NCBI Conserved Domain Search

calmodulin; Provisional

Pssm-ID: 185504 [Multi-domain] Cd Length: 149 Bit Score: 260.85 E-value: 4.46e-91

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767    1 MADQLTDEQISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKDT 80
Cdd:PTZ00184   1 MADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKDT 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15081767   81 DSEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFVKIMMAK 149
Cdd:PTZ00184  81 DSEEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMMMSK 149

centrin; Provisional

Pssm-ID: 185503 [Multi-domain] Cd Length: 158 Bit Score: 151.38 E-value: 1.01e-47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767    4 QLTDEQISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKDTDSE 83
Cdd:PTZ00183  10 GLTEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKLGERDPR 89

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15081767   84 EELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFVKIM 146
Cdd:PTZ00183  90 EEILKAFRLFDDDKTGKISLKNLKRVAKELGETITDEELQEMIDEADRNGDGEISEEEFYRIM 152

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 101.79 E-value: 1.84e-28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767   7 DEQISEFKEAFSLFDKDGDGCITTKELGTVMRslgqnpteAELQDMINEVDADGNGTIDFPEFLNLMAKKMKDTDsEEEL 86
Cdd:COG5126   1 DLQRRKLDRRFDLLDADGDGVLERDDFEALFR--------RLWATLFSEADTDGDGRISREEFVAGMESLFEATV-EPFA 71

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15081767  87 KEAFRVFDKDQNGFISAAELRHVMTNLGekLTDEEVEEMIREADVDGDGQINYEEFVKIMM 147
Cdd:COG5126  72 RAAFDLLDTDGDGKISADEFRRLLTALG--VSEEEADELFARLDTDGDGKISFEEFVAAVR 130

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: 83.75 E-value: 2.83e-22

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15081767  85 ELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFVKIMM 147
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 78.36 E-value: 3.06e-20

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15081767  12 EFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMA 74
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

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: 77.18 E-value: 1.39e-18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  12 EFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAE-LQDMINEVDADGNGTIDFPEFLNLMakkmkdtDSEEELKEAF 90
Cdd:cd16180   1 ELRRIFQAVDRDRSGRISAKELQRALSNGDWTPFSIEtVRLMINMFDRDRSGTINFDEFVGLW-------KYIQDWRRLF 73

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767  91 RVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFVKIMM 147
Cdd:cd16180  74 RRFDRDRSGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRRRGSISFDDFVEACV 130

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 69.97 E-value: 6.87e-17

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767    83 EEELKEAFRVFDKDQNGFISAAELRHVMTNL--GEKLTDEEVEEMIREADVDGDGQINYEEFVKIMM 147
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

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: 67.56 E-value: 1.58e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  62 GTIDFPEFLNLMAKKMKDTDSEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEK-----LTDEEVEEMIREADVDGDGQ 136
Cdd:cd16252  15 GSFNYSKFFEYMQKFQTSEQQEEAIRKAFQMLDKDKSGFIEWNEIKYILSTVPSSmpvapLSDEEAEAMIQAADTDGDGR 94


                ....*.
gi 15081767 137 INYEEF 142
Cdd:cd16252  95 IDFQEF 100

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: 66.02 E-value: 5.67e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  62 GTIDFPEFLNLMAKKMKdtdSEEELKEAFRVFDKDQNGFISAAELRHVMTNL---GEKLTDEEVEEMIREADVDGDGQIN 138
Cdd:cd16251  15 GSFNYKKFFEHVGLKQK---SEDQIKKVFQILDKDKSGFIEEEELKYILKGFsiaGRDLTDEETKALLAAGDTDGDGKIG 91


                ....*..
gi 15081767 139 YEEFVKI 145
Cdd:cd16251  92 VEEFATL 98

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: 67.66 E-value: 5.69e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  17 FSLFDKDGDGCITTKELGTVMrSLGQ----NPTEAELqdMINEVDADGNGTIDFPEFLNLMaKKMKDtdseeeLKEAFRV 92
Cdd:cd16183   6 FQRVDKDRSGQISATELQQAL-SNGTwtpfNPETVRL--MIGMFDRDNSGTINFQEFAALW-KYITD------WQNCFRS 75

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 15081767  93 FDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFV 143
Cdd:cd16183  76 FDRDNSGNIDKNELKQALTSFGYRLSDQFYDILVRKFDRQGRGTIAFDDFI 126

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: 62.30 E-value: 3.76e-13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  13 FKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKKMkdtdSEEELKEAFRV 92
Cdd:cd15898   2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLT----ERPELEPIFKK 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767  93 FDKDQNGFISAAELRHVMTN-LGEKLTDEEVEEMIREADVDG-DGQINYEEFVKIMM 147
Cdd:cd15898  78 YAGTNRDYMTLEEFIRFLREeQGENVSEEECEELIEKYEPEReNRQLSFEGFTNFLL 134

centrin; Provisional

Pssm-ID: 185503 [Multi-domain] Cd Length: 158 Bit Score: 62.78 E-value: 4.04e-13

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15081767    1 MADQLTDEQIsefKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKK 76
Cdd:PTZ00183  83 LGERDPREEI---LKAFRLFDDDKTGKISLKNLKRVAKELGETITDEELQEMIDEADRNGDGEISEEEFYRIMKKT 155

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: 63.91 E-value: 5.79e-13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  13 FKEAFSLFDKDGDGCITTKELGTVMRSL-----GQNPTEAELQDMINEV----DADGNGTIDFPEFLNLMAKK------- 76
Cdd:cd15902   1 FMEVWMHFDADGNGYIEGKELDSFLRELlkalnGKDKTDDEVAEKKKEFmekyDENEDGKIEIRELANILPTEenflllf 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  77 --MKDTDSEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEKL--------TDEEVEEMIREADVDGDGQINYEEFVKIM 146
Cdd:cd15902  81 rrEQPLISSVEFMKIWRKYDTDGSGFIEAKELKGFLKDLLLKNkkhvsppkLDEYTKLILKEFDANKDGKLELDEMAKLL 160

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: 61.46 E-value: 1.20e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  12 EFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKdtdseeeLKEAFR 91
Cdd:cd16185   1 ELRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRMFDRDGNGTIDFEEFAALHQFLSN-------MQNGFE 73

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 15081767  92 VFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFVKI 145
Cdd:cd16185  74 QRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFDPDRGGSLGFDDYIEL 127

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 60.19 E-value: 2.13e-12

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15081767   1 MADQLTDEQISEFKEAFSLFDKDGDGCITTKELGTVMRSLGqnPTEAELQDMINEVDADGNGTIDFPEFLNLMAK 75
Cdd:COG5126  59 MESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALG--VSEEEADELFARLDTDGDGKISFEEFVAAVRD 131

XopAW family type III secretion system calcium-binding effector;

Pssm-ID: 469301 [Multi-domain] Cd Length: 227 Bit Score: 60.85 E-value: 5.65e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767   14 KEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMA------KKMKDTDSEEELk 87
Cdd:NF041410  30 KQLFAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAPppppppDQAPSTELADDL- 108

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 15081767   88 eaFRVFDKDQNGFISAAELRHVMTNLGeklTDEEVEEMIREADVDGDGQINYEEF 142
Cdd:NF041410 109 --LSALDTDGDGSISSDELSAGLTSAG---SSADSSQLFSALDSDGDGSVSSDEL 158

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: 58.92 E-value: 1.14e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  25 DGCITTKELGTVMRSLG--QNPTEAELQD---MINEVDADGNGTIDFPEFLNLMAkkmkdtdSEEELKEAFRVFDKDQNG 99
Cdd:cd16181  13 DGQIDADELQRCLTQSGisGNYQPFSLETcrlMIAMLDRDHSGKMGFNEFKELWA-------ALNQWKTTFMQYDRDRSG 85

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 15081767 100 FISAAELRHVMTNLGEKLTDEEVEEMIREADVdgDGQINYEEFV 143
Cdd:cd16181  86 TVEPQELQQAIRSFGYNLSPQALNVIVKRYSK--NGRITFDDFV 127

XopAW family type III secretion system calcium-binding effector;

Pssm-ID: 469301 [Multi-domain] Cd Length: 227 Bit Score: 60.08 E-value: 1.29e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767    1 MADQLTDEQISEFKEAFSLFDKDGDGCITTKELGTVMRS----LGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKK 76
Cdd:NF041410  53 LSSKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAPPppppPDQAPSTELADDLLSALDTDGDGSISSDELSAGLTSA 132

                         90       100       110
                 ....*....|....*....|....*....|
gi 15081767   77 MKDTDSEeelkEAFRVFDKDQNGFISAAEL 106
Cdd:NF041410 133 GSSADSS----QLFSALDSDGDGSVSSDEL 158

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 55.72 E-value: 2.27e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15081767    10 ISEFKEAFSLFDKDGDGCITTKELGTVMRSL--GQNPTEAELQDMINEVDADGNGTIDFPEFLNLM 73
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66

centrin; Provisional

Pssm-ID: 185503 [Multi-domain] Cd Length: 158 Bit Score: 58.16 E-value: 2.41e-11

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15081767   81 DSEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFVKIMMAK 149
Cdd:PTZ00183  14 DQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKK 82

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, 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+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.

