NCBI Conserved Domain Search

calmodulin; Provisional

Pssm-ID: 185504 [Multi-domain] Cd Length: 149 Bit Score: 115.63 E-value: 2.05e-33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  20 ELGPEELDELQAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEMELLEVSQHIKMRMGGRVDFEEFVELIGPKLREETAH 99
Cdd:PTZ00184    4 QLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKDTDSE 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1824614785 100 mlgvRELRIAFREFDRDRDGRITVAELREaVPALLGEPLAGPELDEMLREVDLNGDGTVDFDEFV-MMLSR 169
Cdd:PTZ00184   84 ----EEIKEAFKVFDRDGNGFISAAELRH-VMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVkMMMSK 149

centrin; Provisional

Pssm-ID: 185503 [Multi-domain] Cd Length: 158 Bit Score: 93.99 E-value: 7.16e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  20 ELGPEELDELQAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEMELLEVSQHIKMRMGGRVDFEEFVELIGPKL-----R 94
Cdd:PTZ00183   10 GLTEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKLgerdpR 89

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1824614785  95 EETAHMlgvrelriaFREFDRDRDGRITVAELREaVPALLGEPLAGPELDEMLREVDLNGDGTVDFDEFVMMLSR 169
Cdd:PTZ00183   90 EEILKA---------FRLFDDDKTGKISLKNLKR-VAKELGETITDEELQEMIDEADRNGDGEISEEEFYRIMKK 154

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.

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 75.66 E-value: 7.22e-19

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1824614785 105 ELRIAFREFDRDRDGRITVAELREAVPALlGEPLAGPELDEMLREVDLNGDGTVDFDEFVMMLS 168
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSL-GEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 72.52 E-value: 9.48e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  24 EELDELQAAFEEFDTDRDGYISHRELGDCMRtlGYMPTEMELLEVSQHikmrmgGRVDFEEFVELIGPKLREETAhmlgv 103
Cdd:COG5126     2 LQRRKLDRRFDLLDADGDGVLERDDFEALFR--RLWATLFSEADTDGD------GRISREEFVAGMESLFEATVE----- 68

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1824614785 104 RELRIAFREFDRDRDGRITVAELREAVPALlgePLAGPELDEMLREVDLNGDGTVDFDEFV 164
Cdd:COG5126    69 PFARAAFDLLDTDGDGKISADEFRRLLTAL---GVSEEEADELFARLDTDGDGKISFEEFV 126

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+.

Pssm-ID: 320055 [Multi-domain] Cd Length: 164 Bit Score: 68.32 E-value: 5.63e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  28 ELQAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEMELLevsqHIKMRM-----GGRVDFEEFVELIGPklreetahmlg 102
Cdd:cd16180     1 ELRRIFQAVDRDRSGRISAKELQRALSNGDWTPFSIETV----RLMINMfdrdrSGTINFDEFVGLWKY----------- 65

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1824614785 103 VRELRIAFREFDRDRDGRITVAELREAVPAlLGEPLAGPELDEMLREVDLNGDGTVDFDEFVMML 167
Cdd:cd16180    66 IQDWRRLFRRFDRDRSGSIDFNELQNALSS-FGYRLSPQFVQLLVRKFDRRRRGSISFDDFVEAC 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+.

Pssm-ID: 320055 [Multi-domain] Cd Length: 164 Bit Score: 63.70 E-value: 3.24e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  24 EELDELQAAFEEFDTDRDGYISHRELGDCMRTLGY-MPTEMELLEVSQHIKmRMGGRVDFEEFVELigpklreetahMLG 102
Cdd:cd16180    64 KYIQDWRRLFRRFDRDRSGSIDFNELQNALSSFGYrLSPQFVQLLVRKFDR-RRRGSISFDDFVEA-----------CVT 131

                          90       100
                  ....*....|....*....|
gi 1824614785 103 VRELRIAFREFDRDRDGRIT 122
Cdd:cd16180   132 LKRLTDAFRKYDTNRTGYAT 151

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 60.73 E-value: 5.22e-13

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1824614785 105 ELRIAFREFDRDRDGRITVAELREAV-PALLGEPLAGPELDEMLREVDLNGDGTVDFDEFV 164
Cdd:pfam13499   3 KLKEAFKLLDSDGDGYLDVEELKKLLrKLEEGEPLSDEEVEELFKEFDLDKDGRISFEEFL 63

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).

Pssm-ID: 320060 [Multi-domain] Cd Length: 163 Bit Score: 59.54 E-value: 1.13e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  28 ELQAAFEEFDTDRDGYISHRELGDcMRTLGYMPTEMELleVSQHIKM---RMGGRVDFEEFVELigpklreetaH--MLG 102
Cdd:cd16185     1 ELRQWFRAVDRDRSGSIDVNELQK-ALAGGGLLFSLAT--AEKLIRMfdrDGNGTIDFEEFAAL----------HqfLSN 67

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1824614785 103 VRElriAFREFDRDRDGRITVAELREAVpALLGEPLAGPELDEMLREVDLNGDGTVDFDEFVMM 166
Cdd:cd16185    68 MQN---GFEQRDTSRSGRLDANEVHEAL-AASGFQLDPPAFQALFRKFDPDRGGSLGFDDYIEL 127

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.

Pssm-ID: 320075 [Multi-domain] Cd Length: 254 Bit Score: 56.21 E-value: 5.49e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  33 FEEFDTDRDGYISHRELGDCMRTL--GYMPTEMELLEVSQHIKMRMG-------GRVDFEEFVELIGP-----KLREETA 98
Cdd:cd15902     5 WMHFDADGNGYIEGKELDSFLRELlkALNGKDKTDDEVAEKKKEFMEkydenedGKIEIRELANILPTeenflLLFRREQ 84

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1824614785  99 HMLGVRELRIAFREFDRDRDGRITVAELREAVPALL---GEPLAGPELDE----MLREVDLNGDGTVDFDEFVMML 167
Cdd:cd15902    85 PLISSVEFMKIWRKYDTDGSGFIEAKELKGFLKDLLlknKKHVSPPKLDEytklILKEFDANKDGKLELDEMAKLL 160

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.

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 52.16 E-value: 8.30e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1824614785  28 ELQAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEMELLEVsqhikMRMG-----GRVDFEEFVELI 89
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEM-----IREVdkdgdGKIDFEEFLELM 62

centrin; Provisional

Pssm-ID: 185503 [Multi-domain] Cd Length: 158 Bit Score: 48.53 E-value: 1.35e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1824614785 105 ELRIAFREFDRDRDGRITVAELREAVPALLGEPlAGPELDEMLREVDLNGDGTVDFDEFVMMLSRH 170
Cdd:PTZ00183   18 EIREAFDLFDTDGSGTIDPKELKVAMRSLGFEP-KKEEIKQMIADVDKDGSGKIDFEEFLDIMTKK 82

EF-hand domain pair;

Pssm-ID: 404678 [Multi-domain] Cd Length: 54 Bit Score: 45.77 E-value: 1.58e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1824614785 118 DGRITVAELREAVPALLGEPLAGPELDEMLREVDLNGDGTVDFDEFVMMLSR 169
Cdd:pfam13833   2 KGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLLER 53

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 47.86 E-value: 1.66e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1824614785 101 LGVRELRIAFREFDRDRDGRITVAELREAVPALLgEPLAGPELDEMLREVDLNGDGTVDFDEFVMMLS 168
Cdd:COG5126    30 LFRRLWATLFSEADTDGDGRISREEFVAGMESLF-EATVEPFARAAFDLLDTDGDGKISADEFRRLLT 96

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 47.48 E-value: 2.06e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  29 LQAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEMELLEVSQHIKMRMGGRVDFEEFVELIgpklreeTAHMLGVRELRI 108
Cdd:COG5126    35 WATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLL-------TALGVSEEEADE 107

                          90       100
                  ....*....|....*....|..
gi 1824614785 109 AFREFDRDRDGRITVAELREAV 130
Cdd:COG5126   108 LFARLDTDGDGKISFEEFVAAV 129

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.

Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 47.28 E-value: 2.84e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1824614785 106 LRIAFREFDRDRDGRITVAELREAVPALLGePLAGPELDEMLREVDLNGDGTVDFDEFVMMLSRH 170
Cdd:cd15898     2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNI-RVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSL 65

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).

Pssm-ID: 320060 [Multi-domain] Cd Length: 163 Bit Score: 47.59 E-value: 2.99e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  29 LQAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEMELLEVSQHIKMRMGGRVDFEEFVELigpklreeTAHMLGVRELri 108
Cdd:cd16185    68 MQNGFEQRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFDPDRGGSLGFDDYIEL--------CIFLASARNL-- 137

                          90
                  ....*....|....*
gi 1824614785 109 aFREFDRDRDGRITV 123
Cdd:cd16185   138 -FQAFDRQRTGRVTL 151

The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five EF-hand calcium-binding proteins, including several classical calpain large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14), two calpain small subunits (CAPNS1 and CAPNS2), as well as non-calpain PEF proteins, ALG-2 (apoptosis-linked gene 2, also termed programmed cell death protein 6, PDCD6), peflin, sorcin, and grancalcin. Based on the sequence similarity of EF1 hand, ALG-2 and peflin have been classified into group I PEF proteins. Calcium-dependent protease calpain subfamily members, sorcin and grancalcin, are group II PEF proteins. Calpains (EC 3.4.22.17) are calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates. They have been implicated in a number of physiological processes such as cell cycle progression, remodeling of cytoskeletal-cell membrane attachments, signal transduction, gene expression and apoptosis. ALG-2 is a pro-apoptotic factor that forms a homodimer in the cell or a heterodimer with its closest paralog peflin through their EF5s. Peflin is a 30-kD PEF protein with a longer N-terminal hydrophobic domain than any other member of the PEF family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. It exists only as a heterodimer with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. ALG-2 interacts with various proteins in a Ca2+-dependent manner. Sorcin (for soluble resistance-related calcium binding protein) is a soluble resistance-related calcium-binding protein that participates in the regulation of calcium homeostasis in cells. Grancalcin is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It plays a key role in leukocyte-specific functions that are responsible for host defense. Grancalcin can form a heterodimer together with sorcin. Members in this family contain five EF-hand motifs attached to an N-terminal region of variable length containing one or more short Gly/Pro-rich sequences. These proteins form homodimers or heterodimers through pairing between the 5th EF-hands from the two molecules. Unlike calmodulin, the PEF domains do not undergo major conformational changes upon binding Ca2+.

Pssm-ID: 320054 [Multi-domain] Cd Length: 165 Bit Score: 47.43 E-value: 3.13e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  20 ELGPEELDEL-------QAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEmellEVSQHIKMRMG---GRVDFEEFVELi 89
Cdd:cd15897    56 KLNFSEFKGLwnyikawQEIFRTYDTDGSGTIDSNELRQALSGAGYRLSE----QTYDIIIRRYDrgrGNIDFDDFIQC- 130

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1824614785  90 gpklreetahMLGVRELRIAFREFDRDRDGRITV 123
Cdd:cd15897   131 ----------CVRLQRLTDAFRRYDKDQDGQIQV 154

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.

Pssm-ID: 320078 [Multi-domain] Cd Length: 257 Bit Score: 47.40 E-value: 8.08e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  33 FEEFDTDRDGYISHRELGDCMRTLGYMPTEMELLEVSQHIKMR---MG-------GRVDFEEFVELIGPK-------LRE 95
Cdd:cd16178     5 WQHFDADESGYIEGKELDNFFKDLLKKLGTKDTISADEVQDVKecfMSaydvtgdGRIQIQELANIILPDdenfllfFRR 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  96 ETAHMLGVRELRIaFREFDRDRDGRITVAELREAVPALL---GEPLAGPELDE----MLREVDLNGDGTVDFDEFVMMLS 168
Cdd:cd16178    85 EEPLDSSVEFMRI-WRKYDADSSGYISAAELKNFLRDLFlqhKKVITEDKLDEytdtMMKIFDKNKDGRLDLNDMARILA 163

The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five EF-hand calcium-binding proteins, including several classical calpain large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14), two calpain small subunits (CAPNS1 and CAPNS2), as well as non-calpain PEF proteins, ALG-2 (apoptosis-linked gene 2, also termed programmed cell death protein 6, PDCD6), peflin, sorcin, and grancalcin. Based on the sequence similarity of EF1 hand, ALG-2 and peflin have been classified into group I PEF proteins. Calcium-dependent protease calpain subfamily members, sorcin and grancalcin, are group II PEF proteins. Calpains (EC 3.4.22.17) are calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates. They have been implicated in a number of physiological processes such as cell cycle progression, remodeling of cytoskeletal-cell membrane attachments, signal transduction, gene expression and apoptosis. ALG-2 is a pro-apoptotic factor that forms a homodimer in the cell or a heterodimer with its closest paralog peflin through their EF5s. Peflin is a 30-kD PEF protein with a longer N-terminal hydrophobic domain than any other member of the PEF family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. It exists only as a heterodimer with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. ALG-2 interacts with various proteins in a Ca2+-dependent manner. Sorcin (for soluble resistance-related calcium binding protein) is a soluble resistance-related calcium-binding protein that participates in the regulation of calcium homeostasis in cells. Grancalcin is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It plays a key role in leukocyte-specific functions that are responsible for host defense. Grancalcin can form a heterodimer together with sorcin. Members in this family contain five EF-hand motifs attached to an N-terminal region of variable length containing one or more short Gly/Pro-rich sequences. These proteins form homodimers or heterodimers through pairing between the 5th EF-hands from the two molecules. Unlike calmodulin, the PEF domains do not undergo major conformational changes upon binding Ca2+.

Pssm-ID: 320054 [Multi-domain] Cd Length: 165 Bit Score: 46.27 E-value: 1.08e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  28 ELQAAFEEFDTDrDGYISHRELGDCMRTLGYMPTEMELLEVSQHIKMRM-----GGRVDFEEFVELigpklreeTAHMLG 102
Cdd:cd15897     1 QLRNVFQAVAGD-DGEISATELQQALSNVGWTHFDLGFSLETCRSMIAMmdrdhSGKLNFSEFKGL--------WNYIKA 71

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1824614785 103 VRELriaFREFDRDRDGRITVAELREAVpALLGEPLAGPELDEMLREVDlNGDGTVDFDEFV 164
Cdd:cd15897    72 WQEI---FRTYDTDGSGTIDSNELRQAL-SGAGYRLSEQTYDIIIRRYD-RGRGNIDFDDFI 128

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.

