGLS----EEEIDEMIREVDKDGDGKI 53