Pssm-ID: 320059 [Multi-domain] Cd Length: 165 Bit Score: 57.27 E-value: 5.23e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  17 FSLFDKDGDGCITTKEL-GTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKKmkdtdseEELKEAFRVFDK 95
Cdd:cd16184   6 FQAVDRDRSGKISAKELqQALVNGNWSHFNDETCRLMIGMFDKDKSGTIDIYEFQALWNYI-------QQWKQVFQQFDR 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 15081767  96 DQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFVKI 145
Cdd:cd16184  79 DRSGSIDENELHQALSQMGYRLSPQFVQFLVSKYDPRARRSLTLDQFIQV 128

EF-hand, calcium binding motif, found in beta-parvalbumin; Beta-parvalbumin, also termed Oncomodulin-1 (OM), is a small calcium-binding protein that is expressed in hepatomas, as well as in the blastocyst and the cytotrophoblasts of the placenta. It is also found to be expressed in the cochlear outer hair cells of the organ of Corti and frequently expressed in neoplasms. Mammalian beta-parvalbumin is secreted by activated macrophages and neutrophils. It may function as a tissue-specific Ca2+-dependent regulatory protein, and may also serve as a specialized cytosolic Ca2+ buffer. Beta-parvalbumin acts as a potent growth-promoting signal between the innate immune system and neurons in vivo. It has high and specific affinity for its receptor on retinal ganglion cells (RGC) and functions as the principal mediator of optic nerve regeneration. It exerts its effects in a cyclic adenosine monophosphate (cAMP)-dependent manner and can further elevate intracellular cAMP levels. Moreover, beta-parvalbumin is associated with efferent function and outer hair cell electromotility, and can identify different hair cell types in the mammalian inner ear. Beta-parvalbumin is 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+. The EF site displays a high-affinity for Ca2+/Mg2+, and the CD site is a low-affinity Ca2+-specific site. In addition, beta-parvalbumin is distinguished from other parvalbumins by its unusually low isoelectric point (pI = 3.1) and sequence eccentricities (e.g., Y57-L58-D59 instead of F57-I58-E59).

Pssm-ID: 319998 [Multi-domain] Cd Length: 101 Bit Score: 54.74 E-value: 1.16e-10

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  82 SEEELKEAFRVFDKDQNGFISAAELRHVMTNL---GEKLTDEEVEEMIREADVDGDGQINYEEFVKIMMA 148
Cdd:cd16255  32 SADDVKKVFEIIDQDKSGFIEEEELKLFLQNFssgARELTDAETKAFLKAGDSDGDGKIGVEEFQALVKA 101

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: 53.32 E-value: 1.82e-10

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15081767  48 ELQDMINEVDADGNGTIDFPEFLNLMaKKMKDTDSEEELKEAFRVFDKDQNGFISAAELRHVMT 111
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAAL-KSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

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: 53.12 E-value: 2.42e-10

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15081767  13 FKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINevdadgngTIDFPEFLNLMAKKMKDTD 81
Cdd:cd22949   5 FREAFILFDRDGDGELTMYEAVLAMRSCGIPLTNDEKDALPA--------SMNWDQFENWAKKKLAYSD 65

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: 56.68 E-value: 2.47e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  14 KEAFSLFDKDGDGCITTKELgTVMRSLGQNP--TEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKDTDSEEEL---KE 88
Cdd:cd15899 126 KKRFEAADQDGDLILTLEEF-LAFLHPEESPymLDFVIKETLEDLDKNGDGFISLEEFISDPYSADENEEEPEWVkveKE 204

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767  89 AFR-VFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFVK 144
Cdd:cd15899 205 RFVeLRDKDKDGKLDGEELLSWVDPSNQEIALEEAKHLIAESDENKDGKLSPEEILD 261

EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2+/Mg2+-binding protein expressed mainly in fast-twitch skeletal myofibrils, where it may act as a soluble relaxing factor facilitating the Ca2+-mediated relaxation phase. It is also expressed in rapidly firing neurons, particularly GABA-ergic neurons, and thus may confer protection against Ca2+ toxicity. The major role of alpha-parvalbumin is metal buffering and transport of Ca2+. It binds different metal cations, and exhibits very high affinity for Ca2+ and physiologically significant affinity for Mg2+. Alpha-parvalbumin is 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+. Both metal ion-binding sites in alpha-parvalbumin are high-affinity sites. Additionally, in contrast to beta-parvalbumin, alpha-parvalbumin is less acidic and has an additional residue in the C-terminal helix.

Pssm-ID: 319997 [Multi-domain] Cd Length: 101 Bit Score: 52.13 E-value: 1.58e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  62 GTIDFPEFLNLMAKKMKdtdSEEELKEAFRVFDKDQNGFISAAELRHVMTNL---GEKLTDEEVEEMIREADVDGDGQIN 138
Cdd:cd16254  15 DSFDYKKFFEMVGLKKK---SADDVKKVFHILDKDKSGFIEEDELKFVLKGFspdGRDLSDKETKALLAAGDKDGDGKIG 91


                ....*...
gi 15081767 139 YEEFVKIM 146
Cdd:cd16254  92 IDEFATLV 99

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: 52.82 E-value: 2.19e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  12 EFKEAFSLFDKDgDGCITTKELGTVMRSLGQNPTE-----AELQDMINEVDADGNGTIDFPEFLNLMaKKMKDtdseeeL 86
Cdd:cd15897   1 QLRNVFQAVAGD-DGEISATELQQALSNVGWTHFDlgfslETCRSMIAMMDRDHSGKLNFSEFKGLW-NYIKA------W 72

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767  87 KEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADvDGDGQINYEEFV 143
Cdd:cd15897  73 QEIFRTYDTDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYD-RGRGNIDFDDFI 128

Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and similar proteins; CAPN13, also termed calcium-activated neutral proteinase 13 (CANP 13), a 63.6 kDa calpain large subunit that exhibits a restricted tissue distribution with low levels of expression detected only in human testis and lung. In calpain family, CAPN13 is most closely related to calpain-14 (CAPN14). CAPN14, also termed calcium-activated neutral proteinase 14 (CANP 14), is a 76.7 kDa calpain large subunit that is most highly expressed in the oesophagus. Its expression and calpain activity can be induced by IL-13. Both CAPN13 and CAPN14 contain 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: 320070 [Multi-domain] Cd Length: 168 Bit Score: 52.21 E-value: 3.93e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  52 MINEVDADGNGTIDFPEFLNLMaKKMKdtdseeELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEM-IREAD 130
Cdd:cd16195  48 MVALMDLSVNGRLSLEEFSRLW-KKLR------KYKDIFQKADVSKSGFLSLSELRNAIQAAGIRVSDDLLNLMaLRYGD 120

                        90
                ....*....|....*..
gi 15081767 131 VdgDGQINYEEFVKIMM 147
Cdd:cd16195 121 S--SGRISFESFICLML 135

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: 52.70 E-value: 6.41e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  10 ISEFKEAFSLFDKDGDGCITTKELgtvmrSLGQNPTE------AELQDMINEVDADGNGTIDFPEFLNLMAKKMKDTDSE 83
Cdd:cd16227 121 LEDDKEMFEAADLNKDGKLDKTEF-----SAFQHPEEyphmhpVLIEQTLRDKDKDNDGFISFQEFLGDRAGHEDKEWLL 195

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  84 EELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFV 143
Cdd:cd16227 196 VEKDRFDEDYDKDGDGKLDGEEILSWLVPDNEEIAEEEVDHLFASADDDHDDRLSFDEIL 255

EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, MICU3, and similar proteins; This family includes mitochondrial calcium uptake protein MICU1 and its two additional paralogs, MICU2 and MICU3. MICU1 localizes to the inner mitochondrial membrane (IMM). It functions as a gatekeeper of the mitochondrial calcium uniporter (MCU) and regulates MCU-mediated mitochondrial Ca2+ uptake, which is essential for maintaining mitochondrial homoeostasis. MICU1 and MICU2 are physically associated within the uniporter complex and are co-expressed across all tissues. They may play non-redundant roles in the regulation of the mitochondrial calcium uniporter. At present, the precise molecular function of MICU2 and MICU3 remain unclear. MICU2 may play possible roles in Ca2+ sensing and regulation of MCU, calcium buffering with a secondary impact on transport or assembly and stabilization of MCU. MICU3 likely has a role in mitochondrial calcium handling. All members in this family contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.