Pssm-ID: 320057 [Multi-domain] Cd Length: 167 Bit Score: 45.68 E-value: 1.35e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  78 GRVDFEEFVELigpklreetahMLGVRELRIAFREFDRDRDGRITVAELREAVPAllgeplAGPELDE------MLREVD 151
Cdd:cd16182    57 GRLDLEEFKTL-----------WSDLKKWQAIFKKFDTDRSGTLSSYELRKALES------AGFHLSNkvlqalVLRYAD 119

                          90
                  ....*....|....*...
gi 1824614785 152 lnGDGTVDFDEFVMMLSR 169
Cdd:cd16182   120 --STGRITFEDFVSCLVR 135

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.

Pssm-ID: 197492 [Multi-domain] Cd Length: 29 Bit Score: 42.75 E-value: 1.56e-06

                           10        20
                   ....*....|....*....|....*...
gi 1824614785  142 ELDEMLREVDLNGDGTVDFDEFVMMLSR 169
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKA 28

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).

Pssm-ID: 320025 [Multi-domain] Cd Length: 263 Bit Score: 46.16 E-value: 2.06e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  25 ELDELQAA--FEEFDTDRDGYISHRELgdCMRTLGYMPTEME----------LLEVSQHIKMRMG------GRVDFEEFV 86
Cdd:cd16227    68 MLDEEEANerFEEADEDGDGKVTWEEY--LADSFGYDDEDNEemikdsteddLKLLEDDKEMFEAadlnkdGKLDKTEFS 145

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1824614785  87 ELIGPklrEETAHMLGVrELRIAFREFDRDRDGRITVAE-LREAVPALLGEPLAgPELDEMLREVDLNGDGTVDFDE 162
Cdd:cd16227   146 AFQHP---EEYPHMHPV-LIEQTLRDKDKDNDGFISFQEfLGDRAGHEDKEWLL-VEKDRFDEDYDKDGDGKLDGEE 217

Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The family corresponds to the second group of penta-EF hand (PEF) proteins that includes sorcin, grancalcin, and similar proteins. Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. It contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH. Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It can strongly interact with sorcin to form a heterodimer and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. In contrast with sorcin, GCA binds two Ca2+ ions through its EF1 and EF3 hands.

Pssm-ID: 320056 [Multi-domain] Cd Length: 165 Bit Score: 45.05 E-value: 2.26e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  21 LGPEELDELQAA-------FEEFDTDRDGYISHRELGDCMRTLGY--MPTEMELLeVSQHIKmrmGGRVDFEEFVELIgP 91
Cdd:cd16181    57 MGFNEFKELWAAlnqwkttFMQYDRDRSGTVEPQELQQAIRSFGYnlSPQALNVI-VKRYSK---NGRITFDDFVACA-V 131

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1824614785  92 KLREETAHmlgvrelriaFREFDRDRDGRIT 122
Cdd:cd16181   132 RLRALTDR----------FRRRDTQQNGTAT 152

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. 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.

Pssm-ID: 320058 [Multi-domain] Cd Length: 165 Bit Score: 45.32 E-value: 2.34e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  28 ELQAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEMELlevsqhIKMRMG-------GRVDFEEFVELIgpKLreetahm 100
Cdd:cd16183     1 FLWNVFQRVDKDRSGQISATELQQALSNGTWTPFNPET------VRLMIGmfdrdnsGTINFQEFAALW--KY------- 65

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1824614785 101 lgVRELRIAFREFDRDRDGRITVAELREAVPAlLGEPLAGPELDEMLREVDLNGDGTVDFDEFV 164
Cdd:cd16183    66 --ITDWQNCFRSFDRDNSGNIDKNELKQALTS-FGYRLSDQFYDILVRKFDRQGRGTIAFDDFI 126

Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The family corresponds to the second group of penta-EF hand (PEF) proteins that includes sorcin, grancalcin, and similar proteins. Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. It contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH. Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It can strongly interact with sorcin to form a heterodimer and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. In contrast with sorcin, GCA binds two Ca2+ ions through its EF1 and EF3 hands.

Pssm-ID: 320056 [Multi-domain] Cd Length: 165 Bit Score: 45.05 E-value: 2.55e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  40 RDGYISHRELGDCMRTLG----YMPTEMELLEVSqhIKM---RMGGRVDFEEFVELIGpklreetahmlGVRELRIAFRE 112
Cdd:cd16181    12 QDGQIDADELQRCLTQSGisgnYQPFSLETCRLM--IAMldrDHSGKMGFNEFKELWA-----------ALNQWKTTFMQ 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1824614785 113 FDRDRDGRITVAELREAVpALLGEPLAGPELDEMLREVDLNgdGTVDFDEFV 164
Cdd:cd16181    79 YDRDRSGTVEPQELQQAI-RSFGYNLSPQALNVIVKRYSKN--GRITFDDFV 127

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.

Pssm-ID: 425435 [Multi-domain] Cd Length: 29 Bit Score: 41.23 E-value: 5.22e-06

                          10        20
                  ....*....|....*....|....*...
gi 1824614785 142 ELDEMLREVDLNGDGTVDFDEFVMMLSR 169
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKK 28

EF-hand domain;

Pssm-ID: 463869 [Multi-domain] Cd Length: 30 Bit Score: 40.62 E-value: 7.84e-06

                          10        20        30
                  ....*....|....*....|....*....|
gi 1824614785  28 ELQAAFEEFDTDRDGYISHRELGDCMRTLG 57
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. 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.

Pssm-ID: 320058 [Multi-domain] Cd Length: 165 Bit Score: 43.78 E-value: 8.37e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  30 QAAFEEFDTDRDGYISHRELGDCMRTLGYmptemELLEVSQHIKMRM-----GGRVDFEEFVeligpklreETAHMLgvR 104
Cdd:cd16183    70 QNCFRSFDRDNSGNIDKNELKQALTSFGY-----RLSDQFYDILVRKfdrqgRGTIAFDDFI---------QCCVVL--Q 133

                          90
                  ....*....|....*....
gi 1824614785 105 ELRIAFREFDRDRDGRITV 123
Cdd:cd16183   134 TLTDSFRRYDTDQDGWIQI 152

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.

Pssm-ID: 197492 [Multi-domain] Cd Length: 29 Bit Score: 40.44 E-value: 1.15e-05

                           10        20
                   ....*....|....*....|....*....
gi 1824614785   28 ELQAAFEEFDTDRDGYISHRELGDCMRTL 56
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

phosphatidylserine decarboxylase

Pssm-ID: 215520 [Multi-domain] Cd Length: 644 Bit Score: 44.08 E-value: 1.50e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1824614785  94 REETAHMLGVRELRIAfrefDRDRDGRITVAELREAVPALlGEPLAGPELDEMLREVDLNGDGTVDFDEFVMMLSRH 170
Cdd:PLN02964  173 PVETERSFARRILAIV----DYDEDGQLSFSEFSDLIKAF-GNLVAANKKEELFKAADLNGDGVVTIDELAALLALQ 244

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).

Pssm-ID: 319995 [Multi-domain] Cd Length: 106 Bit Score: 41.75 E-value: 1.50e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  74 MRMGGRVDFEEFVELI----GPKLREETahmlgvreLRIAFREFDRDRDGRITVAELR---EAVP-ALLGEPLAGPELDE 145
Cdd:cd16252    11 MRHHGSFNYSKFFEYMqkfqTSEQQEEA--------IRKAFQMLDKDKSGFIEWNEIKyilSTVPsSMPVAPLSDEEAEA 82

                          90       100
                  ....*....|....*....|....
gi 1824614785 146 MLREVDLNGDGTVDFDEFVMMLSR 169
Cdd:cd16252    83 MIQAADTDGDGRIDFQEFSDMVKK 106

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.

