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 442616816   39 PNGLLTEQGFIKIYKQFFPQGDPSKFASLVFRVFDENNDGSIEFEEFIRAL 89
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 442616816 100 KLQWAFRLYDVDNDGYITREEMYNIVDAIYqmvgqqpqsedENTPQKRVDKIFDQMDKNHDGKLTLEEFREG 171
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSLG-----------EGLSEEEIDEMIREVDKDGDGKIDFEEFLEL 61

transaldolase;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 442616816 105 FRLYDVDNDGYITREEmynivdaiyqMVGQqpqsedentpqkrvDKIFDQMDKNHDGKLTLEEFREG 171
Cdd:PRK12309 340 FRLYDLDGDGFITREE----------WLGS--------------DAVFDALDLNHDGKITPEEMRAG 382

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 442616816   100 KLQWAFRLYDVDNDGYITREEMYNIVDAI 128
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        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 442616816  40 NGLLTEQGFIKIYKQFFPqGDPSKFASLVFRVFDENNDGSIEFEEFIRALS 90
Cdd:cd00051   14 DGTISADELKAALKSLGE-GLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 442616816 100 KLQWAFRLYDVDNDGYITREEMYNIVDAIYqmvgqqpqsedENTPQKRVDKIFDQMDKNHDGKLTLEEFREG 171
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSLG-----------EGLSEEEIDEMIREVDKDGDGKIDFEEFLEL 61

EF-hand domain pair;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 442616816   98 DEKLQWAFRLYDVDNDGYITREEMyniVDAIYQMVGQQPQSEDEntpqkrVDKIFDQMDKNHDGKLTLEEFRE 170
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEEL---KKLLRKLEEGEPLSDEE------VEELFKEFDLDKDGRISFEEFLE 64

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  28 RQWHKGFLKDCPN--GLLTEQGFIKIYKQFFPQGDPsKFASLVFRVFDENNDGSIEFEEFIRALSV--TSKGNLDEklqw 103
Cdd:COG5126   33 RLWATLFSEADTDgdGRISREEFVAGMESLFEATVE-PFARAAFDLLDTDGDGKISADEFRRLLTAlgVSEEEADE---- 107

                         90       100
                 ....*....|....*....|....*..
gi 442616816 104 AFRLYDVDNDGYITREEMYNIVDAIYQ 130
Cdd:COG5126  108 LFARLDTDGDGKISFEEFVAAVRDYYT 134

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  64 FASLVFRVFDENNDGSIEFEEFIRALSVTS--------KGN---LDEKLQWAFRLYDVDNDGYITREEMYNIVDAIYQMV 132
Cdd:cd16179  142 YTDTILQLFDRNKDGKLQLSEMARLLPVKEnflcrpifKGAgklTREDIDRVFALYDRDNNGTIENEELTGFLKDLLELV 221

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 442616816 133 GQQPQSEDENTPQKrvdKIFDQMDKNHDGKLTLEEFR 169
Cdd:cd16179  222 QEDYDEQDLEEFKE---IILRGWDFNNDGKISRKELT 255

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  63 KFASLVFRVFDENNDGSIEFEEFIRALSVTSKGNLDEKLQWAFRLYDVDNDGYITREEMynivdaiYQMVGQQPQSEDEN 142
Cdd:NF041410  27 QFQKQLFAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELFSDLDSDGDGSLSSDEL-------AAAAPPPPPPPDQA 99

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 442616816 143 TPQKRVDKIFDQMDKNHDGKLTLEEF-----REGSKAD 175
Cdd:NF041410 100 PSTELADDLLSALDTDGDGSISSDELsagltSAGSSAD 137

calmodulin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  73 DENNDGSIEFEEFIRALSVTSK-GNLDEKLQWAFRLYDVDNDGYITREEMYNIVDAIyqmvGQQPQSEDentpqkrVDKI 151
Cdd:PTZ00184  57 DADGNGTIDFPEFLTLMARKMKdTDSEEEIKEAFKVFDRDGNGFISAAELRHVMTNL----GEKLTDEE-------VDEM 125