Pssm-ID: 320080 [Multi-domain] Cd Length: 152 Bit Score: 50.69 E-value: 1.07e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  13 FKEAFSLFDKDGDGCITTKELGTVMR------SLGQNPTEAELQDMINEVD----------ADGNGTIDFPEFLNLMAKK 76
Cdd:cd15900   2 FEIAFKMFDLDGDGELDKEEFNKVQSiirsqtSVGQRHRDHTNGESTKLGMnstlaryffgKDGKQKLSIEKFLEFQENL 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15081767  77 MKDTDseeELKEAFRvFDKDQNGFISAAELRHVM-TNLGEKLTDEEVEEMIREADVDGDGQINYEEFVKIM 146
Cdd:cd15900  82 QEEID---DVDTALT-FYHLAGASIDRKTFKRAAkVVAGVELSDHVVDVVFTIFDEDGDGILSHKEFISVM 148

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: 51.07 E-value: 1.07e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  52 MINEVDADGNGTIDFPEFLNLMAKKmkdtdseEELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLtDEEVEEMIREADV 131
Cdd:cd16182  47 LIALMDTNGSGRLDLEEFKTLWSDL-------KKWQAIFKKFDTDRSGTLSSYELRKALESAGFHL-SNKVLQALVLRYA 118

                        90
                ....*....|..
gi 15081767 132 DGDGQINYEEFV 143
Cdd:cd16182 119 DSTGRITFEDFV 130

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: 51.97 E-value: 1.33e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  12 EFKEAFSLFDKDGDGCITTKELGTVMRSL--------GQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKK------- 76
Cdd:cd15902  91 EFMKIWRKYDTDGSGFIEAKELKGFLKDLllknkkhvSPPKLDEYTKLILKEFDANKDGKLELDEMAKLLPVQenfllkf 170

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  77 ---MKDTDSEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEK---LTDEEVEEMIREA-----DVDGDGQINYEEFVKI 145
Cdd:cd15902 171 qilGAMDLTKEDFEKVFEHYDKDNNGVIEGNELDALLKDLLEKnkaDIDKPDLENFRDAilracDKNKDGKIQKTELALF 250


                ....
gi 15081767 146 MMAK 149
Cdd:cd15902 251 LSAK 254

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: 49.45 E-value: 3.75e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  10 ISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKDTDseeelkeA 89
Cdd:cd16180  66 IQDWRRLFRRFDRDRSGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRRRGSISFDDFVEACVTLKRLTD-------A 138

                        90
                ....*....|..
gi 15081767  90 FRVFDKDQNGFI 101
Cdd:cd16180 139 FRKYDTNRTGYA 150

XopAW family type III secretion system calcium-binding effector;

Pssm-ID: 469301 [Multi-domain] Cd Length: 227 Bit Score: 50.06 E-value: 5.26e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767   39 SLGQNPTEAELQ-DMINEVDADGNGTIDFPEFLNLMAKKmKDTDSEEELKEAFRVFDKDQNGFISAAELRHVMTN----L 113
Cdd:NF041410  18 SSTSSARSQQFQkQLFAKLDSDGDGSVSQDELSSALSSK-SDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAPPppppP 96

                         90       100
                 ....*....|....*....|....*....
gi 15081767  114 GEKLTDEEVEEMIREADVDGDGQINYEEF 142
Cdd:NF041410  97 DQAPSTELADDLLSALDTDGDGSISSDEL 125

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: 48.40 E-value: 1.19e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  10 ISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLN--LMAKKmkdtdseeeLK 87
Cdd:cd16183  66 ITDWQNCFRSFDRDNSGNIDKNELKQALTSFGYRLSDQFYDILVRKFDRQGRGTIAFDDFIQccVVLQT---------LT 136

                        90
                ....*....|....
gi 15081767  88 EAFRVFDKDQNGFI 101
Cdd:cd16183 137 DSFRRYDTDQDGWI 150

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: 48.17 E-value: 2.37e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  13 FKEAFSLFDKDGDGCITTKELGTVMRSLGQ------NPTEAELQDM----INEVDADGNGTIDFPEFLN----------L 72
Cdd:cd16178   1 FAEIWQHFDADESGYIEGKELDNFFKDLLKklgtkdTISADEVQDVkecfMSAYDVTGDGRIQIQELANiilpddenflL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  73 MAKKMKDTDSEEELKEAFRVFDKDQNGFISAAELRHVMTNL----GEKLTDEEVEE----MIREADVDGDGQINYEEFVK 144
Cdd:cd16178  81 FFRREEPLDSSVEFMRIWRKYDADSSGYISAAELKNFLRDLflqhKKVITEDKLDEytdtMMKIFDKNKDGRLDLNDMAR 160


                ..
gi 15081767 145 IM 146
Cdd:cd16178 161 IL 162

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

Pssm-ID: 197477 [Multi-domain] Cd Length: 96 Bit Score: 45.73 E-value: 2.76e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767     82 SEEELK--EAFRVFDKDQNGFISAAELRHVMTNLGekLTDEEVEEMIREADVDGDGQINYEEFVKIM 146
Cdd:smart00027   6 PEDKAKyeQIFRSLDKNQDGTVTGAQAKPILLKSG--LPQTLLAKIWNLADIDNDGELDKDEFALAM 70

EF-hand domain pair;

Pssm-ID: 404678 [Multi-domain] Cd Length: 54 Bit Score: 44.23 E-value: 4.68e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 15081767    97 QNGFISAAELRHVMTNLGEK-LTDEEVEEMIREADVDGDGQINYEEFVKIM 146
Cdd:pfam13833   1 EKGVITREELKRALALLGLKdLSEDEVDILFREFDTDGDGYISFDEFCVLL 51

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: 44.13 E-value: 7.51e-07

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767  87 KEAFRVFDKDQNGFISAAELRHVMTNLGekLTDEEVEEMIREADVDGDGQINYEEFV 143
Cdd:cd00052   2 DQIFRSLDPDGDGLISGDEARPFLGKSG--LPRSVLAQIWDLADTDKDGKLDKEEFA 56

EF-hand, calcium binding motif, found in parvalbumins; 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: 319996 [Multi-domain] Cd Length: 101 Bit Score: 44.86 E-value: 7.53e-07

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15081767  82 SEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEK---LTDEEVEEMIREADVDGDGQINYEEF 142
Cdd:cd16253  32 SPADIKKVFNILDQDKSGFIEEEELKLFLKNFSDGarvLSDKETKNFLAAGDSDGDGKIGVDEF 95

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: 46.79 E-value: 7.75e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  13 FKEAFSLFDKDGDGCITTKELGTVMRSL-------GQNPTEAELQDMINEV----DADGNGTIDFPEFLNLMAKK----- 76
Cdd:cd16177   1 FLEIWKHFDADGNGYIEGKELENFFRELerarrgaGVDSKSANFGEKMKEFmqkyDKNADGRIEMAELAQILPTEenfll 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  77 --MKDTDSEEELKEAFRVFDKDQNGFISAAELRHVMTNL--------GEKLTDEEVEEMIREADVDGDGQINYEEFVKIM 146
Cdd:cd16177  81 cfRQHVGSSSEFMEAWRKYDTDRSGYIEANELKGFLSDLlkkanrpyDEKKLQEYTQTILRMFDLNGDGKLGLSEMARLL 160

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: 46.37 E-value: 9.38e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  13 FKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEA------ELQDMINEVDADGNGTIDFPE----------FLNLMAKK 76
Cdd:cd16176   1 FLEIWHHYDNDGNGYIEGKELQSFIQELQQARKKAglelsdQMKAFVDQYGQSTDGKIGIVElaqilpteenFLLFFRQQ 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15081767  77 MKdtdSEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLT--------DEEVEEMIREADVDGDGQINYEEFVKIM 146
Cdd:cd16176  81 LK---SSEEFMQTWRKYDADHSGFIEADELKSFLKDLLKKANkpfdesklEEYTHTMLKMFDSNNDGKLGLTEMARLL 155

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.