Pssm-ID: 238009 [Multi-domain] Cd Length: 67 Bit Score: 41.05 E-value: 1.54e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1824614785 110 FREFDRDRDGRITVAElreAVPALLGEPLAGPELDEMLREVDLNGDGTVDFDEFV 164
Cdd:cd00052     5 FRSLDPDGDGLISGDE---ARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFA 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.

Pssm-ID: 320075 [Multi-domain] Cd Length: 254 Bit Score: 43.11 E-value: 2.20e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  16 LQDRELGPEELD-ELQAAFEEFDTDRDGYISHRELGDCMRTLGYM-PTEMELLEVSQHIKMRM-------GGRVDFEEFV 86
Cdd:cd15902    78 LLFRREQPLISSvEFMKIWRKYDTDGSGFIEAKELKGFLKDLLLKnKKHVSPPKLDEYTKLILkefdankDGKLELDEMA 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  87 ELIGPKLRE-ETAHMLGVRELR-----IAFREFDRDRDGRITVAELREAVPALLGEPLAGPELDEM-------LREVDLN 153
Cdd:cd15902   158 KLLPVQENFlLKFQILGAMDLTkedfeKVFEHYDKDNNGVIEGNELDALLKDLLEKNKADIDKPDLenfrdaiLRACDKN 237

                         170
                  ....*....|....*
gi 1824614785 154 GDGTVDFDEFVMMLS 168
Cdd:cd15902   238 KDGKIQKTELALFLS 252

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.

Pssm-ID: 425435 [Multi-domain] Cd Length: 29 Bit Score: 38.92 E-value: 3.65e-05

                          10        20
                  ....*....|....*....|....*....
gi 1824614785  28 ELQAAFEEFDTDRDGYISHRELGDCMRTL 56
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29

EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, 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 possibly functions as a calcium buffer, calcium sensor, and apoptosis regulator, which may be implicated in many biological processes, including cell proliferation, differentiation, and cell death. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. CR I-II consists of EF-hand motifs 1 and 2, and CR III-VI consists of EF-hand motifs 3-6. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. Thus, CR has two pairs of cooperative binding sites (I-II and III-IV), which display high affinity calcium-binding sites, and one independent calcium ion-binding site (V), which displays lower affinity binding.

Pssm-ID: 320077 [Multi-domain] Cd Length: 248 Bit Score: 42.55 E-value: 3.95e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  33 FEEFDTDRDGYISHRELGDCMRTL-------GYMPT----EMELLEVSQHIKMRMGGRVDFEEFVELigpkLREETAHML 101
Cdd:cd16177     5 WKHFDADGNGYIEGKELENFFRELerarrgaGVDSKsanfGEKMKEFMQKYDKNADGRIEMAELAQI----LPTEENFLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785 102 GVR-------ELRIAFREFDRDRDGRITVAELREAVPALL---GEPLAGPELDE----MLREVDLNGDGTVDFDEFVMML 167
Cdd:cd16177    81 CFRqhvgsssEFMEAWRKYDTDRSGYIEANELKGFLSDLLkkaNRPYDEKKLQEytqtILRMFDLNGDGKLGLSEMARLL 160

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.

Pssm-ID: 320021 [Multi-domain] Cd Length: 267 Bit Score: 42.43 E-value: 3.97e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  11 SWTLPLQDRElgpeELDELQAAFEEFDTDRDGYISHRELGDCMrtlgymptemellevsqhikmrMGGRVDFEEFVELiG 90
Cdd:cd15899    59 SWILESFKRH----AMEESKEQFRAVDPDEDGHVSWDEYKNDT----------------------YGSVGDDEENVAD-N 111

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1824614785  91 PKLREETAHMLGVRELRiaFREFDRDRDGRITVAELR-----EAVPALLGEPLAgpeldEMLREVDLNGDGTVDFDEFV 164
Cdd:cd15899   112 IKEDEEYKKLLLKDKKR--FEAADQDGDLILTLEEFLaflhpEESPYMLDFVIK-----ETLEDLDKNGDGFISLEEFI 183

S-100: S-100 domain, which represents the largest family within the superfamily of proteins carrying the Ca-binding EF-hand motif. Note that this S-100 hierarchy contains only S-100 EF-hand domains, other EF-hands have been modeled separately. S100 proteins are expressed exclusively in vertebrates, and are implicated in intracellular and extracellular regulatory activities. Intracellularly, S100 proteins act as Ca-signaling or Ca-buffering proteins. The most unusual characteristic of certain S100 proteins is their occurrence in extracellular space, where they act in a cytokine-like manner through RAGE, the receptor for advanced glycation products. Structural data suggest that many S100 members exist within cells as homo- or heterodimers and even oligomers; oligomerization contributes to their functional diversification. Upon binding calcium, most S100 proteins change conformation to a more open structure exposing a hydrophobic cleft. This hydrophobic surface represents the interaction site of S100 proteins with their target proteins. There is experimental evidence showing that many S100 proteins have multiple binding partners with diverse mode of interaction with different targets. In addition to S100 proteins (such as S100A1,-3,-4,-6,-7,-10,-11,and -13), this group includes the ''fused'' gene family, a group of calcium binding S100-related proteins. The ''fused'' gene family includes multifunctional epidermal differentiation proteins - profilaggrin, trichohyalin, repetin, hornerin, and cornulin; functionally these proteins are associated with keratin intermediate filaments and partially crosslinked to the cell envelope. These ''fused'' gene proteins contain N-terminal sequence with two Ca-binding EF-hands motif, which may be associated with calcium signaling in epidermal cells and autoprocessing in a calcium-dependent manner. In contrast to S100 proteins, "fused" gene family proteins contain an extraordinary high number of almost perfect peptide repeats with regular array of polar and charged residues similar to many known cell envelope proteins.

Pssm-ID: 238131 [Multi-domain] Cd Length: 88 Bit Score: 40.17 E-value: 4.33e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1824614785 117 RDGRITVAELREAV----PALLGEPLAGPELDEMLREVDLNGDGTVDFDEFVMML 167
Cdd:cd00213    23 DKDTLSKKELKELLetelPNFLKNQKDPEAVDKIMKDLDVNKDGKVDFQEFLVLI 77

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.

Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 40.73 E-value: 7.37e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  29 LQAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEMELLEVSQHIKMRMGGRVDFEEFVELIgpklreetaHMLGVR-ELR 107
Cdd:cd15898     2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELY---------KSLTERpELE 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1824614785 108 IAFREFDRDRDGRITVAELREAVPALLGEPLAGPELDEMLREVDLNG-DGTVDFDEFVMMLS 168
Cdd:cd15898    73 PIFKKYAGTNRDYMTLEEFIRFLREEQGENVSEEECEELIEKYEPEReNRQLSFEGFTNFLL 134

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 39.16 E-value: 7.71e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  27 DELQAAFEEFDTDRDGYISHRELGDCMRTLGYM--PTEMELLEVsqhikMRM-----GGRVDFEEFVELI 89
Cdd:pfam13499   2 EKLKEAFKLLDSDGDGYLDVEELKKLLRKLEEGepLSDEEVEEL-----FKEfdldkDGRISFEEFLELY 66

Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed calcium-activated neutral proteinase 12 (CANP 12), is a calpain large subunit mainly expressed in the cortex of the hair follicle. It may affect apoptosis regulation. CAPN12 contains 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.

