NCBI Conserved Domain Search

calmodulin; Provisional

Pssm-ID: 185504 [Multi-domain] Cd Length: 149 Bit Score: 137.97 E-value: 1.26e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144    1 MSHGFTKEEVAEFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAI-EKYKKG 79
Cdd:PTZ00184   1 MADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMaRKMKDT 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 34014144   80 HRAGELRAVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEFVRLHIEN 148
Cdd:PTZ00184  81 DSEEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMMMSK 149

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 104.10 E-value: 2.14e-29

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  13 FQAAFNRFDKNKDGHISVEELGDVMkqlgknlpEKDLKALISKLDTDGDGKISFEEFLTAIEKYKKGHRAGELRAVFNVL 92
Cdd:COG5126   7 LDRRFDLLDADGDGVLERDDFEALF--------RRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLL 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 34014144  93 DQNGDGYITVDELKESLSKLGesLSQEELEDMIRVADVDQDGKVKYEEFVRLHIE 147
Cdd:COG5126  79 DTDGDGKISADEFRRLLTALG--VSEEEADELFARLDTDGDGKISFEEFVAAVRD 131

centrin; Provisional

Pssm-ID: 185503 [Multi-domain] Cd Length: 158 Bit Score: 99.38 E-value: 2.70e-27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144    4 GFTKEEVAEFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKY--KKGHR 81
Cdd:PTZ00183  10 GLTEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKlgERDPR 89

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 34014144   82 AGELRAvFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEFVRL 144
Cdd:PTZ00183  90 EEILKA-FRLFDDDKTGKISLKNLKRVAKELGETITDEELQEMIDEADRNGDGEISEEEFYRI 151

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

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 75.28 E-value: 5.14e-19

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 34014144  12 EFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAI 73
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 75.60 E-value: 3.22e-18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  11 AEFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKYkkGHRAGELRAVFN 90
Cdd:COG5126  33 RLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTAL--GVSEEEADELFA 110

                        90       100
                ....*....|....*....|.
gi 34014144  91 VLDQNGDGYITVDELKESLSK 111
Cdd:COG5126 111 RLDTDGDGKISFEEFVAAVRD 131

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

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 72.97 E-value: 4.59e-18

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 34014144  84 ELRAVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEFVRLH 145
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62

XopAW family type III secretion system calcium-binding effector;

Pssm-ID: 469301 [Multi-domain] Cd Length: 227 Bit Score: 75.49 E-value: 1.80e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144   11 AEFQAA-FNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEK---YKKGHRAGEL- 85
Cdd:NF041410  26 QQFQKQlFAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAPPpppPPDQAPSTELa 105

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 34014144   86 RAVFNVLDQNGDGYITVDELKESLSKLGESLSQEELedmIRVADVDQDGKVKYEEF 141
Cdd:NF041410 106 DDLLSALDTDGDGSISSDELSAGLTSAGSSADSSQL---FSALDSDGDGSVSSDEL 158

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 72.90 E-value: 3.30e-17

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34014144   1 MSHGFTKEEVAEFQAAFNRFDKNKDGHISVEELGDVMKQLGknLPEKDLKALISKLDTDGDGKISFEEFLTAIEKY 76
Cdd:COG5126  59 MESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALG--VSEEEADELFARLDTDGDGKISFEEFVAAVRDY 132

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: 71.86 E-value: 1.56e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  12 EFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLtAIEKYkkghrAGELRAVFNV 91
Cdd:cd16185   1 ELRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRMFDRDGNGTIDFEEFA-ALHQF-----LSNMQNGFEQ 74

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 34014144  92 LDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEFVRLHI 146
Cdd:cd16185  75 RDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFDPDRGGSLGFDDYIELCI 129

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.

Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 70.77 E-value: 1.95e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  13 FQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAiekYKKGHRAGELRAVFNVL 92
Cdd:cd15898   2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEEL---YKSLTERPELEPIFKKY 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 34014144  93 DQNGDGYITVDELKESLSK-LGESLSQEELEDMIR-VADVDQDGKVKYEEFVRL 144
Cdd:cd15898  79 AGTNRDYMTLEEFIRFLREeQGENVSEEECEELIEkYEPERENRQLSFEGFTNF 132

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: 70.64 E-value: 3.75e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  12 EFQAAFNRFDKNKDGHISVEELGDVMkQLGKNLPEKD--LKALISKLDTDGDGKISFEEFlTAIEKYkkghrAGELRAVF 89
Cdd:cd16180   1 ELRRIFQAVDRDRSGRISAKELQRAL-SNGDWTPFSIetVRLMINMFDRDRSGTINFDEF-VGLWKY-----IQDWRRLF 73

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 34014144  90 NVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEFVRL 144
Cdd:cd16180  74 RRFDRDRSGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRRRGSISFDDFVEA 128

XopAW family type III secretion system calcium-binding effector;

Pssm-ID: 469301 [Multi-domain] Cd Length: 227 Bit Score: 66.24 E-value: 5.47e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144   15 AAFNRFDKNKDGHISVEELGDVMK---QLGKNLPEKDL-KALISKLDTDGDGKISFEEFLTAIEKYKKGHRAGELravFN 90
Cdd:NF041410  67 ELFSDLDSDGDGSLSSDELAAAAPpppPPPDQAPSTELaDDLLSALDTDGDGSISSDELSAGLTSAGSSADSSQL---FS 143