Pssm-ID: 320024 [Multi-domain] Cd Length: 264 Bit Score: 46.04 E-value: 1.36e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767   3 DQLTDEQISE-FKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKDTD 81
Cdd:cd16226  26 DQLTPEESKErLGIIVDKIDKNGDGFVTEEELKDWIKYVQKKYIREDVDRQWKEYDPNKDGKLSWEEYKKATYGFLDDEE 105

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  82 SEEELKEA-----------FRVFDKDQNGFISAAELRHVM-----TNLGEKLTDEEVEEMireaDVDGDGQINYEEFVKI 145
Cdd:cd16226 106 EDDDLHESykkmirrderrWKAADQDGDGKLTKEEFTAFLhpeefPHMRDIVVQETLEDI----DKNKDGFISLEEYIGD 181


                .
gi 15081767 146 M 146
Cdd:cd16226 182 M 182

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain 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 C-terminal C2 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. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.

Pssm-ID: 320032 [Multi-domain] Cd Length: 140 Bit Score: 44.14 E-value: 2.80e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15081767  86 LKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFVK 144
Cdd:cd16202   2 LKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVQ 60

EF-hand domain;

Pssm-ID: 463869 [Multi-domain] Cd Length: 30 Bit Score: 41.78 E-value: 2.88e-06

                          10        20        30
                  ....*....|....*....|....*....|
gi 15081767    85 ELKEAFRVFDKDQNGFISAAELRHVMTNLG 114
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.

Pssm-ID: 320024 [Multi-domain] Cd Length: 264 Bit Score: 45.27 E-value: 2.90e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  14 KEAFSLFDKDGDGCITTKELGTVMrslgqNPTEAE------LQDMINEVDADGNGTIDFPEFLNLMAKK---MKDTDSEE 84
Cdd:cd16226 122 ERRWKAADQDGDGKLTKEEFTAFL-----HPEEFPhmrdivVQETLEDIDKNKDGFISLEEYIGDMYRDddeEEDPDWVK 196

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15081767  85 ELKEAFRVF-DKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEE 141
Cdd:cd16226 197 SEREQFKEFrDKNKDGKMDREEVKDWILPEDYDHAEAEAKHLIYEADDDKDGKLTKEE 254

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: 44.11 E-value: 3.70e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  52 MINEVDADGNGTIDFPEFLNLMakkmkdtdseEEL---KEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIRE 128
Cdd:cd16196  46 MVAMMDVDRSGKLGFEEFKKLW----------EDLrswKRVFKLFDTDGSGSFSSFELRNALNSAGFRLSNATLNALVLR 115

                        90
                ....*....|....*....
gi 15081767 129 AdVDGDGQINYEEFVKIMM 147
Cdd:cd16196 116 Y-SNKDGRISFDDFIMCAV 133

EF-hand domain;

Pssm-ID: 463869 [Multi-domain] Cd Length: 30 Bit Score: 41.01 E-value: 4.66e-06

                          10        20        30
                  ....*....|....*....|....*....|
gi 15081767    12 EFKEAFSLFDKDGDGCITTKELGTVMRSLG 41
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30

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: 41.57 E-value: 6.27e-06

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15081767  82 SEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMireadvdgDGQINYEEFVKIMMAK 149
Cdd:cd22949   1 MEEKFREAFILFDRDGDGELTMYEAVLAMRSCGIPLTNDEKDAL--------PASMNWDQFENWAKKK 60

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.

Pssm-ID: 197492 [Multi-domain] Cd Length: 29 Bit Score: 40.44 E-value: 8.45e-06

                           10        20
                   ....*....|....*....|....*....
gi 15081767    121 EVEEMIREADVDGDGQINYEEFVKIMMAK 149
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

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: 42.80 E-value: 1.20e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  10 ISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEaELQDMINEVDADGNGTIDFPEFLNLMAKKmkdtdseEELKEA 89
Cdd:cd15897  69 IKAWQEIFRTYDTDGSGTIDSNELRQALSGAGYRLSE-QTYDIIIRRYDRGRGNIDFDDFIQCCVRL-------QRLTDA 140

                        90
                ....*....|..
gi 15081767  90 FRVFDKDQNGFI 101
Cdd:cd15897 141 FRRYDKDQDGQI 152

EF-hand domain pair;

Pssm-ID: 404678 [Multi-domain] Cd Length: 54 Bit Score: 40.38 E-value: 1.21e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 15081767    24 GDGCITTKELGTVMRSLG-QNPTEAELQDMINEVDADGNGTIDFPEFLNLMAK 75
Cdd:pfam13833   1 EKGVITREELKRALALLGlKDLSEDEVDILFREFDTDGDGYISFDEFCVLLER 53

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, 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+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.

Pssm-ID: 320059 [Multi-domain] Cd Length: 165 Bit Score: 42.64 E-value: 1.33e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  10 ISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNL--MAKKMKDtdseeelk 87
Cdd:cd16184  66 IQQWKQVFQQFDRDRSGSIDENELHQALSQMGYRLSPQFVQFLVSKYDPRARRSLTLDQFIQVcvQLQSLTD-------- 137

                        90
                ....*....|....
gi 15081767  88 eAFRVFDKDQNGFI 101
Cdd:cd16184 138 -AFRQRDTQMTGTI 150

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: 39.31 E-value: 1.71e-05

                          10        20
                  ....*....|....*....|....*...
gi 15081767   121 EVEEMIREADVDGDGQINYEEFVKIMMA 148
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKK 28

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: 41.36 E-value: 1.77e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767   4 QLTDEQISEFKEAFSLFDKDGDGCITTKE----LGTVMRSLGQNP-TEAELQDMINEVDADGNGTIDFPEFLNLMAK 75
Cdd:cd16252  30 QTSEQQEEAIRKAFQMLDKDKSGFIEWNEikyiLSTVPSSMPVAPlSDEEAEAMIQAADTDGDGRIDFQEFSDMVKK 106

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: 41.88 E-value: 1.79e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  11 SEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPteaELQDMINEVDADGNGTIDFPEFLNLMAKKMKDTDSEEELKEAF 90
Cdd:cd15898  36 KELKKLFKEVDTNGDGTLTFDEFEELYKSLTERP---ELEPIFKKYAGTNRDYMTLEEFIRFLREEQGENVSEEECEELI 112

                        90
                ....*....|...
gi 15081767  91 RVFDKD-QNGFIS 102
Cdd:cd15898 113 EKYEPErENRQLS 125

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: 42.80 E-value: 1.97e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  45 TEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKDTDSEE-ELKEAFRV---FDKDQNGFISAAE-LRHVMTNlGEKLTD 119
Cdd:cd16224 159 TEFVIQEALEEHDKDGDGFISLEEFLGDYRKDPTANEDPEwIIVEKDRFvndYDKDNDGKLDPQElLPWVVPN-NYGIAQ 237

                        90       100
                ....*....|....*....|....*
gi 15081767 120 EEVEEMIREADVDGDGQINYEEFVK 144
Cdd:cd16224 238 EEALHLIDEMDLNGDGRLSEEEILE 262

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: 39.90 E-value: 2.75e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15081767  13 FKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTeaELQDMINEVDADGNGTIDFPEFLNLM 73
Cdd:cd00052   1 YDQIFRSLDPDGDGLISGDEARPFLGKSGLPRS--VLAQIWDLADTDKDGKLDKEEFAIAM 59