Pssm-ID: 320069 [Multi-domain] Cd Length: 169 Bit Score: 40.25 E-value: 1.27e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  17 QDRELGPEELDELQAAFEEFDTDRDgyishrelgdcmrtlgymPTEMELLEVSQHIKM---RMGGRVDFEEFVELIGpKL 93
Cdd:cd16194    12 EDEEINASELQKILSIALERAHTSK------------------PREFGLRTCRQLIQCfdhGQNGKLALEEFQQLWG-YL 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1824614785  94 REETAhmlgvrelriAFREFDRDRDGRITVAELREAVPAllgeplAGPELDEMLREVDLNGDGT----VDFDEFVMMLS 168
Cdd:cd16194    73 LEWQA----------IFTKFDEDTSGTMDSYELRLALNA------AGFHLNNQLTETLTSRYRDsrlrVDFESFLSCLA 135

EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes alpha- and beta-parvalbumins, and a group of uncharacterized calglandulin-like proteins. Parvalbumins are small, acidic, cytosolic EF-hand-containing Ca2+-buffer and Ca2+ transporter/shuttle proteins belonging to EF-hand superfamily. They are expressed by vertebrates in fast-twitch muscle cells, specific neurons of the central and peripheral nervous system, sensory cells of the mammalian auditory organ (Corti's cell), and some other cells, and characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Thus, they may play an additional role in Mg2+ handling. Moreover, parvalbumins represent one of the major animal allergens. In metal-bound states, parvalbumins possess a rigid and stable tertiary structure and display strong allergenicity. In contrast, the metal-free parvalbumins are intrinsically disordered, and the loss of metal ions results in a conformational change that decreases their IgE binding capacity. Furthermore, parvalbumins have been widely used as a neuronal marker for a variety of functional brain systems. They also function as a Ca2+ shuttle transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus they may facilitate myocardial relaxation and play important roles in cardiac diastolic dysfunction. Parvalbumins consists of alpha- and beta- sublineages, which can be distinguished on the basis of isoelectric point (pI > 5 for alpha; pI

Pssm-ID: 319994 [Multi-domain] Cd Length: 101 Bit Score: 38.67 E-value: 1.94e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  74 MRMGGRVDFEEFVELIGPKLREETahmlgvrELRIAFREFDRDRDGRITVAELREAvpaLLGEPLAGPELDE-----MLR 148
Cdd:cd16251    11 FRAHGSFNYKKFFEHVGLKQKSED-------QIKKVFQILDKDKSGFIEEEELKYI---LKGFSIAGRDLTDeetkaLLA 80

                          90
                  ....*....|....*...
gi 1824614785 149 EVDLNGDGTVDFDEFVMM 166
Cdd:cd16251    81 AGDTDGDGKIGVEEFATL 98

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.

Pssm-ID: 425435 [Multi-domain] Cd Length: 29 Bit Score: 36.61 E-value: 2.45e-04

                          10        20
                  ....*....|....*....|....*.
gi 1824614785 105 ELRIAFREFDRDRDGRITVAELREAV 130
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELL 26

EF-hand domain;

Pssm-ID: 463869 [Multi-domain] Cd Length: 30 Bit Score: 36.77 E-value: 2.54e-04

                          10        20
                  ....*....|....*....|....*.
gi 1824614785 105 ELRIAFREFDRDRDGRITVAELREAV 130
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKAL 26

N-terminal domain of Myosin essential light chain ELC; ELC is part of the apicomplexan membrane-associated protein complex called the glideosome, which is essential for parasite motility. The glideosome is composed of six proteins: myosin A (MyoA), essential light chain ELC, myosin light chain MLC1 (also called MTIP), and the glideosome-associated proteins GAP40, GAP45, and GAP50. MyoA is a Class XIV myosin implicated in gliding motility, as well as host cell and tissue invasion by parasites. ELC binds to the MyoA neck region adjacent to the MLC1-binding site, and both myosin light chains co-located to the glideosome. Although ELCs bind to a conserved MyoA sequence, P. falciparum ELC adopts a distinct structure in the free and MyoA-bound state. Therefore ELCs enhance MyoA performance by inducing alpha helical structure formation in MyoA and thus stiffening its lever arm. It has been shown that disruption of MyoA, MLC1, or ELC have dramatic effects on parasite motility but do not affect parasite shape or replication. The ELC N-terminal domain is part of the EF-hand calcium binding motif superfamily. Calcium binding has no effect on the structure of ELCs.

Pssm-ID: 439385 [Multi-domain] Cd Length: 66 Bit Score: 37.33 E-value: 2.93e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  27 DELQAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEMELLEVSQHIKMRmggrvDFEEFV 86
Cdd:cd22949     3 EKFREAFILFDRDGDGELTMYEAVLAMRSCGIPLTNDEKDALPASMNWD-----QFENWA 57

Calgranulins: S-100 domain found in proteins belonging to the Calgranulin subgroup of the S100 family of EF-hand calcium-modulated proteins, including S100A8, S100A9, and S100A12 . Note that the S-100 hierarchy, to which this Calgranulin group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. These proteins are expressed mainly in granulocytes, and are involved in inflammation, allergy, and neuritogenesis, as well as in host-parasite response. Calgranulins are modulated not only by calcium, but also by other metals such as zinc and copper. Structural data suggested that calgranulins may exist in multiple structural forms, homodimers, as well as hetero-oligomers. For example, the S100A8/S100A9 complex called calprotectin plays important roles in the regulation of inflammatory processes, wound repair, and regulating zinc-dependent enzymes as well as microbial growth.

Pssm-ID: 240156 [Multi-domain] Cd Length: 88 Bit Score: 37.33 E-value: 4.47e-04

                          10        20
                  ....*....|....*....|....*..
gi 1824614785 143 LDEMLREVDLNGDGTVDFDEFVMMLSR 169
Cdd:cd05030    53 IDKIFEDLDTNQDGQLSFEEFLVLVIK 79

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.

Pssm-ID: 320079 [Multi-domain] Cd Length: 261 Bit Score: 38.93 E-value: 7.25e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  28 ELQAAFEEFDTDRDGYISHRELGDCMRTL------GYMPTEMELLEVSQHI----KMRMGGRVDFEEFVELIgpKLRE-- 95
Cdd:cd16179    96 EFMKVWREYDKDNSGYIEADELKNFLKHLlkeakrDNDVSEDKLIEYTDTIlqlfDRNKDGKLQLSEMARLL--PVKEnf 173

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  96 ------ETAHMLGVRELRIAFREFDRDRDGRITVAELREAVPALL---GEPLAGPELDEM----LREVDLNGDGTVDFDE 162
Cdd:cd16179   174 lcrpifKGAGKLTREDIDRVFALYDRDNNGTIENEELTGFLKDLLelvQEDYDEQDLEEFkeiiLRGWDFNNDGKISRKE 253


                  ....*
gi 1824614785 163 FVMML 167
Cdd:cd16179   254 LTMLL 258

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.