                         90
                 ....*....|....*....
gi 34014144   91 VLDQNGDGYITVDELKESL 109
Cdd:NF041410 144 ALDSDGDGSVSSDELAAAL 162

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: 61.39 E-value: 1.21e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144   8 EEVAEFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKYKKghrageLRA 87
Cdd:cd16180  64 KYIQDWRRLFRRFDRDRSGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRRRGSISFDDFVEACVTLKR------LTD 137

                        90
                ....*....|....*.
gi 34014144  88 VFNVLDQNGDGYITVD 103
Cdd:cd16180 138 AFRKYDTNRTGYATIS 153

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 57.65 E-value: 4.58e-12

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 34014144    14 QAAFNRFDKNKDGHISVEELGDVMKQL--GKNLPEKDLKALISKLDTDGDGKISFEEFLTAI 73
Cdd:pfam13499   5 KEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66

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: 60.39 E-value: 1.17e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144   6 TKEEVAEFQAAFNRFDKNKDGHISVEELGDVMK-QLGKNLPEKDLKALISKLDTDGDGKISFEEFLT-----------AI 73
Cdd:cd16225 126 DKEVLDRYKDRWSQADEPEDGLLDVEEFLSFRHpEHSRGMLKNMVKEILHDLDQDGDEKLTLDEFVSlppgtveeqqaED 205

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 34014144  74 EKYKKGHRAGELRavfNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQDGKVKYEE 140
Cdd:cd16225 206 DDEWKKERKKEFE---EVIDLNHDGKVTKEELEEYMDPRNERHALNEAKQLIAVADENKDGKLSLEE 269

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 56.11 E-value: 1.66e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 34014144    84 ELRAVFNVLDQNGDGYITVDELKESLSKL--GESLSQEELEDMIRVADVDQDGKVKYEEFVRL 144
Cdd:pfam13499   3 KLKEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKDGRISFEEFLEL 65

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: 53.30 E-value: 4.61e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  62 GKISFEEFLTAIEKYKKGHRAGE-LRAVFNVLDQNGDGYITVDELKESLSKLGES-----LSQEELEDMIRVADVDQDGK 135
Cdd:cd16252  15 GSFNYSKFFEYMQKFQTSEQQEEaIRKAFQMLDKDKSGFIEWNEIKYILSTVPSSmpvapLSDEEAEAMIQAADTDGDGR 94


                ....*.
gi 34014144 136 VKYEEF 141
Cdd:cd16252  95 IDFQEF 100

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: 54.74 E-value: 4.62e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  12 EFQAAFNRFDKnKDGHISVEELGDVMKQLGKNLPEKDL-----KALISKLDTDGDGKISFEEFlTAIEKYKKghragELR 86
Cdd:cd15897   1 QLRNVFQAVAG-DDGEISATELQQALSNVGWTHFDLGFsletcRSMIAMMDRDHSGKLNFSEF-KGLWNYIK-----AWQ 73

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  87 AVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADvDQDGKVKYEEFVRLHI 146
Cdd:cd15897  74 EIFRTYDTDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYD-RGRGNIDFDDFIQCCV 132

centrin; Provisional

Pssm-ID: 185503 [Multi-domain] Cd Length: 158 Bit Score: 53.92 E-value: 7.26e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 34014144   12 EFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEK 75
Cdd:PTZ00183  91 EILKAFRLFDDDKTGKISLKNLKRVAKELGETITDEELQEMIDEADRNGDGEISEEEFYRIMKK 154

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: 52.23 E-value: 2.35e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  16 AFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKYKKghRAgELRAVFNVLDQN 95
Cdd:cd16202   5 QFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVQFYNRLTK--RP-EIEELFKKYSGD 81

                        90
                ....*....|....*.
gi 34014144  96 GDgYITVDELKESLSK 111
Cdd:cd16202  82 DE-ALTVEELRRFLQE 96

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: 53.74 E-value: 2.68e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  17 FNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTA--------------IEKYKKGHRA 82
Cdd:cd16226  41 VDKIDKNGDGFVTEEELKDWIKYVQKKYIREDVDRQWKEYDPNKDGKLSWEEYKKAtygflddeeedddlHESYKKMIRR 120

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34014144  83 GELRavFNVLDQNGDGYITVDELK-----ESLSKLGESLSQEELEDMirvaDVDQDGKVKYEEFV 142
Cdd:cd16226 121 DERR--WKAADQDGDGKLTKEEFTaflhpEEFPHMRDIVVQETLEDI----DKNKDGFISLEEYI 179

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

Pssm-ID: 320024 [Multi-domain] Cd Length: 264 Bit Score: 52.59 E-value: 7.53e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  31 EELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKYKKGHRAGELRAVFNVLDQNGDGYITVDELKE--- 107
Cdd:cd16226  19 KEEAKEFDQLTPEESKERLGIIVDKIDKNGDGFVTEEELKDWIKYVQKKYIREDVDRQWKEYDPNKDGKLSWEEYKKaty 98