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: 38.90 E-value: 3.28e-05

                           10        20
                   ....*....|....*....|....*....
gi 15081767     12 EFKEAFSLFDKDGDGCITTKELGTVMRSL 40
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

phosphatidylserine decarboxylase

Pssm-ID: 215520 [Multi-domain] Cd Length: 644 Bit Score: 42.15 E-value: 3.78e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15081767   83 EEELKEAFRVF---DKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEE 141
Cdd:PLN02964 175 ETERSFARRILaivDYDEDGQLSFSEFSDLIKAFGNLVAANKKEELFKAADLNGDGVVTIDE 236

EF-hand domain;

Pssm-ID: 405361 Cd Length: 66 Bit Score: 39.33 E-value: 4.55e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 15081767    17 FSLFDKDGDGCITTKELGTVMRSLGQN-PTEAELQDMINEVDADG-NGTIDFPEFLNLM 73
Cdd:pfam14658   4 FEVCDTQKTGRVPVSRLIDYLRAVTGQdPQESRLQTLARELDPDGeDALVDLDTFLRVM 62

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: 38.13 E-value: 6.33e-05

                           10        20
                   ....*....|....*....|....*....
gi 15081767     85 ELKEAFRVFDKDQNGFISAAELRHVMTNL 113
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

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: 40.66 E-value: 6.64e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  52 MINEVDADGNGTIDFPEFLNLMAkkmkdtdSEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADV 131
Cdd:cd16187  45 MISMLDRDMSGTMGFNEFKELWA-------VLNGWRQHFISFDSDRSGTVDPQELQKALTTMGFRLSPQAVNSIAKRYST 117

                        90
                ....*....|..
gi 15081767 132 dgDGQINYEEFV 143
Cdd:cd16187 118 --NGKITFDDYI 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: 37.77 E-value: 7.75e-05

                          10        20
                  ....*....|....*....|....*....
gi 15081767    85 ELKEAFRVFDKDQNGFISAAELRHVMTNL 113
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29

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: 40.89 E-value: 8.39e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767   3 DQLT-DEQISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKDTD 81
Cdd:cd15899  26 DQLTpEESKRRLGVIVSKMDVDKDGFISAKELHSWILESFKRHAMEESKEQFRAVDPDEDGHVSWDEYKNDTYGSVGDDE 105

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  82 SEE---------------ELKEAFRVFDKDQNGFISAAEL---RHVMTNLGekLTDEEVEEMIREADVDGDGQINYEEFV 143
Cdd:cd15899 106 ENVadnikedeeykklllKDKKRFEAADQDGDLILTLEEFlafLHPEESPY--MLDFVIKETLEDLDKNGDGFISLEEFI 183


                ...
gi 15081767 144 KIM 146
Cdd:cd15899 184 SDP 186

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: 37.38 E-value: 1.04e-04

                          10        20
                  ....*....|....*....|....*....
gi 15081767    12 EFKEAFSLFDKDGDGCITTKELGTVMRSL 40
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29

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: 36.97 E-value: 1.32e-04

                           10        20
                   ....*....|....*....|....*....
gi 15081767     48 ELQDMINEVDADGNGTIDFPEFLNLMAKK 76
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

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: 1.52e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767  11 SEFKEAFSLFDKDGDGCITTKELGTVMRSL---GQNPTEAELQDMINEVDADGNGTIDFPEFLNLMA 74
Cdd:cd16251  34 DQIKKVFQILDKDKSGFIEEEELKYILKGFsiaGRDLTDEETKALLAAGDTDGDGKIGVEEFATLVA 100

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: 40.09 E-value: 1.82e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  13 FKEAFSLFDKDGDGCITTKELGTVMRSL----------GQNPTEAELQDMINEV----DADGNGTIDFPE---------- 68
Cdd:cd16179   1 FMDVWNHYDTDGNGYIEGTELDGFLREFvssvnpedvgPEVVSETALEELKEEFmeayDENQDGRIDIRElaqllpteen 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  69 FLNLMAKKMKdTDSEEELKEAFRVFDKDQNGFISAAELRHVMTN-LGEKLTDEEVEE---------MIREADVDGDGQIN 138
Cdd:cd16179  81 FLLLFRRDNP-LDSSVEFMKVWREYDKDNSGYIEADELKNFLKHlLKEAKRDNDVSEdklieytdtILQLFDRNKDGKLQ 159

                       170
                ....*....|.
gi 15081767 139 YEEFVKIMMAK 149
Cdd:cd16179 160 LSEMARLLPVK 170

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: 38.89 E-value: 2.58e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  10 ISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDAdgNGTIDFPEFLNLmAKKMKdtdseeELKEA 89
Cdd:cd16181  69 LNQWKTTFMQYDRDRSGTVEPQELQQAIRSFGYNLSPQALNVIVKRYSK--NGRITFDDFVAC-AVRLR------ALTDR 139

                        90
                ....*....|
gi 15081767  90 FRVFDKDQNG 99
Cdd:cd16181 140 FRRRDTQQNG 149

Penta-EF hand, calcium binding motifs, found in calpain-8 (CAPN8); CAPN8, also termed new calpain 2 (nCL-2), or stomach-specific M-type calpain, is a calpain large subunit predominantly expressed in the stomach. It appears to be involved in membrane trafficking in the gastric surface mucus cells (pit cells), via its location at the Golgi and interaction with the beta-subunit of coatomer complex (beta-COP) of vesicles derived from the Golgi. Moreover, CAPN8, together with CAPN9, forms an active protease complex, G-calpain, in which both proteins are essential for stability and activity. The G-Calpain has been implicated in gastric mucosal defense. CAPN8 exists as both a monomer and homo-oligomer, but not as a heterodimer with the conventional calpain regulatory subunit (30K). The monomer and homodimer forms predominate. CAPN8 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: 320066 [Multi-domain] Cd Length: 168 Bit Score: 38.99 E-value: 2.89e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  12 EFKeafSLFDK-DGDGC-ITTKELGTVM-RSLGQNP-------TEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKdtd 81
Cdd:cd16191   1 EFK---NIFQKlAGKKCeVTANELQTILnRVLSKRKdiksdgfTINTCREMISLLDTDGTGTLGLVEFRILWMKIQK--- 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15081767  82 seeeLKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDeEVEEMIREADVDGDGQINYEEFVKIMM 147
Cdd:cd16191  75 ----YLAIYKKVDSDRSGTIDAHEMRNALQEAGFTLNN-KIQQSIVQRYASNKLTINFDGFIACMI 135

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1, or phospholipase C-eta-1 (PLC-eta-1), or phospholipase C-like protein 3 (PLC-L3), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the zona incerta and in the spinal cord. PI-PLC-eta1 may perform a fundamental role in the brain. It may also act in synergy with other PLC subtypes. For instance, it is activated via intracellular Ca2+ mobilization and then plays a role in the amplification of GPCR (G-protein-coupled receptor)-mediated PLC-beta signals. In addition, its activity can be stimulated by ionomycin. PI-PLC-eta1 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.

Pssm-ID: 320050 [Multi-domain] Cd Length: 141 Bit Score: 38.47 E-value: 3.24e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767  14 KEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGN-GTIDFPEF 69
Cdd:cd16220   3 KQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENqGTLTFEEF 59

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain 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 C-terminal C2 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. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.

Pssm-ID: 320032 [Multi-domain] Cd Length: 140 Bit Score: 38.36 E-value: 3.30e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  14 KEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKdtdsEEELKEAFRVF 93
Cdd:cd16202   3 KDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVQFYNRLTK----RPEIEELFKKY 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15081767  94 DKDQnGFISAAELRHVMTNLGEKL--TDEEVEEMIREADVDGDGQIN----YEEFVKIMMAK 149
Cdd:cd16202  79 SGDD-EALTVEELRRFLQEEQKVKdvTLEWAEQLIETYEPSEDLKAQglmsLDGFTLFLLSP 139

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: 39.19 E-value: 3.65e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  17 FSLFDKDGDGCITTKELGTVMrslgqNPTEAE------LQDMINEVDADGNGTIDFPEFLnlmAKKMKDTDSEEEL---- 86
Cdd:cd16230 129 FRVADQDGDSMATREELTAFL-----HPEEFPhmrdivVAETLEDLDKNKDGYVQVEEYI---ADLYSGEPGEEEPawvq 200

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  87 --KEAFRVF-DKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFV 143
Cdd:cd16230 201 teRQQFRQFrDLNKDGRLDGSEVGHWVLPPSQDQPLVEANHLLHESDTDKDGRLSKAEIL 260

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.