Pssm-ID: 197492 [Multi-domain] Cd Length: 29 Bit Score: 35.43 E-value: 8.35e-04

                           10        20
                   ....*....|....*....|....*....
gi 1824614785  105 ELRIAFREFDRDRDGRITVAELREAVPAL 133
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit CAPNS1 and CAPNS2; CAPNS1, also termed calpain small subunit 1 (CSS1), or calcium-activated neutral proteinase small subunit (CANP small subunit), or calcium-dependent protease small subunit (CDPS), or calpain regulatory subunit, is a common 28-kDa regulatory calpain subunit encoded by the calpain small 1 (Capns1, also known as Capn4) gene. It acts as a binding partner to form a heterodimer with the 80 kDa calpain large catalytic subunit and is required in maintaining the activity of calpain. CAPNS1 plays a significant role in tumor progression of human cancer, and functions as a potential therapeutic target in human hepatocellular carcinoma (HCC), nasopharyngeal carcinoma (NPC), glioma, and clear cell renal cell carcinoma (ccRCC). It may be involved in regulating migration and cell survival through binding to the SH3 domain of Ras GTPase-activating protein (RasGAP). It may also modulate Akt/FoxO3A signaling and apoptosis through PP2A. CAPNS1 contains an N-terminal glycine rich domain and a C-terminal PEF-hand domain. CAPNS2, also termed calpain small subunit 2 (CSS2), is a novel tissue-specific 30 kDa calpain small subunit that lacks two oligo-Gly stretches characteristic of the N-terminal Gly-rich domain of CAPNS1. CAPNS2 acts as a chaperone for the calpain large subunit, and appears to be the functional equivalent of CAPNS1. However, CAPNS2 binds the large subunit much more weakly than CAPNS1 and it does not undergo the autolytic conversion typical of CAPNS1.

Pssm-ID: 320063 [Multi-domain] Cd Length: 169 Bit Score: 37.80 E-value: 9.83e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  20 ELGPEELDEL-------QAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEmELLEVSQHIKMRMGGRVDFEEFVELIgpk 92
Cdd:cd16188    59 KLGFEEFKYLwnnikkwQGIYKQFDTDRSGTIGSQELPGAFEAAGFHLNE-QLYQMIIRRYSDEDGNMDFDNFISCL--- 134

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1824614785  93 lreetahmlgVR--ELRIAFREFDRDRDGRITV 123
Cdd:cd16188   135 ----------VRldAMFRAFKSLDKDGTGQIQV 157

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), calpain-B (CalpB), and similar proteins; The family contains two calpains that have been found in Drosophila, CalpA and CalpB. CalpA, also termed calcium-activated neutral proteinase A (CANP A), or calpain-A catalytic subunit, is a Drosophila calpain homolog specifically expressed in a few neurons in the central nervous system, in scattered endocrine cells in the midgut, and in blood cells. CalpB, also termed calcium-activated neutral proteinase B (CANP B), contains calpain-B catalytic subunit 1 and calpain-B catalytic subunit 2. Both CalpA and CalpB are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. Besides, CalpA and CalpB display some distinguishing structural features that are not found in mammalian typical calpains. CalpA harbors a 76 amino acid long hydrophobic stretch inserted in domain IV, which may be involved in membrane attachment of this enzyme. CalpB has an unusually long N-terminal tail of 224 amino acids, which belongs to the class of intrinsically unstructured proteins (IUP) and may become ordered upon binding to target protein(s). Moreover, they do not need small regulatory subunits for their catalytic activity, and their proteolytic function is not regulated by an intrinsic inhibitor as the Drosophila genome contains neither regulatory subunit nor calpastatin orthologs. As a result, they may exist as a monomer or perhaps as a homo- or heterodimer together with a second large subunit. Furthermore, both CalpA and CalpB are dispensable for viability and fertility and do not share vital functions during Drosophila development. Phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol, and phosphatidic acid can stimulate the activity and the rate of activation of CalpA, but not CalpB. Calpain A modulates Toll responses by limited Cactus/IkappaB proteolysis. CalpB directly interacts with talin, an important component of the focal adhesion complex, and functions as an important modulator in border cell migration within egg chambers, which may act via the digestion of talin. CalpB can be phosphorylated by cAMP-dependent protein kinase (protein kinase A, PKA; EC 2.7.11.11) at Ser240 and Ser845, as well as by mitogen-activated protein kinase (ERK1 and ERK2; EC 2.7.11.24) at Thr747. The activation of the ERK pathway by extracellular signals results in the phosphorylation and activation of calpain B. In Schneider cells (S2), calpain B was mainly in the cytoplasm and upon a rise in Ca2+ the enzyme adhered to intracellular membranes.

Pssm-ID: 320071 [Multi-domain] Cd Length: 167 Bit Score: 37.95 E-value: 1.02e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  76 MGGRVDFEEFVELIGpklreetahmlgvrELRI---AFREFDRDRDGRITVAELREAVPAllgeplAGPELDE------M 146
Cdd:cd16196    54 RSGKLGFEEFKKLWE--------------DLRSwkrVFKLFDTDGSGSFSSFELRNALNS------AGFRLSNatlnalV 113

                          90       100
                  ....*....|....*....|...
gi 1824614785 147 LREVdlNGDGTVDFDEFVMMLSR 169
Cdd:cd16196   114 LRYS--NKDGRISFDDFIMCAVK 134

Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. The up-regulation of sorcin is correlated with a number of cancer types, including colorectal, gastric and breast cancer. It may represent a therapeutic target for reversing tumor multidrug resistance (MDR). Sorcin participates in the regulation of calcium homeostasis in cells and is necessary for the activation of mitosis and cytokinesis. It enhances metastasis and promotes epithelial-to-mesenchymal transition of colorectal cancer. Moreover, sorcin has been implicated in the regulation of intracellular Ca2+ cycling and cardiac excitation-contraction coupling. It displays the anti-apoptotic properties via the modulation of mitochondrial Ca2+ handling in cardiac myocytes. It can target and activate the sarcolemmal Na+/Ca2+ exchanger (NCX1) in cardiac muscle. Meanwhile, sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit. It also associates with calcium/calmodulin-dependent protein kinase IIdeltaC (CaMKIIdelta(C)) and further modulates ryanodine receptor (RyR) function in cardiac myocytes. Furthermore, sorcin may act as a Ca2+ sensor for glucose-induced nuclear translocation and the activation of carbohydrate-responsive element-binding protein (ChREBP)-dependent genes. As a mitochondrial chaperone TRAP1 interactor, sorcin involves in mitochondrial metabolism through the TRAP1 pathway. In addition, sorcin may regulate the inhibition of type I interferon response in cells through interacting with foot-and-mouth disease virus (FMDV) VP1. Sorcin contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH.

Pssm-ID: 320062 [Multi-domain] Cd Length: 165 Bit Score: 37.58 E-value: 1.09e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  40 RDGYISHRELGDCMRTLG----YMPTEMEL--LEVSQhIKMRMGGRVDFEEFVELigpklreetahMLGVRELRIAFREF 113
Cdd:cd16187    12 QDGQIDADELQRCLTQSGiaggYKPFNLETcrLMISM-LDRDMSGTMGFNEFKEL-----------WAVLNGWRQHFISF 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1824614785 114 DRDRDGRITVAELREAVPAlLGEPLAGPELDEMLREVDLNgdGTVDFDEFV 164
Cdd:cd16187    80 DSDRSGTVDPQELQKALTT-MGFRLSPQAVNSIAKRYSTN--GKITFDDYI 127

Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit CAPNS1 and CAPNS2; CAPNS1, also termed calpain small subunit 1 (CSS1), or calcium-activated neutral proteinase small subunit (CANP small subunit), or calcium-dependent protease small subunit (CDPS), or calpain regulatory subunit, is a common 28-kDa regulatory calpain subunit encoded by the calpain small 1 (Capns1, also known as Capn4) gene. It acts as a binding partner to form a heterodimer with the 80 kDa calpain large catalytic subunit and is required in maintaining the activity of calpain. CAPNS1 plays a significant role in tumor progression of human cancer, and functions as a potential therapeutic target in human hepatocellular carcinoma (HCC), nasopharyngeal carcinoma (NPC), glioma, and clear cell renal cell carcinoma (ccRCC). It may be involved in regulating migration and cell survival through binding to the SH3 domain of Ras GTPase-activating protein (RasGAP). It may also modulate Akt/FoxO3A signaling and apoptosis through PP2A. CAPNS1 contains an N-terminal glycine rich domain and a C-terminal PEF-hand domain. CAPNS2, also termed calpain small subunit 2 (CSS2), is a novel tissue-specific 30 kDa calpain small subunit that lacks two oligo-Gly stretches characteristic of the N-terminal Gly-rich domain of CAPNS1. CAPNS2 acts as a chaperone for the calpain large subunit, and appears to be the functional equivalent of CAPNS1. However, CAPNS2 binds the large subunit much more weakly than CAPNS1 and it does not undergo the autolytic conversion typical of CAPNS1.