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 34014144 108 --SLSKLGESLSQEELEDMIR-------VADVDQDGKVKYEEF 141
Cdd:cd16226  99 gfLDDEEEDDDLHESYKKMIRrderrwkAADQDGDGKLTKEEF 141

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: 51.10 E-value: 8.87e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  17 FNRFDKNKDGHISVEELGDVMKQlGKNLP--EKDLKALISKLDTDGDGKISFEEFlTAIEKYKKghragELRAVFNVLDQ 94
Cdd:cd16183   6 FQRVDKDRSGQISATELQQALSN-GTWTPfnPETVRLMIGMFDRDNSGTINFQEF-AALWKYIT-----DWQNCFRSFDR 78

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 34014144  95 NGDGYITVDELKESLSKLGESLSQE------------------------------ELEDMIRVADVDQDG--KVKYEEF 141
Cdd:cd16183  79 DNSGNIDKNELKQALTSFGYRLSDQfydilvrkfdrqgrgtiafddfiqccvvlqTLTDSFRRYDTDQDGwiQISYEQF 157

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: 50.22 E-value: 2.31e-08

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 34014144  84 ELRAVFNVLDQNGDGYITVDELKESLSK-LGESLSQEELEDMIRVADVDQDGKVKYEEFVRLH 145
Cdd:cd16180   1 ELRRIFQAVDRDRSGRISAKELQRALSNgDWTPFSIETVRLMINMFDRDRSGTINFDEFVGLW 63

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: 50.28 E-value: 2.39e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144   8 EEVAEFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLdTDGDGKISFEEFL-------TAIEKYKKGH 80
Cdd:cd16196  68 EDLRSWKRVFKLFDTDGSGSFSSFELRNALNSAGFRLSNATLNALVLRY-SNKDGRISFDDFImcavklkTMFEIFKEKD 146

                        90
                ....*....|....
gi 34014144  81 RAGELRAVFNvLDQ 94
Cdd:cd16196 147 PRGGGRATFN-LDE 159

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: 48.68 E-value: 2.87e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  47 KDLKALISklDTDGDGKISFEEFLTAIEKYKKGhrAGELRAVFNVLDQNGDGYITVDELK---ESLSKLGESLSQEELED 123
Cdd:cd16251   2 KDIEKAPS--AFRAHGSFNYKKFFEHVGLKQKS--EDQIKKVFQILDKDKSGFIEEEELKyilKGFSIAGRDLTDEETKA 77

                        90       100
                ....*....|....*....|.
gi 34014144 124 MIRVADVDQDGKVKYEEFVRL 144
Cdd:cd16251  78 LLAAGDTDGDGKIGVEEFATL 98

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: 48.30 E-value: 4.01e-08

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 34014144   4 GFTKEEVAEFQAAFNRFDKNKDGHISVEELGDVMKQL---GKNLPEKDLKALISKLDTDGDGKISFEEFLT 71
Cdd:cd16251  27 GLKQKSEDQIKKVFQILDKDKSGFIEEEELKYILKGFsiaGRDLTDEETKALLAAGDTDGDGKIGVEEFAT 97

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: 48.04 E-value: 4.64e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34014144      6 TKEEVAEFQAAFNRFDKNKDGHISVEELGDVMKQLGknLPEKDLkALISKL-DTDGDGKISFEEF 69
Cdd:smart00027   5 SPEDKAKYEQIFRSLDKNQDGTVTGAQAKPILLKSG--LPQTLL-AKIWNLaDIDNDGELDKDEF 66

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: 46.83 E-value: 6.71e-08

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  13 FQAAFNRFDKNKDGHISVEELGDVMKQLGknLPEKDLKALISKLDTDGDGKISFEEFLTA 72
Cdd:cd00052   1 YDQIFRSLDPDGDGLISGDEARPFLGKSG--LPRSVLAQIWDLADTDKDGKLDKEEFAIA 58

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: 48.80 E-value: 6.79e-08

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 34014144   9 EVAEFQA----------AFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEF 69
Cdd:cd16184  55 DIYEFQAlwnyiqqwkqVFQQFDRDRSGSIDENELHQALSQMGYRLSPQFVQFLVSKYDPRARRSLTLDQF 125

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: 48.15 E-value: 8.14e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  17 FNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTD-GDGKISFEEFLTAiekYKKGHRAGELRAVFNVLDQN 95
Cdd:cd16205   6 FEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDdNQGTLDFEEFCAF---YKMMSTRRELYLLLLSYSNK 82

                        90
                ....*....|
gi 34014144  96 GDgYITVDEL 105
Cdd:cd16205  83 KD-YLTLEDL 91

EF-hand domain pair;

Pssm-ID: 404678 [Multi-domain] Cd Length: 54 Bit Score: 45.77 E-value: 1.07e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 34014144    96 GDGYITVDELKESLSKLG-ESLSQEELEDMIRVADVDQDGKVKYEEFVRL 144
Cdd:pfam13833   1 EKGVITREELKRALALLGlKDLSEDEVDILFREFDTDGDGYISFDEFCVL 50