Pssm-ID: 320051 [Multi-domain] Cd Length: 141 Bit Score: 38.37 E-value: 4.01e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767  14 KEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGN-GTIDFPEF 69
Cdd:cd16221   3 KQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNqGTLGFEEF 59

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: 38.63 E-value: 4.09e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  52 MINEVDADGNGTIDFPEFlNLMAKKMKDtdseeeLKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDeEVEEMIREADV 131
Cdd:cd16198  48 MVNLMDKDGNGKLGLVEF-NILWNKIRN------YLTIFRKFDLDKSGSMSAYEMRLALESAGFKLNN-RLHQVIVARYA 119

                        90
                ....*....|..
gi 15081767 132 DGDGQINYEEFV 143
Cdd:cd16198 120 DPNLAIDFDNFV 131

EF-hand, calcium binding motif, found in calcium uptake protein 3, mitochondrial (MICU3) and similar proteins; MICU3, also termed EF-hand domain-containing family member A2 (EFHA2), is a paralog of MICU1 and notably found in the central nervous system (CNS) and skeletal muscle. At present, the precise molecular function of MICU3 remains unclear. It likely has a role in mitochondrial calcium handling. MICU3 contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.

Pssm-ID: 320083 [Multi-domain] Cd Length: 128 Bit Score: 37.88 E-value: 4.16e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  13 FKEAFSLFDKDGDGCITTKE---LGTVMRSLgqnpteaelqdMINEVDADGNGTIDFPEFLNLMAKKMKDTDseeELKEA 89
Cdd:cd16175   2 FRIAFNMFDTDGNEMVDKKEflvLQEIFRTL-----------LVHFFGKKGKAELNFEDFYRFMDNLQTEVE---DFTIA 67

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767  90 FRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFVKIM 146
Cdd:cd16175  68 MRMYTFADRSISQDEFARAVKVCTGLKLSPHLVNTVFKIFDVDGDGQLSYKEFIGIM 124

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1, or phospholipase C-eta-1 (PLC-eta-1), or phospholipase C-like protein 3 (PLC-L3), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the zona incerta and in the spinal cord. PI-PLC-eta1 may perform a fundamental role in the brain. It may also act in synergy with other PLC subtypes. For instance, it is activated via intracellular Ca2+ mobilization and then plays a role in the amplification of GPCR (G-protein-coupled receptor)-mediated PLC-beta signals. In addition, its activity can be stimulated by ionomycin. PI-PLC-eta1 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.

Pssm-ID: 320050 [Multi-domain] Cd Length: 141 Bit Score: 38.08 E-value: 5.34e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15081767  86 LKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGD-GQINYEEF 142
Cdd:cd16220   2 VKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENqGTLTFEEF 59

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: 38.54 E-value: 5.57e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  12 EFKEAFSLFDKDGDGCITTKELGTVMRSLGQN------PTEAELQD----MINEVDADGNGTIDFPEFLNLM-------- 73
Cdd:cd16179  96 EFMKVWREYDKDNSGYIEADELKNFLKHLLKEakrdndVSEDKLIEytdtILQLFDRNKDGKLQLSEMARLLpvkenflc 175

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  74 ------AKKMKDTDSEEelkeAFRVFDKDQNGFISAAELRHVMTNL----GEKLTDEEVEEM----IREADVDGDGQINY 139
Cdd:cd16179 176 rpifkgAGKLTREDIDR----VFALYDRDNNGTIENEELTGFLKDLlelvQEDYDEQDLEEFkeiiLRGWDFNNDGKISR 251


                ....*....
gi 15081767 140 EEFVKIMMA 148
Cdd:cd16179 252 KELTMLLLQ 260

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: 35.45 E-value: 5.66e-04

                          10        20
                  ....*....|....*....|....*...
gi 15081767    48 ELQDMINEVDADGNGTIDFPEFLNLMAK 75
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKK 28

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

Pssm-ID: 197477 [Multi-domain] Cd Length: 96 Bit Score: 36.87 E-value: 6.53e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15081767      5 LTDEQISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEaeLQDMINEVDADGNGTIDFPEF 69
Cdd:smart00027   4 ISPEDKAKYEQIFRSLDKNQDGTVTGAQAKPILLKSGLPQTL--LAKIWNLADIDNDGELDKDEF 66

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes represent a class of neuron-specific metazoan PI-PLCs that are most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. They are phosphatidylinositol 4,5-bisphosphate-hydrolyzing enzymes that are more sensitive to Ca2+ than other PI-PLC isozymes. They function as calcium sensors activated by small increases in intracellular calcium concentrations. They are also activated through G-protein-coupled receptor (GPCR) stimulation, and further mediate GPCR signalling pathways. PI-PLC-eta isozymes contain an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases. There are two PI-PLC-eta isozymes (1-2). Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.

Pssm-ID: 320035 [Multi-domain] Cd Length: 141 Bit Score: 37.75 E-value: 6.87e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15081767  86 LKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVD-GDGQINYEEFV 143
Cdd:cd16205   2 LKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDdNQGTLDFEEFC 60

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.

Pssm-ID: 320051 [Multi-domain] Cd Length: 141 Bit Score: 37.60 E-value: 7.60e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15081767  86 LKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGD-GQINYEEF 142
Cdd:cd16221   2 LKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNqGTLGFEEF 59

Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1), m-type calpain (CAPN2), and similar proteins; The family includes mu-type calpain (CAPN1) and m-type calpain (CAPN2), both of which are ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine proteases that 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 catalytic subunit CAPN1 or CAPN2 in complex with a regulatory subunit encoded by CAPNS1 forms a mu- or m-calpain heterodimer, respectively.

Pssm-ID: 320064 [Multi-domain] Cd Length: 168 Bit Score: 37.72 E-value: 7.91e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  50 QDMINEVDADGNGTIDFPEFLNLMAKKMKdtdseeeLKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDeEVEEMIREA 129
Cdd:cd16189  46 RNMVNLLDKDGSGKLGLVEFQILWTKIQK-------YLKIYKKFDTDGSGTMSSYEMRLALEEAGFKLNN-QLHQVLVAR 117

                        90
                ....*....|....*...
gi 15081767 130 DVDGDGQINYEEFVKIMM 147
Cdd:cd16189 118 YADQELTIDFDNFVRCLV 135

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

Pssm-ID: 320026 [Multi-domain] Cd Length: 263 Bit Score: 38.00 E-value: 8.32e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  17 FSLFDKDGDGCITTKELGTVMrslgqNPTEAE------LQDMINEVDADGNGTIDFPEFLNLMAKKMKDTDSEEELK--- 87
Cdd:cd16228 124 FKMADKDGDLRATKEEFTAFL-----HPEEYDymkdivVLETMEDIDKNGDGFIDLEEYIGDMYSQDGDADEPEWVKter 198

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15081767  88 EAFRVF-DKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFV 143
Cdd:cd16228 199 EQFTEFrDKNKDGKMDKEETKDWILPSDYDHAEAEARHLVYESDQNKDGKLTKEEIV 255

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: 36.31 E-value: 8.73e-04

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 15081767  30 TKELGTVMRSLGQNPTeaeLQDMINEVDADGNGTIDFPEFLNLMAK 75
Cdd:cd00213  37 ETELPNFLKNQKDPEA---VDKIMKDLDVNKDGKVDFQEFLVLIGK 79

Calcium-activated neutral; CAPN3, also termed calcium-activated neutral proteinase 3 (CANP 3), or calpain L3, or calpain p94, or muscle-specific calcium-activated neutral protease 3, or new calpain 1 (nCL-1), is a calpain large subunit that is mainly expressed in skeletal muscle, or lens. The skeletal muscle-specific CAPN3 are pathologically associated with limb girdle muscular dystrophy type 2A (LGMD2A). Its autolytic activity can be positively regulated by calmodulin (CaM), a known transducer of the calcium signal. CAPN3 is also involved in human melanoma tumorigenesis and progression. It impairs cell proliferation and stimulates oxidative stress-mediated cell death in melanoma cells. Moreover, it plays an important role in sarcomere remodeling and mitochondrial protein turnover. Furthermore, the phosphorylated skeletal muscle-specific CAPN3 acts as a myofibril structural component and may participate in myofibril-based signaling pathways. In the eye, the lens-specific CAPN3, together with CAPN2, is responsible for proteolytic cleavages of alpha and beta-crystallin. Overactivated alpha and beta-crystallin can lead to cataract formation. CAPN3 exists as a homodimer, rather than a heterodimer with the calpain small subunit. It may also form heterodimers with other calpain large subunits. CAPN3 contains a long N-terminal region, 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. Ca2+ binding at EF5 of the CAPN3 PEF domain is a distinct feature not observed in other calpain isoforms.