                         90
                 ....*....|....*..
gi 442616816 152 FDQMDKNHDGKLTLEEF 168
Cdd:PTZ00184 126 IREADVDGDGQINYEEF 142

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 442616816 105 FRLYDVDNDGYITREEMYNIVDAIyqmvgqqpqsedeNTPQKRVDKIFDQMDKNHDGKLTLEEF 168
Cdd:cd00052    5 FRSLDPDGDGLISGDEARPFLGKS-------------GLPRSVLAQIWDLADTDKDGKLDKEEF 55

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 442616816  40 NGLLTEQGFIKIYKQFFPQGDPSKFASLvFRVFDENNDGSIEFEEFIRALSvtSKGNLDEkLQWAFRLYDVDNDGYITRE 119
Cdd:cd15898   14 DGKLSLKEIKKLLKRLNIRVSEKELKKL-FKEVDTNGDGTLTFDEFEELYK--SLTERPE-LEPIFKKYAGTNRDYMTLE 89

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 442616816 120 EMYNIvdaiyqMVGQQPQSEDEntpqKRVDKIFDQMDKN-HDGKLTLEEF 168
Cdd:cd15898   90 EFIRF------LREEQGENVSE----EECEELIEKYEPErENRQLSFEGF 129

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  59 GDPSKFA----SLVFRVFDENNDGSIEFEEFIralsvtskgNLDEKLQ-W--AFRLYDVDNDGYITREEM--------YN 123
Cdd:cd16180   29 GDWTPFSietvRLMINMFDRDRSGTINFDEFV---------GLWKYIQdWrrLFRRFDRDRSGSIDFNELqnalssfgYR 99

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 442616816 124 IVDAIYQMVGQQpqsEDENTPQ--------------KRVDKIFDQMDKNHDGKLTL--EEF 168
Cdd:cd16180  100 LSPQFVQLLVRK---FDRRRRGsisfddfveacvtlKRLTDAFRKYDTNRTGYATIsyEDF 157

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 442616816  68 VFRVFDENNDGSIEFEEF---IRALSVTSKgnlDEKLQWAFRLYDVDNDGYITREEMYNIVDAIyqmvgqqpqsedenTP 144
Cdd:cd15898    5 QWIKADKDGDGKLSLKEIkklLKRLNIRVS---EKELKKLFKEVDTNGDGTLTFDEFEELYKSL--------------TE 67

                         90       100
                 ....*....|....*....|....*.
gi 442616816 145 QKRVDKIFDQMDKNHDGKLTLEEFRE 170
Cdd:cd15898   68 RPELEPIFKKYAGTNRDYMTLEEFIR 93

EF-hand domain pair;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 442616816   77 DGSIEFEEFIRALSVTSKGNL-DEKLQWAFRLYDVDNDGYITREE 120
Cdd:pfam13833   2 KGVITREELKRALALLGLKDLsEDEVDILFREFDTDGDGYISFDE 46

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  69 FRVFDENNDGSIEFEEFIRALSVT-SKGNLDEKLQWAFRLYDVDNDGYITREEMynivdaIYQMVGQQPQSEDENTPQKR 147
Cdd:cd15899  129 FEAADQDGDLILTLEEFLAFLHPEeSPYMLDFVIKETLEDLDKNGDGFISLEEF------ISDPYSADENEEEPEWVKVE 202

                         90       100
                 ....*....|....*....|
gi 442616816 148 VDKIFDQMDKNHDGKLTLEE 167
Cdd:cd15899  203 KERFVELRDKDKDGKLDGEE 222

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  72 FDENNDGSIEFEE----------FIRALSVTSKGNLDEKLQWAFRLYDVDNDGYITREEMYNIvdaIYQMVGQQPQSEDE 141
Cdd:cd15902   53 YDENEDGKIEIRElanilpteenFLLLFRREQPLISSVEFMKIWRKYDTDGSGFIEAKELKGF---LKDLLLKNKKHVSP 129