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: 48.89 E-value: 1.49e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  17 FNRFDKNKDGHISVEELGDVMKQLGKNLP---------EKDLKALISKLDTDGDGKISFEE----------FLTAIEKYK 77
Cdd:cd15902   5 WMHFDADGNGYIEGKELDSFLRELLKALNgkdktddevAEKKKEFMEKYDENEDGKIEIRElanilpteenFLLLFRREQ 84

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34014144  78 KGHRAGELRAVFNVLDQNGDGYITVDEL----KESLSKLGESLSQEELED----MIRVADVDQDGKVKYEEFVRL 144
Cdd:cd15902  85 PLISSVEFMKIWRKYDTDGSGFIEAKELkgflKDLLLKNKKHVSPPKLDEytklILKEFDANKDGKLELDEMAKL 159

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: 46.65 E-value: 1.51e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  65 SFEEFLTAIEKYKKGhrAGELRAVFNVLDQNGDGYITVDELK---ESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEF 141
Cdd:cd16255  18 NFKKFFATSGLSKKS--ADDVKKVFEIIDQDKSGFIEEEELKlflQNFSSGARELTDAETKAFLKAGDSDGDGKIGVEEF 95


                ...
gi 34014144 142 VRL 144
Cdd:cd16255  96 QAL 98

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: 46.01 E-value: 3.17e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 34014144   4 GFTKEEVAEFQAAFNRFDKNKDGHISVEELGDVMKQL---GKNLPEKDLKALISKLDTDGDGKISFEEFLTAI 73
Cdd:cd16253  27 GLSKKSPADIKKVFNILDQDKSGFIEEEELKLFLKNFsdgARVLSDKETKNFLAAGDSDGDGKIGVDEFKSMV 99

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: 47.73 E-value: 3.27e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  11 AEFQAAFNRFDKNKDGHISVEELG----DVMKQLGKNLPEKDL----KALISKLDTDGDGKISFEEF-----------LT 71
Cdd:cd15902  90 VEFMKIWRKYDTDGSGFIEAKELKgflkDLLLKNKKHVSPPKLdeytKLILKEFDANKDGKLELDEMakllpvqenflLK 169

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 34014144  72 AIEKYKKGHRAGELRAVFNVLDQNGDGYITVDELKESLSKLGE----SLSQEELED----MIRVADVDQDGKVKYEEFV 142
Cdd:cd15902 170 FQILGAMDLTKEDFEKVFEHYDKDNNGVIEGNELDALLKDLLEknkaDIDKPDLENfrdaILRACDKNKDGKIQKTELA 248

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: 46.83 E-value: 4.27e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  19 RFDK--NKDGHISVEELGDVMKQ-LGKNLPEKD------LKALISKLDTDGDGKISFEEFLTAIEKYKKghrageLRAVF 89
Cdd:cd16182   5 LFEKlaGEDEEIDAVELQKLLNAsLLKDMPKFDgfsletCRSLIALMDTNGSGRLDLEEFKTLWSDLKK------WQAIF 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 34014144  90 NVLDQNGDGYITVDELKESLSKLGESLSQEELEDMI-RVAdvDQDGKVKYEEFV 142
Cdd:cd16182  79 KKFDTDRSGTLSSYELRKALESAGFHLSNKVLQALVlRYA--DSTGRITFEDFV 130

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 43.78 E-value: 9.26e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 34014144    46 EKDLKALISKLDTDGDGKISFEEFLTAIEKYKKGH--RAGELRAVFNVLDQNGDGYITVDELKE 107
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLEEGEplSDEEVEELFKEFDLDKDGRISFEEFLE 64

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: 44.43 E-value: 9.59e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 34014144   4 GFTKEEVAEFQAAFNRFDKNKDGHISVEELGDVMKQL---GKNLPEKDLKALISKLDTDGDGKISFEEFLTAI 73
Cdd:cd16254  27 GLKKKSADDVKKVFHILDKDKSGFIEEDELKFVLKGFspdGRDLSDKETKALLAAGDKDGDGKIGIDEFATLV 99

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: 46.51 E-value: 1.01e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  25 DGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAI----------------EKYKKGHRAGELRav 88
Cdd:cd16230  51 DGWVSLAELRAWIAHTQQRHIRDSVSAAWQTYDTDRDGRVGWEELRNATyghyepgeefhdvedaETYKKMLARDERR-- 128

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 34014144  89 FNVLDQNGDGYITVDELK-----ESLSKLGESLSQEELEDMirvaDVDQDGKVKYEEFV 142
Cdd:cd16230 129 FRVADQDGDSMATREELTaflhpEEFPHMRDIVVAETLEDL----DKNKDGYVQVEEYI 183

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: 45.31 E-value: 1.13e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 34014144  17 FNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGD-GKISFEEFLT 71
Cdd:cd16221   6 FDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNqGTLGFEEFCA 61

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: 45.02 E-value: 1.24e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  17 FNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGD-GKISFEEFLTAiekYKKGHRAGELRAVFNVLDQN 95
Cdd:cd16220   6 FEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENqGTLTFEEFCVF---YKMMSLRRDLYLLLLSYSDK 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 34014144  96 GDgYITVDELKESLSKLGE--SLSQEELEDMIRVADVDQDGKVK 137
Cdd:cd16220  83 KD-HLTVEELAQFLKVEQKmnNVTTEYCLDIIKKFEVSEENKEQ 125