Pssm-ID: 320065 [Multi-domain] Cd Length: 169 Bit Score: 37.53 E-value: 9.42e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  52 MINEVDADGNGTIDFPEFLNLMAKKmkdtdseEELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLtDEEVEEMIREADV 131
Cdd:cd16190  48 MIALMDTDGSGKLNLQEFRHLWNKI-------KQWQKIFKRYDTDKSGTINSYEMRNAVNDAGFRL-NNQLYDIITMRYA 119

                        90
                ....*....|..
gi 15081767 132 DGDGQINYEEFV 143
Cdd:cd16190 120 DKHMNIDFDSFI 131

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: 38.03 E-value: 1.01e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767   3 DQLT-DEQISEFKEAFSLFDK--DGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKD 79
Cdd:cd16230  26 DQLSpEESQARLGRIVDRMDRagDGDGWVSLAELRAWIAHTQQRHIRDSVSAAWQTYDTDRDGRVGWEELRNATYGHYEP 105

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15081767  80 TDSEEELKEA-------------FRVFDKDQNGFISAAELRHVM-TNLGEKLTDEEVEEMIREADVDGDGQINYEEFV 143
Cdd:cd16230 106 GEEFHDVEDAetykkmlarderrFRVADQDGDSMATREELTAFLhPEEFPHMRDIVVAETLEDLDKNKDGYVQVEEYI 183

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes represent a class of neuron-specific metazoan PI-PLCs that are most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. They are phosphatidylinositol 4,5-bisphosphate-hydrolyzing enzymes that are more sensitive to Ca2+ than other PI-PLC isozymes. They function as calcium sensors activated by small increases in intracellular calcium concentrations. They are also activated through G-protein-coupled receptor (GPCR) stimulation, and further mediate GPCR signalling pathways. PI-PLC-eta isozymes contain an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases. There are two PI-PLC-eta isozymes (1-2). Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.

Pssm-ID: 320035 [Multi-domain] Cd Length: 141 Bit Score: 36.98 E-value: 1.10e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  14 KEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGN-GTIDFPEFLNLMakKMKDTDSeeELKEAFRV 92
Cdd:cd16205   3 KQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNqGTLDFEEFCAFY--KMMSTRR--ELYLLLLS 78

                        90       100
                ....*....|....*....|
gi 15081767  93 FdKDQNGFISAAELRHVMTN 112
Cdd:cd16205  79 Y-SNKKDYLTLEDLARFLEV 97

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: 37.55 E-value: 1.17e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  11 SEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPT----EAELQDMINEV----DADGNGTIDFPEFL-------NLMAK 75
Cdd:cd16177  90 SEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANrpydEKKLQEYTQTIlrmfDLNGDGKLGLSEMArllpvqeNFLLK 169

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 15081767  76 KMKDTDSEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDE 120
Cdd:cd16177 170 FQGMKLSSEEFNAIFAFYDKDGSGYIDENELDALLKDLYEKNKKE 214

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: 37.51 E-value: 1.31e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  11 SEFKEAFSLFDKDGDGCITTKELGTVMRSLGQ--------NPTEAELQDMINEVDADGNGTIDFPEFL-------NLMAK 75
Cdd:cd16176  85 EEFMQTWRKYDADHSGFIEADELKSFLKDLLKkankpfdeSKLEEYTHTMLKMFDSNNDGKLGLTEMArllpvqeNFLLK 164

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 15081767  76 KMKDTDSEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEK 116
Cdd:cd16176 165 FQGVKMCGKEFNKIFELYDQDGNGYIDENELDALLKDLCEK 205

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar proteins; This family represents a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes 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 then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this family is protein Plc1p (also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1) encoded by PLC1 genes from Saccharomyces cerevisiae. ScPlc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that ScPlc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like SCPlc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.

Pssm-ID: 320037 [Multi-domain] Cd Length: 142 Bit Score: 36.84 E-value: 1.47e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  38 RSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMaKKMKDtdsEEELKEAFRVFDKDQNGFISAAELRHVMTNL-GEK 116
Cdd:cd16207  29 RRLHINCSESYLRELFDKADTDKKGYLNFEEFQEFV-KLLKR---RKDIKAIFKQLTKPGSDGLTLEEFLKFLRDVqKED 104

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 15081767 117 LTDEEVEEM----IREADVDGDGQINYEEFVKIMMAK 149
Cdd:cd16207 105 VDRETWEKIfekfARRIDDSDSLTMTLEGFTSFLLSS 141

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: 1.70e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15081767  14 KEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVdADGNGTIDFPEFLNLMAK 75
Cdd:cd16196  74 KRVFKLFDTDGSGSFSSFELRNALNSAGFRLSNATLNALVLRY-SNKDGRISFDDFIMCAVK 134

Penta-EF hand, calcium binding motifs, found in calpain-11 (CAPN11); CAPN11, also termed calcium-activated neutral proteinase 11 (CANP 11), is a mammalian orthologue of micro/m calpain. It is one of the calpain large subunits that appears to be exclusively expressed in certain cells of the testis. It may be involved in regulating calcium-dependent signal transduction events during meiosis and sperm functional processes. CAPN11 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: 320068 [Multi-domain] Cd Length: 169 Bit Score: 36.82 E-value: 1.83e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  52 MINEVDADGNGTIDFPEFlNLMAKKMKdtdseeELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMI-READ 130
Cdd:cd16193  48 MINLMDKDGSGKLGLHEF-KILWKKIK------KWMEIFKECDQDRSGNLNSYEMRLAIEKAGIKMNNRVTEVVVaRYAD 120

                        90       100
                ....*....|....*....|..
gi 15081767 131 ----VDGDGQINYEEFVKIMMA 148
Cdd:cd16193 121 dnmiVDFDSFINCFLRLKAMFA 142

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

Pssm-ID: 320023 [Multi-domain] Cd Length: 278 Bit Score: 36.89 E-value: 2.11e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  50 QDMINEVDADGNGTIDFPEFLNLM------AKKMKDTDSEEELKEAFR-VFDKDQNGFISAAELRHVMTNLGEKLTDEEV 122
Cdd:cd16225 171 KEILHDLDQDGDEKLTLDEFVSLPpgtveeQQAEDDDEWKKERKKEFEeVIDLNHDGKVTKEELEEYMDPRNERHALNEA 250

                        90       100
                ....*....|....*....|..
gi 15081767 123 EEMIREADVDGDGQINYEEFVK 144
Cdd:cd16225 251 KQLIAVADENKDGKLSLEEILK 272

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.

Pssm-ID: 289529 Cd Length: 104 Bit Score: 35.43 E-value: 2.23e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15081767    83 EEELKEAFRVFD--KDQNGFISAAELRHVMTNlgEKLTDEEVEEMIREADVDGDGQINYEEFVKIM 146
Cdd:pfam12763   6 EWEIKKYWEIFSglKPENNKLTGDQVSPVLKN--SRLPDDQLAKIWDLADIDSDGKLDFEEFCIAM 69

EF-hand domain; This domain is found predominantly in DJ binding proteins.