                         90       100
                 ....*....|....*....|....*..
gi 442616816 142 NTPQKRVDKIFDQMDKNHDGKLTLEEF 168
Cdd:cd15902  130 PKLDEYTKLILKEFDANKDGKLELDEM 156

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  42 LLTEQGFIKIYKQFFPQGDPSKFASlVFRVFDENNDGSIEFEEFIR----ALSVTSKGNLDEKL----QWAFRLYDVDND 113
Cdd:cd15902   70 LPTEENFLLLFRREQPLISSVEFMK-IWRKYDTDGSGFIEAKELKGflkdLLLKNKKHVSPPKLdeytKLILKEFDANKD 148

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 442616816 114 GYITREEMYNIVDAIYQMVGQQPQSEDENTPQKRVDKIFDQMDKNHDGKLTLEE 167
Cdd:cd15902  149 GKLELDEMAKLLPVQENFLLKFQILGAMDLTKEDFEKVFEHYDKDNNGVIEGNE 202

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 442616816 100 KLQWAFRLYDVDNDGYITREEMYNIVDAIyqmvgqqpqseDENTPQKRVDKIFDQMDKNHDGKLTLEEFRE 170
Cdd:cd15898    1 WLRRQWIKADKDGDGKLSLKEIKKLLKRL-----------NIRVSEKELKKLFKEVDTNGDGTLTFDEFEE 60

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 442616816   100 KLQWAFRLYDVDNDGYITREEMYNIVDAI 128
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

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 442616816  66 SLVFRVFDENNDGSIEFEEFIRALSVTSKGNLDEKLQWAFRLYDvDNDGYITRE-------EMYNIVDAIY 129
Cdd:cd15901   57 NWLLNLYDRNRTGCIRLLSVKIALITLCAASLLDKYRYLFGQLA-DSSGFISRErltqflqDLLQIPDLIG 126

EF-hand domain;

                          10        20
                  ....*....|....*....|....*....
gi 442616816  100 KLQWAFRLYDVDNDGYITREEMYNIVDAI 128
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSL 29

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  57 PQGDPSKFASLVFRVFDENNDGSIEFEEFIRALSVTSK----GNLDEKLQWA------FRLYDVDNDGYITREEMYNIVD 126
Cdd:cd16179   43 SETALEELKEEFMEAYDENQDGRIDIRELAQLLPTEENflllFRRDNPLDSSvefmkvWREYDKDNSGYIEADELKNFLK 122

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 442616816 127 AIYQMVGQQPQSEDENTPQkRVDKIFDQMDKNHDGKLTLEE 167
Cdd:cd16179  123 HLLKEAKRDNDVSEDKLIE-YTDTILQLFDRNKDGKLQLSE 162

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 442616816  69 FRVFDENNDGSIEFEEFI-RALSVTSKGNLDEKLQWA-------------FRLYDVDNDGYITREEMYNIvdaiyqmvgQ 134
Cdd:cd16227   78 FEEADEDGDGKVTWEEYLaDSFGYDDEDNEEMIKDSTeddlklleddkemFEAADLNKDGKLDKTEFSAF---------Q 148

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 442616816 135 QPqsedENTPQKR---VDKIFDQMDKNHDGKLTLEEF 168
Cdd:cd16227  149 HP----EEYPHMHpvlIEQTLRDKDKDNDGFISFQEF 181

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 442616816  98 DEKLQWAFRLYDVDNDGYITREEM-YNIVDaiyQMVGQQPQSEDENtpqkrvDKIFDQMDKNHDGKLTLEEFR 169
Cdd:cd16225   33 RKKLKEIFKKVDVNTDGFLSAEELeDWIME---KTQEHFQEAVEEN------EQIFKAVDTDKDGNVSWEEYR 96