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

Pssm-ID: 320025 [Multi-domain] Cd Length: 263 Bit Score: 46.16 E-value: 1.31e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  17 FNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFL--------TAIEKYKKGHRAGELRAV 88
Cdd:cd16227  42 AKKMDLNDDGFIDRKELKAWILRSFKMLDEEEANERFEEADEDGDGKVTWEEYLadsfgyddEDNEEMIKDSTEDDLKLL 121

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 34014144  89 ------FNVLDQNGDGYITVDELKESLS-KLGESLSQEELEDMIRVADVDQDGKVKYEEFV 142
Cdd:cd16227 122 eddkemFEAADLNKDGKLDKTEFSAFQHpEEYPHMHPVLIEQTLRDKDKDNDGFISFQEFL 182

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

Pssm-ID: 320056 [Multi-domain] Cd Length: 165 Bit Score: 45.44 E-value: 1.39e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  25 DGHISVEELGDVMKQLG-----KNLPEKDLKALISKLDTDGDGKISFEEF---LTAIEKYKkghragelrAVFNVLDQNG 96
Cdd:cd16181  13 DGQIDADELQRCLTQSGisgnyQPFSLETCRLMIAMLDRDHSGKMGFNEFkelWAALNQWK---------TTFMQYDRDR 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 34014144  97 DGYITVDELKESLSKLGESLSQEELEDMIRvaDVDQDGKVKYEEFVRL 144
Cdd:cd16181  84 SGTVEPQELQQAIRSFGYNLSPQALNVIVK--RYSKNGRITFDDFVAC 129

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: 44.86 E-value: 2.00e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  24 KDGHISVEELGDVMKQLGKN-----LPEKDLKALISKLDTDGDGKISFEEF---LTAIEKYKKGhragelravFNVLDQN 95
Cdd:cd16186  12 QDGEVDAEELQRCLTQSGINgtytpFSLETCRIMIAMLDRDHTGKMGFNEFkelWAALNAWKQN---------FMTVDQD 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 34014144  96 GDGYITVDELKESLSKLGESLSQEELEDMIRvaDVDQDGKVKYEEFV 142
Cdd:cd16186  83 RSGTVEPHELRQAIGAMGYRLSPQTLTTIVK--RYSKNGRIYFDDYV 127

EF-hand domain pair;

Pssm-ID: 404678 [Multi-domain] Cd Length: 54 Bit Score: 42.69 E-value: 2.02e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 34014144    24 KDGHISVEELGDVMKQLG-KNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKY 76
Cdd:pfam13833   1 EKGVITREELKRALALLGlKDLSEDEVDILFREFDTDGDGYISFDEFCVLLERR 54

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: 44.88 E-value: 3.47e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  17 FNRFDKNKDGHISVEELGDVMKqlgknlPE-----KDLKA--LISKLDTDGDGKISFEEFLTAI-----EKYKKGHRAGE 84
Cdd:cd16226 125 WKAADQDGDGKLTKEEFTAFLH------PEefphmRDIVVqeTLEDIDKNKDGFISLEEYIGDMyrdddEEEDPDWVKSE 198

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 34014144  85 LRAVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQDGKVKYEE 140
Cdd:cd16226 199 REQFKEFRDKNKDGKMDREEVKDWILPEDYDHAEAEAKHLIYEADDDKDGKLTKEE 254

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: 43.73 E-value: 5.36e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  50 KALISKLDTDGDGKISFEEFLT---AIEKYKKghragelraVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDM-I 125
Cdd:cd16195  46 RSMVALMDLSVNGRLSLEEFSRlwkKLRKYKD---------IFQKADVSKSGFLSLSELRNAIQAAGIRVSDDLLNLMaL 116

                        90
                ....*....|....*....
gi 34014144 126 RVADVdqDGKVKYEEFVRL 144
Cdd:cd16195 117 RYGDS--SGRISFESFICL 133

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.

Pssm-ID: 238009 [Multi-domain] Cd Length: 67 Bit Score: 41.44 E-value: 7.26e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 34014144  89 FNVLDQNGDGYITVDELKESLSKLGesLSQEELEDMIRVADVDQDGKVKYEEFV 142
Cdd:cd00052   5 FRSLDPDGDGLISGDEARPFLGKSG--LPRSVLAQIWDLADTDKDGKLDKEEFA 56

phosphatidylserine decarboxylase

Pssm-ID: 215520 [Multi-domain] Cd Length: 644 Bit Score: 44.08 E-value: 8.41e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34014144   50 KALISKLDTDGDGKISFEEFLTAIEKYKKGHRAGELRAVFNVLDQNGDGYITVDELKESLSKlgeslsQEELEDMI 125
Cdd:PLN02964 182 RRILAIVDYDEDGQLSFSEFSDLIKAFGNLVAANKKEELFKAADLNGDGVVTIDELAALLAL------QQEQEPII 251

