EF-hand domain pair;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1003911033  74 PSGIVNEENFKQIYSQFFPQGDSSTYATFLFNAFDTDHDGSVSFEDFVSGL 124
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLL 51

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1003911033 135 RLNWAFNLYDLNKDGCITKEEMLDIMKSIYDMMgkytypamreeaPREHVENFFQKMDRNKDGVVTIEEFLE 206
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGL------------SEEEIDEMIREVDKDGDGKIDFEEFLE 60

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 1003911033  103 LFNAFDTDHDGSVSFED----FV-SGLSIILRGTIddrlnWafNLYDLNKDGCITKEEMLDIMKSIYDMMGKYTYPA 174
Cdd:smart00027  15 IFRSLDKNQDGTVTGAQakpiLLkSGLPQTLLAKI-----W--NLADIDNDGELDKDEFALAMHLIYRKLNGYPIPA 84

centrin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1003911033 139 AFNLYDLNKDGCITKEEMldimksiydmmgkytYPAMRE---EAPREHVENFFQKMDRNKDGVVTIEEFLESCQK----- 210
Cdd:PTZ00183   22 AFDLFDTDGSGTIDPKEL---------------KVAMRSlgfEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKklger 86

                          90
                  ....*....|....
gi 1003911033 211 --DENIMRSMQLFD 222
Cdd:PTZ00183   87 dpREEILKAFRLFD 100

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1003911033 135 RLNWAFNLYDLNKDGCITKEEMLDIMKSIYDMMgkytypamreeaPREHVENFFQKMDRNKDGVVTIEEFLE 206
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGL------------SEEEIDEMIREVDKDGDGKIDFEEFLE 60

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1003911033  75 SGIVNEENFKQIYSQFFPQGDSSTYATfLFNAFDTDHDGSVSFEDFVSGLSIIlrGTIDDRLNWAFNLYDLNKDGCITKE 154
Cdd:COG5126    47 DGRISREEFVAGMESLFEATVEPFARA-AFDLLDTDGDGKISADEFRRLLTAL--GVSEEEADELFARLDTDGDGKISFE 123

                          90
                  ....*....|
gi 1003911033 155 EMLDIMKSIY 164
Cdd:COG5126   124 EFVAAVRDYY 133

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1003911033 102 FLFNAFDTDHDGSVSFEDFVSGLSIILRG--TIDDRLNWAFNLYDLNKDGCITKEEMLDIMK 161
Cdd:pfam13499   6 EAFKLLDSDGDGYLDVEELKKLLRKLEEGepLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1003911033 107 FDTDHDGSVSFEDFVSGL----SIILRGTIDDRLNwafNLYDLNKDGCITKEEMLdimksiydmmgKYTYPAMrEEAPRE 182
Cdd:cd16227   168 KDKDNDGFISFQEFLGDRagheDKEWLLVEKDRFD---EDYDKDGDGKLDGEEIL-----------SWLVPDN-EEIAEE 232

                          90       100
                  ....*....|....*....|....
gi 1003911033 183 HVENFFQKMDRNKDGVVTIEEFLE 206
Cdd:cd16227   233 EVDHLFASADDDHDDRLSFDEILD 256

centrin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1003911033 139 AFNLYDLNKDGCITKEEMldimksiydmmgkytYPAMRE---EAPREHVENFFQKMDRNKDGVVTIEEFLESCQK----- 210
Cdd:PTZ00183   22 AFDLFDTDGSGTIDPKEL---------------KVAMRSlgfEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKklger 86

                          90
                  ....*....|....
gi 1003911033 211 --DENIMRSMQLFD 222
Cdd:PTZ00183   87 dpREEILKAFRLFD 100

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 1003911033  136 LNWAFNLYDLNKDGCITKEEMLDIMKSI 163
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1003911033 104 FNAFDTDHDGSVSFEDFV---------SGLSIILRGTIDDRLNWA-----FNLYDLNKDGCITKEEMLdimksiydmmgK 169
Cdd:cd16227    78 FEEADEDGDGKVTWEEYLadsfgyddeDNEEMIKDSTEDDLKLLEddkemFEAADLNKDGKLDKTEFS-----------A 146

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1003911033 170 YTYPamrEEAPREH---VENFFQKMDRNKDGVVTIEEFL 205
Cdd:cd16227   147 FQHP---EEYPHMHpvlIEQTLRDKDKDNDGFISFQEFL 182

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 1003911033 104 FNAFDTDHDGSVSFEDFVSGLSIILRGTIDDRLNWA------------FNLYDLNKDGCITKEEMLDIMKSiydmmgkYT 171
Cdd:cd16226    77 WKEYDPNKDGKLSWEEYKKATYGFLDDEEEDDDLHEsykkmirrderrWKAADQDGDGKLTKEEFTAFLHP-------EE 149

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1003911033 172 YPAMREEAPREHVEnffqKMDRNKDGVVTIEEFL 205
Cdd:cd16226   150 FPHMRDIVVQETLE----DIDKNKDGFISLEEYI 179

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 1003911033 108 DTDHDGSVSFEDFVSGLsIILRGTIDDrLNW------AFNLY-DLNKDGCITKEEMLD-IMKSIYDmmgkytyPAMrEEA 179
Cdd:cd16226   166 DKNKDGFISLEEYIGDM-YRDDDEEED-PDWvksereQFKEFrDKNKDGKMDREEVKDwILPEDYD-------HAE-AEA 235

                          90       100
                  ....*....|....*....|....*..
gi 1003911033 180 prEHVenfFQKMDRNKDGVVTIEEFLE 206
Cdd:cd16226   236 --KHL---IYEADDDKDGKLTKEEILD 257

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 1003911033 135 RLNWAFNLYDLNKDGCITKEEMLDIMKSI 163
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1003911033 133 DDRLNWAFNLYDLNKDGCITKEEMLDIMKSIYDMMgkytypamreeaprehvenfFQKMDRNKDGVVTIEEFLE 206
Cdd:COG5126     4 RRKLDRRFDLLDADGDGVLERDDFEALFRRLWATL--------------------FSEADTDGDGRISREEFVA 57

EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also termed stromal cell-derived factor 4 (SDF-4), is a soluble, lumenal Golgi resident low-affinity Ca2+-binding protein that contains six copies of the EF-hand Ca2+-binding motif. It is required for secretory pathway calcium ATPase1 (SPCA1)-dependent Ca2+ import into the trans-Golgi network (TGN) and plays an essential role in Ca2+-dependent secretory cargo sorting at the TGN.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1003911033 140 FNLYDLNKDGCITKEEMLD-IMKSIYDMMgkytypamrEEAPREHvENFFQKMDRNKDGVVTIEEF 204
Cdd:cd16225    40 FKKVDVNTDGFLSAEELEDwIMEKTQEHF---------QEAVEEN-EQIFKAVDTDKDGNVSWEEY 95

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1003911033 102 FLFNAFDTDHDGSVSFEDFVSGLSIILRGTIDDRLNWAFNLYDlNKDGCITKEEML----DIMKsIYDMMGKYTYPAMRE 177
Cdd:cd15901    58 WLLNLYDRNRTGCIRLLSVKIALITLCAASLLDKYRYLFGQLA-DSSGFISRERLTqflqDLLQ-IPDLIGESPAFGGHN 135

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1003911033 178 EAPRehVENFFQkMDRNKDGvVTIEEFLESCQ 209
Cdd:cd15901   136 VEAA--VESCFQ-LARSRVG-VSEDTFLSWLL 163