EF-hand, calcium binding motif, found in calumenin; Calumenin, also termed crocalbin, or IEF SSP 9302, 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 is highly expressed in various brain regions. Thus it plays an important role in migration and differentiation of neurons, and/or in Ca2+ signaling between glial cells and neurons. Calumenin is involved in Ca2+ homeostasis through interacting with ryanodine receptor RyR2 and SERCA2. It acts as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. Calumenin also forms a Ca2+-dependent complex with thrombospondin-1, which is broadly involved in haemostasis and thrombosis. Moreover, calumenin is a molecular chaperone that endogenously regulates the vitamin K-dependent gamma-carboxylation of several proteins, including blood coagulation factors (such as FII, FVII, FIX, FX, and proteins C, S and Z), cell survival factors (Gas6) and bone metabolism proteins (such as matrix Gla protein or MGP, osteocalcin and periostin), through targeting the gamma-glutamyl carboxylase. It also functions as a charged F508del-cystic fibrosis transmembrane regulator (CFTR) folding modulator, as well as a G551D-CFTR associated protein. Furthermore, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. It binds to and stabilizes fibulin-1, and further inactivates extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  50 KIYKQFFPQGDPSKFASLVFRVfDENNDGSIEFEEFIRALSVTSKGNLDEKLQWAFRLYDVDNDGYITREEMYNivdAIY 129
Cdd:cd16228   23 KTFDQLTPEESKERLGKIVGKI-DEDKDGFVTEDELKAWIKFAQKRWIYEDVERQWKGHDLNEDGLVSWEEYKN---ATY 98

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 442616816 130 QMVGQQPQSEDE-NTPQK--RVDKIFDQMDKNHDGKLTLEEF 168
Cdd:cd16228   99 GYILDDPDPDDGfNYKQMmvRDERRFKMADKDGDLRATKEEF 140

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 442616816   68 VFRVFDENNDGSIEFEEFIRALS 90
Cdd:pfam00036   5 IFRLFDKDGDGKIDFEEFKELLK 27

EF-hand, calcium binding motif, found in reticulocalbin-1 (RCN-1); RCN-1 is an endoplasmic reticulum resident low-affinity Ca2+-binding protein with six EF-hand motifs and a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It is expressed at the cell surface. RCN-1 acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signaling cascade. It also plays a key role in the development of doxorubicin-associated resistance.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  50 KIYKQFFPQGDPSKFASLVFRVfDENNDGSIEFEEFIRALSVTSKGNLDEKLQWAFRLYDVDNDGYITREEMYNivdAIY 129
Cdd:cd16229   23 KTFDQLTPEESKERLGKIVDRI-DDDKDGFVTTEELKAWIKRVQKRYIYENVAKVWKDYDLNKDNKISWEEYKQ---ATY 98

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 442616816 130 QMVGQQPQSEDENTPQ-------KRVDKIFDQMDKNHDGKLTLEEF 168
Cdd:cd16229   99 GYYLGNPEEFQDATDQfsfkkmlPRDERRFKAADLDGDLAATREEF 144

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 442616816 105 FRLYDVDNDGYITREEMYNIVDAIYQmvGQQPQSEDENTPQKRVDKIFDQMDKNHDGKLTLEEFRE 170
Cdd:cd15902    5 WMHFDADGNGYIEGKELDSFLRELLK--ALNGKDKTDDEVAEKKKEFMEKYDENEDGKIEIRELAN 68