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: 42.13 E-value: 9.73e-06

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34014144  16 AFNRFDKNKDGHISVEELGDVMKQLGKNLP-----EKDLKALISKLDTDGDGKISFEEFLTAIEK 75
Cdd:cd16252  42 AFQMLDKDKSGFIEWNEIKYILSTVPSSMPvaplsDEEAEAMIQAADTDGDGRIDFQEFSDMVKK 106

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: 43.46 E-value: 1.21e-05

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 34014144  85 LRAVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEFV 142
Cdd:cd16227  38 LAVLAKKMDLNDDGFIDRKELKAWILRSFKMLDEEEANERFEEADEDGDGKVTWEEYL 95

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC)-like proteins; The SPARC protein family represents a diverse group of proteins that share a follistatin-like (FS) domain and an extracellular calcium-binding (EC) domain with two EF-hand motifs. It includes SPARC (for secreted protein acidic and rich in cysteine, also termed osteonectin/ON, or basement-membrane protein 40/BM-40), SPARC-like protein 1 (for secreted protein, acidic and rich in cysteines-like 1/ SPARCL1, also termed high endothelial venule protein/Hevi, or MAST 9, or SC-1, or RAGS-1, or QR1, or ECM 2), testicans 1, 2, and 3 (also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycans, or SPOCK), secreted modular calcium-binding protein SMOC-1 (also termed SPARC-related modular calcium-binding protein 1) and SMOC-2 (also termed SPARC-related modular calcium-binding protein 2, or smooth muscle-associated protein 2/SMAP-2), follistatin-related protein 1 (FRP-1, also termed follistatin-like protein 1/fstl-1, TSC-36/Flik, TGF-beta inducible protein). The SPARC proteins have been implicated in modulating cell interaction with the extracellular milieu, including regulation of extracellular matrix assembly and deposition, counter-adhesion, effects on extracellular protease activity, and modulation of growth factor/cytokine signaling pathways, as well as in development and disease.

Pssm-ID: 320009 Cd Length: 107 Bit Score: 41.59 E-value: 1.31e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 34014144   7 KEEVAEFQaaFNRFDKNKDGHISVEELGDVMKQLgkNLPEKDLKALISKLDTDGDGKISFEEFL 70
Cdd:cd00252  43 RKEIAQWE--FDNLDNNKDGKLDKRELAPFRAPL--MPLEHCARGFFESCDLNKDKKISLQEWL 102

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 42.09 E-value: 1.48e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34014144  80 HRAGELRAVFNVLDQNGDGYITVDELkeslsklgESLSQEELEDMIRVADVDQDGKVKYEEFVRLH 145
Cdd:COG5126   2 LQRRKLDRRFDLLDADGDGVLERDDF--------EALFRRLWATLFSEADTDGDGRISREEFVAGM 59

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: 41.98 E-value: 1.61e-05

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 34014144  85 LRAVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQ-DGKVKYEEFV 142
Cdd:cd16205   2 LKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDnQGTLDFEEFC 60

EF-hand domain;

Pssm-ID: 463869 [Multi-domain] Cd Length: 30 Bit Score: 39.47 E-value: 1.62e-05

                          10        20        30
                  ....*....|....*....|....*....|
gi 34014144    12 EFQAAFNRFDKNKDGHISVEELGDVMKQLG 41
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination.

Pssm-ID: 320058 [Multi-domain] Cd Length: 165 Bit Score: 42.24 E-value: 1.76e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  10 VAEFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKYKKghrageLRAVF 89
Cdd:cd16183  66 ITDWQNCFRSFDRDNSGNIDKNELKQALTSFGYRLSDQFYDILVRKFDRQGRGTIAFDDFIQCCVVLQT------LTDSF 139

                        90
                ....*....|...
gi 34014144  90 NVLDQNGDGYITV 102
Cdd:cd16183 140 RRYDTDQDGWIQI 152

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: 42.69 E-value: 1.86e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  17 FNRFDKNKDGHISVEELgdVMKQLGKNLP---EKDLKALISKLDTDGDGKISFEEFL--TAIEKYKKGHRAgELRAVFNV 91
Cdd:cd16227 128 FEAADLNKDGKLDKTEF--SAFQHPEEYPhmhPVLIEQTLRDKDKDNDGFISFQEFLgdRAGHEDKEWLLV-EKDRFDED 204

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 34014144  92 LDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEFVRLH 145
Cdd:cd16227 205 YDKDGDGKLDGEEILSWLVPDNEEIAEEEVDHLFASADDDHDDRLSFDEILDHH 258

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: 43.06 E-value: 1.89e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  24 KDGHISVEE-----LGDVMK---QLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKYKKGH---RAGELRAVFNVL 92
Cdd:cd16225   3 RDGHLNKEFhkevfLGNEKEefeEDSEPKKRKKLKEIFKKVDVNTDGFLSAEELEDWIMEKTQEHfqeAVEENEQIFKAV 82

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 34014144  93 DQNGDGYITVDELKESLSKlGESLSQEELEDMIRV-----------------------ADVDQDGKVKYEEFVR-LHIE 147
Cdd:cd16225  83 DTDKDGNVSWEEYRVHFLL-SKGYSEEEAEEKIKNneelkldeddkevldrykdrwsqADEPEDGLLDVEEFLSfRHPE 160