Pssm-ID: 401068 Cd Length: 105 Bit Score: 35.85 E-value: 2.25e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 15081767    88 EAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREADVDGDGQINYEEFV 143
Cdd:pfam08976  24 QEFENFDTLKSNTISRDEFRAICNRHIQILTDEQFDRLWNELPVNAKGRLKYPDFL 79

Penta-EF hand, calcium binding motifs, found in m-type calpain (CAPN2); CAPN2, also termed millimolar-calpain (m-calpain), or calpain-2 catalytic subunit, or calcium-activated neutral proteinase 2 (CANP 2), or calpain large polypeptide L2, or calpain-2 large subunit, 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 CAPN2 in complex with a regulatory subunit encoded by CAPNS1 forms an m-calpain heterodimer. CAPN2 acts as the key protease responsible for N-methyl-d-aspartic acid (NMDA)-induced cytoplasmic polyadenylation element-binding protein 3 (CPEB3) degradation in neurons. It cleaves several components of the focal adhesion complex, such as FAK and talin, triggering disassembly of the complex at the rear of the cell. The stimulation of CAPN2 activity is required for Golgi antiapoptotic proteins (GAAPs) to promote cleavage of FA kinase (FAK), cell spreading, and enhanced migration. calpain 2 is also involved in the onset of glial differentiation. It regulates proliferation, survival, migration, and tumorigenesis of breast cancer cells through a PP2A-Akt-FoxO-p27(Kip1) signaling cascade. Its expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer. Moreover, CAPN2 may play a role in fundamental mitotic functions, such as the maintenance of sister chromatid cohesion. The activation of CAPN2 plays an essential role in hippocampal synaptic plasticity and in learning and memory. In the eye, CAPN2, together with a lens-specific variant of CAPN3, is responsible for proteolytic cleavages of alpha and beta-crystallin. Overactivated alpha and beta-crystallin can lead to cataract formation. Sometimes, CAPN2 compensates for loss of CAPN1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation. The main phosphorylation sites in m-calpain are Ser50 and Ser369/Thr370.

Pssm-ID: 320074 [Multi-domain] Cd Length: 168 Bit Score: 36.42 E-value: 2.30e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  52 MINEVDADGNGTIDFPEFLNLMAKKMKdtdseeeLKEAFRVFDKDQNGFISAAELRHVMTNLGEKLtDEEVEEMIREADV 131
Cdd:cd16199  48 MVDMLDSDGSGKLGLKEFYILWTKIQK-------YQKIYREIDVDRSGTMNSYEMRKALEEAGFKL-PCQLHQVIVARFA 119

                        90
                ....*....|....*.
gi 15081767 132 DGDGQINYEEFVKIMM 147
Cdd:cd16199 120 DDDLIIDFDNFVRCLV 135

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: 36.05 E-value: 2.68e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  10 ISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQnPTEAELQDMINEVDADGNGTIDFPEFLNLMAKkmkdtdseeeLKEA 89
Cdd:cd16182  71 LKKWQAIFKKFDTDRSGTLSSYELRKALESAGF-HLSNKVLQALVLRYADSTGRITFEDFVSCLVR----------LKTA 139

                        90
                ....*....|....*
gi 15081767  90 FRVF---DKDQNGFI 101
Cdd:cd16182 140 FETFsalDKKNEGVI 154

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: 36.53 E-value: 2.81e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  49 LQDMINEVDADGNGTIDFPEFLNLMAKKMKDTDsEEELKEAFRVFDKDQNGFISAAELRH--------------VMTNLG 114
Cdd:cd16227  38 LAVLAKKMDLNDDGFIDRKELKAWILRSFKMLD-EEEANERFEEADEDGDGKVTWEEYLAdsfgyddedneemiKDSTED 116

                        90       100       110
                ....*....|....*....|....*....|
gi 15081767 115 EKLTDEEVEEMIREADVDGDGQINYEEFVK 144
Cdd:cd16227 117 DLKLLEDDKEMFEAADLNKDGKLDKTEFSA 146

phosphatidylserine decarboxylase

Pssm-ID: 215520 [Multi-domain] Cd Length: 644 Bit Score: 36.76 E-value: 2.97e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767   15 EAFSLFDKDGdgciTTKELGTVMRSLG-QNPTEAEL---QDMINEVDADGNGTIDFPEFLNLMaKKMKDTDSEEELKEAF 90
Cdd:PLN02964 147 ESFDLLDPSS----SNKVVGSIFVSCSiEDPVETERsfaRRILAIVDYDEDGQLSFSEFSDLI-KAFGNLVAANKKEELF 221

                         90
                 ....*....|....*.
gi 15081767   91 RVFDKDQNGFISAAEL 106
Cdd:PLN02964 222 KAADLNGDGVVTIDEL 237

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: 3.20e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767   7 DEQISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLNLMAKKMKDTDS---- 82
Cdd:cd16224  32 EEQQKRLKSIIKKIDTDSDGFLTEEELSSWIQQSFRHYALEDAKQQFPEYDKDGDGAVTWDEYNMQMYDRVIDYDEdtvl 111

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15081767  83 EEELKEAFR-VFDKDQNGFISAAELRHVMTNLGE-----------KLTDEEVEEMIREADVDGDGQINYEEFV 143
Cdd:cd16224 112 DDEEEESFRqLHLKDKKRFDKANTDGGPGLNLTEfiafehpeevdYMTEFVIQEALEEHDKDGDGFISLEEFL 184

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: 36.49 E-value: 3.32e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  31 KELGTVMRSLGQNPTEAELQDMINEVD--ADGNGTIDFPEFLNLMAKKMKDTdSEEELKEAFRVFDKDQNGFISAAELRH 108
Cdd:cd16230  19 REVAKEFDQLSPEESQARLGRIVDRMDraGDGDGWVSLAELRAWIAHTQQRH-IRDSVSAAWQTYDTDRDGRVGWEELRN 97

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 15081767 109 VMTNL---GEKLTDEEVEEMIRE-----------ADVDGDGQINYEEF 142
Cdd:cd16230  98 ATYGHyepGEEFHDVEDAETYKKmlarderrfrvADQDGDSMATREEL 145

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: 35.61 E-value: 3.99e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  52 MINEVDADGNGTIDFPEFLNLMAkkmkdtdSEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDEEVEEMIREadV 131
Cdd:cd16186  45 MIAMLDRDHTGKMGFNEFKELWA-------ALNAWKQNFMTVDQDRSGTVEPHELRQAIGAMGYRLSPQTLTTIVKR--Y 115

                        90
                ....*....|..
gi 15081767 132 DGDGQINYEEFV 143
Cdd:cd16186 116 SKNGRIYFDDYV 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: 35.49 E-value: 4.34e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767  52 MINEVDADGNGTIDFPEFLNLMakkmkdtDSEEELKEAFRVFDKDQNGFISAAELRHVMTNLGEKLTDeEVEEMIREADV 131
Cdd:cd16188  48 MVAVMDSDTTGKLGFEEFKYLW-------NNIKKWQGIYKQFDTDRSGTIGSQELPGAFEAAGFHLNE-QLYQMIIRRYS 119

                        90
                ....*....|..
gi 15081767 132 DGDGQINYEEFV 143
Cdd:cd16188 120 DEDGNMDFDNFI 131

EF hand;

Pssm-ID: 433035 [Multi-domain] Cd Length: 25 Bit Score: 32.68 E-value: 5.71e-03

                          10        20
                  ....*....|....*....|....*
gi 15081767    86 LKEAFRVFDKDQNGFISAAELRHVM 110
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRRLL 25

Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1), m-type calpain (CAPN2), and similar proteins; The family includes mu-type calpain (CAPN1) and m-type calpain (CAPN2), both of which are ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine proteases that 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 catalytic subunit CAPN1 or CAPN2 in complex with a regulatory subunit encoded by CAPNS1 forms a mu- or m-calpain heterodimer, respectively.

Pssm-ID: 320064 [Multi-domain] Cd Length: 168 Bit Score: 35.02 E-value: 6.28e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15081767   9 QISEFKEAFSLFDKDGDGCITTKELGTVMRSLGQNPTEAeLQDMINEVDADGNGTIDFPEFLNLMAKKmkdtdseEELKE 88
Cdd:cd16189  71 KIQKYLKIYKKFDTDGSGTMSSYEMRLALEEAGFKLNNQ-LHQVLVARYADQELTIDFDNFVRCLVRL-------ELLFK 142

                        90
                ....*....|...
gi 15081767  89 AFRVFDKDQNGFI 101
Cdd:cd16189 143 IFKQLDKDNTGTI 155