Pssm-ID: 320063 [Multi-domain] Cd Length: 169 Bit Score: 37.41 E-value: 1.29e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  78 GRVDFEEFVELIGpklreetahmlGVRELRIAFREFDRDRDGRITVAELREAVPAllgeplAGPELDEMLREVDL----N 153
Cdd:cd16188    58 GKLGFEEFKYLWN-----------NIKKWQGIYKQFDTDRSGTIGSQELPGAFEA------AGFHLNEQLYQMIIrrysD 120

                          90
                  ....*....|....*.
gi 1824614785 154 GDGTVDFDEFVMMLSR 169
Cdd:cd16188   121 EDGNMDFDNFISCLVR 136

EF hand;

Pssm-ID: 433035 [Multi-domain] Cd Length: 25 Bit Score: 34.60 E-value: 1.30e-03

                          10        20
                  ....*....|....*....|....*
gi 1824614785  29 LQAAFEEFDTDRDGYISHRELGDCM 53
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRRLL 25

EF hand;

Pssm-ID: 433035 [Multi-domain] Cd Length: 25 Bit Score: 34.22 E-value: 1.97e-03

                          10        20
                  ....*....|....*....|...
gi 1824614785 106 LRIAFREFDRDRDGRITVAELRE 128
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRR 23

Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It displays a Ca2+-dependent translocation to granules and plasma membrane upon neutrophil activation, suggesting roles in granule-membrane fusion and degranulation of neutrophils. It may also play a role in the regulation of vesicle/granule exocytosis through the reversible binding of secretory vesicles and plasma membranes upon the presence of calcium. Moreover, GCA is involved in inflammation, as well as in the process of adhesion of neutrophils to fibronectin. It plays a key role in leukocyte-specific functions that are responsible for host defense, and affects the function of integrin receptors on immune cells through binding to L-plastin in the absence of calcium. Furthermore, GCA can strongly interact with sorcin to form a heterodimer, and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. GCA binds two Ca2+ ions through its EF1 and EF3 hands.

Pssm-ID: 320061 [Multi-domain] Cd Length: 165 Bit Score: 36.77 E-value: 2.30e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  40 RDGYISHRELGDCMRTLG----YMPTEMELLEVSqhIKM---RMGGRVDFEEFVELIGpklreetahmlGVRELRIAFRE 112
Cdd:cd16186    12 QDGEVDAEELQRCLTQSGingtYTPFSLETCRIM--IAMldrDHTGKMGFNEFKELWA-----------ALNAWKQNFMT 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1824614785 113 FDRDRDGRITVAELREAVpALLGEPLAGPELDEMLREVDLNgdGTVDFDEFV 164
Cdd:cd16186    79 VDQDRSGTVEPHELRQAI-GAMGYRLSPQTLTTIVKRYSKN--GRIYFDDYV 127

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), calpain-B (CalpB), and similar proteins; The family contains two calpains that have been found in Drosophila, CalpA and CalpB. CalpA, also termed calcium-activated neutral proteinase A (CANP A), or calpain-A catalytic subunit, is a Drosophila calpain homolog specifically expressed in a few neurons in the central nervous system, in scattered endocrine cells in the midgut, and in blood cells. CalpB, also termed calcium-activated neutral proteinase B (CANP B), contains calpain-B catalytic subunit 1 and calpain-B catalytic subunit 2. Both CalpA and CalpB are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. Besides, CalpA and CalpB display some distinguishing structural features that are not found in mammalian typical calpains. CalpA harbors a 76 amino acid long hydrophobic stretch inserted in domain IV, which may be involved in membrane attachment of this enzyme. CalpB has an unusually long N-terminal tail of 224 amino acids, which belongs to the class of intrinsically unstructured proteins (IUP) and may become ordered upon binding to target protein(s). Moreover, they do not need small regulatory subunits for their catalytic activity, and their proteolytic function is not regulated by an intrinsic inhibitor as the Drosophila genome contains neither regulatory subunit nor calpastatin orthologs. As a result, they may exist as a monomer or perhaps as a homo- or heterodimer together with a second large subunit. Furthermore, both CalpA and CalpB are dispensable for viability and fertility and do not share vital functions during Drosophila development. Phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol, and phosphatidic acid can stimulate the activity and the rate of activation of CalpA, but not CalpB. Calpain A modulates Toll responses by limited Cactus/IkappaB proteolysis. CalpB directly interacts with talin, an important component of the focal adhesion complex, and functions as an important modulator in border cell migration within egg chambers, which may act via the digestion of talin. CalpB can be phosphorylated by cAMP-dependent protein kinase (protein kinase A, PKA; EC 2.7.11.11) at Ser240 and Ser845, as well as by mitogen-activated protein kinase (ERK1 and ERK2; EC 2.7.11.24) at Thr747. The activation of the ERK pathway by extracellular signals results in the phosphorylation and activation of calpain B. In Schneider cells (S2), calpain B was mainly in the cytoplasm and upon a rise in Ca2+ the enzyme adhered to intracellular membranes.

Pssm-ID: 320071 [Multi-domain] Cd Length: 167 Bit Score: 36.80 E-value: 2.30e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  21 LGPEELDEL-------QAAFEEFDTDRDGYISHRELGDCMRTLGYmptemellEVSQHIK----MRMG---GRVDFEEFV 86
Cdd:cd16196    58 LGFEEFKKLwedlrswKRVFKLFDTDGSGSFSSFELRNALNSAGF--------RLSNATLnalvLRYSnkdGRISFDDFI 129

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1824614785  87 ELigpklreetahMLGVRELRIAFREFDRDRDGRIT 122
Cdd:cd16196   130 MC-----------AVKLKTMFEIFKEKDPRGGGRAT 154

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.