serine/threonine protein phosphatase 2A regulatory subunit B"; Heterotrimeric serine/threonine protein phosphatase 2A (PP2A) consists of scaffolding (A), catalytic (C), and variable (B, B', and B") subunits. The variable subunits dictate subcellular localization and substrate specificity of the PP2A holoenzyme. This family includes PP2A regulatory B'' subunits alpha, beta and gamma, encoded by PPP2R3A, PPP2R3B and PPP2R3C, respectively. It also includes subunit delta encoded by PPP2R3D in mouse. These B-family regulatory subunits play various roles including regulation of cytoskeletal assembly, neuronal differentiation, mitogen-activated protein kinase signaling, and apoptosis. Subunits alpha and beta contain two-domain elongated structure with two calcium EF-hands which mediate Ca2+-dependent changes in phosphatase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  64 FASLVFRVFDENNDGSIEFEEFIRALSVTSKGNLDEKLQWAFRLYDVDNDGYITREEMYNIVDAIYQMV---GQQPQSEd 140
Cdd:cd21339  144 FSGAVTRGKTIQKEGEMSYADFVWFLISEEDKKEPTSIEYWFRCLDIDGDGYLSVFELEYFYEEQCERMkihGIEPLPF- 222

                         90       100
                 ....*....|....*....|....*....
gi 442616816 141 entpQKRVDKIFDQMDKNHDGKLTLEEFR 169
Cdd:cd21339  223 ----QDVLCQILDLVKPKDPGKITLQDLK 247

EF hand;

                          10        20
                  ....*....|....*....|...
gi 442616816  148 VDKIFDQMDKNHDGKLTLEEFRE 170
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRR 23

EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The family corresponds to a group of uncharacterized calglandulin-like proteins. Although their biological function remain unclear, they show high sequence similarity with human calglandulin-like protein GAGLP, which is an ortholog of calglandulin from the venom glands of Bothrops insularis snake. Both GAGLP and calglandulin are putative Ca2+-binding proteins with four EF-hand motifs. However, members in this family contain only three EF-hand motifs. In this point, they may belong to the parvalbumin-like EF-hand family, which is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  78 GSIEFEEFIRAL-SVTSKGNLDEKLQWAFRLYDVDNDGYITREEMYNIVDAIYQMVGQQPQSEDEntpqkrVDKIFDQMD 156
Cdd:cd16252   15 GSFNYSKFFEYMqKFQTSEQQEEAIRKAFQMLDKDKSGFIEWNEIKYILSTVPSSMPVAPLSDEE------AEAMIQAAD 88

                         90
                 ....*....|..
gi 442616816 157 KNHDGKLTLEEF 168
Cdd:cd16252   89 TDGDGRIDFQEF 100

EF-hand, calcium binding motif, found in calbindin (CB); CB, also termed calbindin D28, or D-28K, or avian-type vitamin D-dependent calcium-binding protein, is a unique intracellular calcium binding protein that functions as both a calcium sensor and buffer in eukaryotic cells, which undergoes a conformational change upon calcium binding and protects cells against insults of high intracellular calcium concentration. CB is highly expressed in brain and sensory neurons. It plays essential roles in neural functioning, altering synaptic interactions in the hippocampus, modulating calcium channel activity, calcium transients, and intrinsic neuronal firing activity. It prevents a neuronal death, as well as maintains and controls calcium homeostasis. CB also modulates the activity of proteins participating in the development of neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and bipolar disorder. Moreover, CB interacts with Ran-binding protein M, a protein known to involve in microtubule function. It also interacts with alkaline phosphatase and myo-inositol monophosphatase, as well as caspase 3, an enzyme that plays an important role in the regulation of apoptosis. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions with high affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442616816  32 KGFLKDcpngllteqgFIKIYKQFFPQGDPSKFASLVFRVFDENNDGSIEFEEFIRALSVtsKGNLDEKLQW-------- 103
Cdd:cd16176  108 KSFLKD----------LLKKANKPFDESKLEEYTHTMLKMFDSNNDGKLGLTEMARLLPV--QENFLLKFQGvkmcgkef 175

                         90       100
                 ....*....|....*....|
gi 442616816 104 --AFRLYDVDNDGYITREEM 121
Cdd:cd16176  176 nkIFELYDQDGNGYIDENEL 195

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 442616816  40 NGLLTEQGFIKIYKQFFPqGDPSKFASLVFRVFDENNDGSIEFEEFIRALS 90
Cdd:cd00051   14 DGTISADELKAALKSLGE-GLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63