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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13375787  66 DMIMDRVFRGFDKDNDGCVNVLEWIHGLSLFLRGSLEEKMKYCFEVFDLNGDGFISKEEMFHMLKNsllKQPSEEDPDEG 145
Cdd:COG5126  32 RRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTA---LGVSEEEADEL 108

                        90       100       110
                ....*....|....*....|....*....|.
gi 13375787 146 IkdlveitlKKMDHDHDGKLSFADYELAVRE 176
Cdd:COG5126 109 F--------ARLDTDGDGKISFEEFVAAVRD 131

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13375787  66 DMIMDRVFRGFDKDNDGCVNVLEWIHGLSLFLRGSLEEKMKYCFEVFDLNGDGFISKEEMFHMLKNsllKQPSEEDPDEG 145
Cdd:COG5126  32 RRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTA---LGVSEEEADEL 108

                        90       100       110
                ....*....|....*....|....*....|.
gi 13375787 146 IkdlveitlKKMDHDHDGKLSFADYELAVRE 176
Cdd:COG5126 109 F--------ARLDTDGDGKISFEEFVAAVRD 131

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 13375787  71 RVFRGFDKDNDGCVNVLEWIHGLSLFLRGSLEEKMKYCFEVFDLNGDGFISKEEMFHMLK 130
Cdd:cd00051   4 EAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

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 13375787    109 FEVFDLNGDGFISKEEMFHMLKN 131
Cdd:smart00054   6 FRLFDKDGDGKIDFEEFKDLLKA 28

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13375787  66 DMIMDRVFRGFDKDNDGCVNVLEWIHGLSLFLRGSLEEKMKYCFEVFDLNGDGFISKEEMFHMLKNsllKQPSEEDPDEG 145
Cdd:COG5126  32 RRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTA---LGVSEEEADEL 108

                        90       100       110
                ....*....|....*....|....*....|.
gi 13375787 146 IkdlveitlKKMDHDHDGKLSFADYELAVRE 176
Cdd:COG5126 109 F--------ARLDTDGDGKISFEEFVAAVRD 131

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 13375787  71 RVFRGFDKDNDGCVNVLEWIHGLSLFLRGSLEEKMKYCFEVFDLNGDGFISKEEMFHMLK 130
Cdd:cd00051   4 EAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

calmodulin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13375787   65 DDMIMDrvfrgFDKDNDGCVNVLEWIHGLSLFLRGS-LEEKMKYCFEVFDLNGDGFISKEEMFHMLKNsLLKQPSEEDPD 143
Cdd:PTZ00184  50 QDMINE-----VDADGNGTIDFPEFLTLMARKMKDTdSEEEIKEAFKVFDRDGNGFISAAELRHVMTN-LGEKLTDEEVD 123

                         90       100
                 ....*....|....*....|....*..
gi 13375787  144 EGIKDlveitlkkMDHDHDGKLSFADY 170
Cdd:PTZ00184 124 EMIRE--------ADVDGDGQINYEEF 142

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 13375787    71 RVFRGFDKDNDGCVNVLEWIHGLSLFLRGS--LEEKMKYCFEVFDLNGDGFISKEEMFHMLK 130
Cdd:pfam13499   6 EAFKLLDSDGDGYLDVEELKKLLRKLEEGEplSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand calcium-binding protein RLP49, 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 His-Asp-Glu-Leu (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 13375787  47 GLDRNAFRNILHVT-FGMTDDMIMDRVFRGFDKDNDGCVNVLEWIHGLSLFLRGSLE------EKMKYcFEVFDLNGDGF 119
Cdd:cd16230 139 MATREELTAFLHPEeFPHMRDIVVAETLEDLDKNKDGYVQVEEYIADLYSGEPGEEEpawvqtERQQF-RQFRDLNKDGR 217

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 13375787 120 ISKEEMFHMlknslLKQPSEEDPdegikdLVEIT--LKKMDHDHDGKLSFAD 169
Cdd:cd16230 218 LDGSEVGHW-----VLPPSQDQP------LVEANhlLHESDTDKDGRLSKAE 258

EF-hand, calcium binding motif, found in secretagogin (SCGN); 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 calcium sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. It also serves as a calcium buffer in neurons. Thus, SCGN may be linked to the pathogenesis of neurological diseases such as Alzheimer's, and also acts as a serum marker of neuronal damage, or as a tumor biomarker. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. All six EF hand motifs of SCGN in some eukaryotes, including D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, could potentially bind six calcium ions. In contrast, SCGNs from higher eukaryotes have at least one non-functional EF-hand motif due to the mutation(s) or deletions. For instance, the EF1 loop does not coordinate calcium ion due to the key residue asparagine replaced by lysine in SCGNs of many mammalian species. Moreover, the EF2 loop seems to be competent for calcium-binding in most mammalian SCGNs except for human and chimpanzee orthologs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13375787 112 FDLNGDGFISKEEMFHMLKNsLLKQPSEEDPDEGIKDLVEITLKKMDHDHDGKLSFADYE--LAVREETLLLEAFGPCLP 189
Cdd:cd16178 101 YDADSSGYISAAELKNFLRD-LFLQHKKVITEDKLDEYTDTMMKIFDKNKDGRLDLNDMAriLALQENFLLQFKMDAMSE 179

                        90
                ....*....|....
gi 13375787 190 DPKSQmEFEaQVFK 203
Cdd:cd16178 180 EERKR-DFE-KIFA 191

EF-hand domain;

                          10        20
                  ....*....|....*....|....*...
gi 13375787   104 KMKYCFEVFDLNGDGFISKEEMFHMLKN 131
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRS 28

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 13375787  76 FDKDNDGCVNVLEWIHGLSLFLRGSLEEKMKYCFEVFDlNGDGFISKEEMFHMLKNSL 133
Cdd:cd15901  63 YDRNRTGCIRLLSVKIALITLCAASLLDKYRYLFGQLA-DSSGFISRERLTQFLQDLL 119

EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and similar proteins; CBN, the product of the cbn gene, is a Drosophila homolog to vertebrate neuronal six EF-hand calcium binding proteins. It is expressed through most of ontogenesis with a selective distribution in the nervous system and in a few small adult thoracic muscles. Its precise biological role remains unclear. CBN contains six EF-hand motifs, but some of them may not bind calcium ions due to the lack of key residues.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 13375787 109 FEVFDLNGDGFISKEEMFHMLKNsLLKQPSEEDPDEGIKDLVEITLKKMDHDHDGKLS 166
Cdd:cd16179 194 FALYDRDNNGTIENEELTGFLKD-LLELVQEDYDEQDLEEFKEIILRGWDFNNDGKIS 250

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 13375787  72 VFRGFDKDNDGCVNVLE---WIHGLSL-FLRGSLEEKMKycfeVFDLNGDGFISKEEMFHMLKNSLLKQPSEEDPDEGIK 147
Cdd:cd16226  40 IVDKIDKNGDGFVTEEElkdWIKYVQKkYIREDVDRQWK----EYDPNKDGKLSWEEYKKATYGFLDDEEEDDDLHESYK 115

                        90       100
                ....*....|....*....|..
gi 13375787 148 DLVEITLKKM---DHDHDGKLS 166
Cdd:cd16226 116 KMIRRDERRWkaaDQDGDGKLT 137