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: 42.19 E-value: 1.96e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  10 VAEFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEkDLKALISKLDTDGDGKISFEEFLT---AIEKYKKghragelr 86
Cdd:cd16195  72 LRKYKDIFQKADVSKSGFLSLSELRNAIQAAGIRVSD-DLLNLMALRYGDSSGRISFESFIClmlRLECMAK-------- 142

                        90
                ....*....|....*....
gi 34014144  87 aVFNVLDQNGDG-YITVDE 104
Cdd:cd16195 143 -IFRNLSKDGGGiYLTESE 160

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: 40.72 E-value: 2.15e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144     63 KISFEEfltaIEKYKKghragelraVFNVLDQNGDGYITVDELKESLSKLGesLSQEELEDMIRVADVDQDGKVKYEEFV 142
Cdd:smart00027   3 AISPED----KAKYEQ---------IFRSLDKNQDGTVTGAQAKPILLKSG--LPQTLLAKIWNLADIDNDGELDKDEFA 67

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: 41.01 E-value: 2.22e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 34014144  82 AGELRAVFNVLDQNGDGYITVDELK---ESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEF 141
Cdd:cd16253  33 PADIKKVFNILDQDKSGFIEEEELKlflKNFSDGARVLSDKETKNFLAAGDSDGDGKIGVDEF 95

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.

Pssm-ID: 320021 [Multi-domain] Cd Length: 267 Bit Score: 42.43 E-value: 2.50e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  32 ELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKYKKGHRAGELRAVFNVLDQNGDGYITVDELK----- 106
Cdd:cd15899  20 EEAEEFDQLTPEESKRRLGVIVSKMDVDKDGFISAKELHSWILESFKRHAMEESKEQFRAVDPDEDGHVSWDEYKndtyg 99

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 34014144 107 -------ESLSKLGESLSQEEL----EDMIRVADVDQDGKVKYEEF 141
Cdd:cd15899 100 svgddeeNVADNIKEDEEYKKLllkdKKRFEAADQDGDLILTLEEF 145

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: 42.04 E-value: 2.64e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  10 VAEFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKdLKALISKLDTDGDGKISFEEFLTAIEKYKKGHRAgelravF 89
Cdd:cd16188  72 IKKWQGIYKQFDTDRSGTIGSQELPGAFEAAGFHLNEQ-LYQMIIRRYSDEDGNMDFDNFISCLVRLDAMFRA------F 144

                        90
                ....*....|...
gi 34014144  90 NVLDQNGDGYITV 102
Cdd:cd16188 145 KSLDKDGTGQIQV 157

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: 40.58 E-value: 3.10e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  78 KGHRAGELRAVFNVLDQNGDGYITVDELK---ESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEFVRL 144
Cdd:cd16254  29 KKKSADDVKKVFHILDKDKSGFIEEDELKfvlKGFSPDGRDLSDKETKALLAAGDKDGDGKIGIDEFATL 98

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: 41.48 E-value: 3.35e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  12 EFQAAFNRFDKNKDGHISVEELgdvmKQL-----GKNLPEKDLKALISKLDTDGDGKISFEEFlTAIEKYKKghragELR 86
Cdd:cd16184   1 EVQQWFQAVDRDRSGKISAKEL----QQAlvngnWSHFNDETCRLMIGMFDKDKSGTIDIYEF-QALWNYIQ-----QWK 70

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  87 AVFNVLDQNGDGYITVDELKESLSKLGESLSQE------------------------------ELEDMIRVADVDQDG-- 134
Cdd:cd16184  71 QVFQQFDRDRSGSIDENELHQALSQMGYRLSPQfvqflvskydprarrsltldqfiqvcvqlqSLTDAFRQRDTQMTGti 150

                       170
                ....*....|....
gi 34014144 135 KVKYEEFVRLHIEN 148
Cdd:cd16184 151 TISYEDFLTMALLN 164

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: 41.42 E-value: 3.46e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  12 EFQAAFNRFdKNKDGHISVEELGDV-----MKQLGKNLPEKDL-KALISKLDTDGDGKISFEEF---LTAIEKYKKghra 82
Cdd:cd16196   1 RLRRLFDKI-AGEDMEIDAYELQDIlntafKKDFPFDGFSLDAcRSMVAMMDVDRSGKLGFEEFkklWEDLRSWKR---- 75

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 34014144  83 gelraVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMI-RVADVdqDGKVKYEEFV 142
Cdd:cd16196  76 -----VFKLFDTDGSGSFSSFELRNALNSAGFRLSNATLNALVlRYSNK--DGRISFDDFI 129

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.