Pssm-ID: 320028 [Multi-domain] Cd Length: 268 Bit Score: 36.88 E-value: 2.85e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  27 DELQAAFEEFDTDRDGYISHRELgdcmRTLGYmptemellevsqhikmrmGGRVDFEEFVELIGPklrEETAHMLGVREL 106
Cdd:cd16230    73 DSVSAAWQTYDTDRDGRVGWEEL----RNATY------------------GHYEPGEEFHDVEDA---ETYKKMLARDER 127

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1824614785 107 RiaFREFDRDRDGRITVAELREAVPALLGEPLAGPELDEMLREVDLNGDGTVDFDEFVMML 167
Cdd:cd16230   128 R--FRVADQDGDSMATREELTAFLHPEEFPHMRDIVVAETLEDLDKNKDGYVQVEEYIADL 186

EF hand;

Pssm-ID: 433035 [Multi-domain] Cd Length: 25 Bit Score: 33.83 E-value: 3.10e-03

                          10        20
                  ....*....|....*....|....*
gi 1824614785 143 LDEMLREVDLNGDGTVDFDEFVMML 167
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRRLL 25

S-100A1: S-100A1 domain found in proteins similar to S100A1. S100A1 is a calcium-binding protein belonging to a large S100 vertebrate-specific protein family within the EF-hand superfamily of calcium-binding proteins. Note that the S-100 hierarchy, to which this S-100A1 group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. As is the case with many other members of S100 protein family, S100A1 is implicated in intracellular and extracellular regulatory activities, including interaction with myosin-associated twitchin kinase, actin-capping protein CapZ, sinapsin I, and tubulin. Structural data suggests that S100A1 proteins exist within cells as antiparallel homodimers, while heterodimers with S100A4 and S100B also has been reported. Upon binding calcium S100A1 changes conformation to expose a hydrophobic cleft which is the interaction site of S100A1 with its more that 20 known target proteins.

Pssm-ID: 240152 [Multi-domain] Cd Length: 92 Bit Score: 35.25 E-value: 3.69e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1824614785 120 RITVAELREAVPALLGEPLAGPE----LDEMLREVDLNGDGTVDFDEFVMMLS 168
Cdd:cd05025    27 KLSKKELKDLLQTELSDFLDAQKdadaVDKIMKELDENGDGEVDFQEFVVLVA 79

EF-hand domain pair;

Pssm-ID: 404678 [Multi-domain] Cd Length: 54 Bit Score: 33.83 E-value: 4.32e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1824614785  77 GGRVDFEEFVELigpkLREETAHMLGVRELRIAFREFDRDRDGRITVAE 125
Cdd:pfam13833   2 KGVITREELKRA----LALLGLKDLSEDEVDILFREFDTDGDGYISFDE 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.

Pssm-ID: 320021 [Multi-domain] Cd Length: 267 Bit Score: 36.27 E-value: 5.21e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  78 GRVDFEEFVELIGPKLReetahmlgvRELRIAFREFDRDRDGRITVAELREAVPALLGEpLAGPELDEMLREVDLNGDGT 157
Cdd:cd15899    18 GKEEAEEFDQLTPEESK---------RRLGVIVSKMDVDKDGFISAKELHSWILESFKR-HAMEESKEQFRAVDPDEDGH 87


                  ....*.
gi 1824614785 158 VDFDEF 163
Cdd:cd15899    88 VSWDEY 93

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed calcium-binding protein ERC-55, or E6-binding protein (E6BP), or TCBP-49, is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. It is associated with tumorigenesis, in particular with transformation of cells of the cervix induced by human papillomavirus (HPV), through binding to human papillomavirus (HPV) E6 oncogenic protein. It specifically interacts with vitamin D receptor among nuclear receptors. RCN2 contains an N-terminal signal sequence followed by six copies of the EF-hand Ca2+-binding motif, and a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).

Pssm-ID: 320022 [Multi-domain] Cd Length: 268 Bit Score: 36.26 E-value: 5.31e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  23 PEELDEL-----QAAFEEFDTDRDGYISHRE-LGDCMRTLGYMPTEMELLEVSQHIK----MRMGGRVDFEEFVELIGPK 92
Cdd:cd16224   152 PEEVDYMtefviQEALEEHDKDGDGFISLEEfLGDYRKDPTANEDPEWIIVEKDRFVndydKDNDGKLDPQELLPWVVPN 231

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1824614785  93 ----LREETAHMLgvrelriafREFDRDRDGRITVAELRE 128
Cdd:cd16224   232 nygiAQEEALHLI---------DEMDLNGDGRLSEEEILE 262

EF-hand domain;

Pssm-ID: 405361 Cd Length: 66 Bit Score: 33.94 E-value: 5.76e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785 110 FREFDRDRDGRITVAELREAVPALLGEPLAGPELDEMLREVDLNG-DGTVDFDEF--VMM 166
Cdd:pfam14658   4 FEVCDTQKTGRVPVSRLIDYLRAVTGQDPQESRLQTLARELDPDGeDALVDLDTFlrVMR 63

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.

Pssm-ID: 320076 [Multi-domain] Cd Length: 243 Bit Score: 35.58 E-value: 8.35e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824614785  33 FEEFDTDRDGYISHRELGDCMRTL--GYMPTEMELLEVSQHIKMRMGGRVDFE-EFVELIGPKLREETAHMLGVRELRI- 108
Cdd:cd16176     5 WHHYDNDGNGYIEGKELQSFIQELqqARKKAGLELSDQMKAFVDQYGQSTDGKiGIVELAQILPTEENFLLFFRQQLKSs 84

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1824614785 109 -----AFREFDRDRDGRITVAELREAVPALL---GEPLAGPELDE----MLREVDLNGDGTVDFDEFVMML 167
Cdd:cd16176    85 eefmqTWRKYDADHSGFIEADELKSFLKDLLkkaNKPFDESKLEEythtMLKMFDSNNDGKLGLTEMARLL 155

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.

Pssm-ID: 320057 [Multi-domain] Cd Length: 167 Bit Score: 35.28 E-value: 8.35e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1824614785  25 ELDELQAAFEEFDTDRDGYISHRELGDCMRTLGYmPTEMELLEVsqhIKMRMG---GRVDFEEFV 86
Cdd:cd16182    70 DLKKWQAIFKKFDTDRSGTLSSYELRKALESAGF-HLSNKVLQA---LVLRYAdstGRITFEDFV 130

Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1); CAPN1, also termed calpain-1 80-kDa catalytic subunit, or calpain-1 large subunit, or micromolar-calpain (muCANP), or calcium-activated neutral proteinase 1 (CANP 1), or cell proliferation-inducing gene 30 protein, is a ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine protease that contains 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 catalytic subunit CAPN1 in complex with a regulatory subunit encoded by CAPNS1 forms a mu-calpain heterodimer. CAPN1 plays a central role in postmortem proteolysis and meat tenderization processes, as well as in regulation of proliferation and survival of skeletal satellite cells. It also acts as a novel regulator in IgE-mediated mast cell activation and could serve as a potential therapeutic target for the management of allergic inflammation. Moreover, CAPN1 is involved in neutrophil motility and functions as a potential target for intervention in inflammatory disease. It also facilitates age-associated aortic wall calcification and fibrosis through the regulation of matrix metalloproteinase 2 activity in vascular smooth muscle cells, and thus plays a role in hypertension and atherosclerosis. The proteolytic cleavage of beta-amyloid precursor protein and tau protein by CAPN1 may be involved in plaque formation. Furthermore, CAPN1 is activated in the brains of individuals with Alzheimer's disease. It is involved in the maintenance of a proliferative neural stem cell pool. The activation and macrophage inflammation of CAPN1 in hypercholesterolemic nephropathy is promoted by nicotinic acetylcholine receptor alpha1 (nAChRalpha1). In addition, CAPN1 displays a functional role in hemostasis, as well as in sickle cell disease.

Pssm-ID: 320073 [Multi-domain] Cd Length: 169 Bit Score: 35.16 E-value: 9.54e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1824614785 103 VRELRIAFREFDRDRDGRITVAELREAVPAllgeplAGPELDEMLREVDL----NGDGTVDFDEFVMMLSR 169
Cdd:cd16198    72 IRNYLTIFRKFDLDKSGSMSAYEMRLALES------AGFKLNNRLHQVIVaryaDPNLAIDFDNFVCCLVR 136