Pssm-ID: 320021 [Multi-domain] Cd Length: 267 Bit Score: 42.04 E-value: 3.54e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  49 LKALISKLDTDGDGKISFEEFLTAIEKYKKGHRAGELRAV-----FNVLDQNGDGYITVDELKESLSKLGESLSQEELED 123
Cdd:cd15899 162 IKETLEDLDKNGDGFISLEEFISDPYSADENEEEPEWVKVekerfVELRDKDKDGKLDGEELLSWVDPSNQEIALEEAKH 241

                        90       100
                ....*....|....*....|..
gi 34014144 124 MIRVADVDQDGKVKYEEFVRLH 145
Cdd:cd15899 242 LIAESDENKDGKLSPEEILDNH 263

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: 41.66 E-value: 4.41e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144   8 EEVAEFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAI-------------- 73
Cdd:cd15899  32 ESKRRLGVIVSKMDVDKDGFISAKELHSWILESFKRHAMEESKEQFRAVDPDEDGHVSWDEYKNDTygsvgddeenvadn 111

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34014144  74 ----EKYKKGHRAGELRavFNVLDQNGDGYITVDEL-----KESLSKLGESLSQEELEDMirvaDVDQDGKVKYEEFV 142
Cdd:cd15899 112 ikedEEYKKLLLKDKKR--FEAADQDGDLILTLEEFlaflhPEESPYMLDFVIKETLEDL----DKNGDGFISLEEFI 183

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: 5.55e-05

                           10        20
                   ....*....|....*....|....*....
gi 34014144     12 EFQAAFNRFDKNKDGHISVEELGDVMKQL 40
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

EF-hand domain;

Pssm-ID: 463869 [Multi-domain] Cd Length: 30 Bit Score: 37.93 E-value: 6.63e-05

                          10        20        30
                  ....*....|....*....|....*....|
gi 34014144    84 ELRAVFNVLDQNGDGYITVDELKESLSKLG 113
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30

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: 40.49 E-value: 7.21e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  50 KALISKLDTDGDGKISFEEFLTAIEKYKKghrageLRAVFNVLDQNGDGYITVDELKESLSKLGESLSqEELEDMIRVAD 129
Cdd:cd16188  46 RSMVAVMDSDTTGKLGFEEFKYLWNNIKK------WQGIYKQFDTDRSGTIGSQELPGAFEAAGFHLN-EQLYQMIIRRY 118

                        90
                ....*....|...
gi 34014144 130 VDQDGKVKYEEFV 142
Cdd:cd16188 119 SDEDGNMDFDNFI 131

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: 40.75 E-value: 9.43e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  17 FNRFDKNKDGHISVEELGD-VMKQLGKNLPE--KDLKALISKLDTDGDGKISFEEFLT-----------AIEKYKKGHRA 82
Cdd:cd16225  40 FKKVDVNTDGFLSAEELEDwIMEKTQEHFQEavEENEQIFKAVDTDKDGNVSWEEYRVhfllskgyseeEAEEKIKNNEE 119

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  83 GEL-----------RAVFNVLDQNGDGYITVDEL---------KESLSKLgeslsqeeLEDMIRVADVDQDGKVKYEEFV 142
Cdd:cd16225 120 LKLdeddkevldryKDRWSQADEPEDGLLDVEEFlsfrhpehsRGMLKNM--------VKEILHDLDQDGDEKLTLDEFV 191


                ..
gi 34014144 143 RL 144
Cdd:cd16225 192 SL 193

EF-hand, extracellular calcium-binding (EC) motif, found in testicans; Testicans are nervous system-expressed proteoglycans that play important roles in the regulation of protease activity, as well as in the determination of age at menarche. Testican-1 (TICN1, also termed protein SPOCK) is a secreted chimeric proteoglycan that is highly expressed in brain and carries both chondroitin and heparan sulfate glycosaminoglycan side chains. It has been implicated in autoimmune disease. It also acts as a regulator of bone morphogenetic protein (BMP) signaling and show critical functions in the nervous system. Testican-2 (TICN2, also termed protein SPOCK2) is an extracellular heparan sulphate proteoglycan highly expressed in brain. It may play regulatory roles in the development of the central nervous system. It also participates in diverse steps of neurogenesis. TICN1, but not TICN2, inhibits cathepsin L. TICN1 also inhibits attachment and neurite outgrowth in cultures of N2A neuroblastoma cells, While TICN2 is able to inhibit neurite outgrowth from primary cerebellar cells. Testicans contain an N-terminal signal peptide, a testican-specific domain followed by a follistatin-like (FS) domain, an extracellular calcium-binding (EC) domain including a pair of EF hands, a thyroglobulin-like domain (TY), and a C-terminal region with two putative glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr orTyr in the +Y position of EF hand 2 in testican-2 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ with low affinity. The substitution of a ligating Asp residue by Phe or Tyr in the +Y position of EF-hand 2 in testicans could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.

Pssm-ID: 320011 Cd Length: 108 Bit Score: 39.28 E-value: 9.68e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 34014144  17 FNRFDKNKDGHISVEELGDVmkQLGKNlpEKDLKALISKLDTDGDGKISFEEFLTAIEKYK 77
Cdd:cd16232  52 FNQLDTNNDLHLSQSELYDL--ELDKY--EPCIKPFLDSCDRNKDGKISSDEWCDCFQRAD 108

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: 40.63 E-value: 1.06e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  11 AEFQAAFNRFDKNKDGHISVEEL----GDVMKQLGKNLPEKDL----KALISKLDTDGDGKISF----------EEFLTA 72
Cdd:cd16177  90 SEFMEAWRKYDTDRSGYIEANELkgflSDLLKKANRPYDEKKLqeytQTILRMFDLNGDGKLGLsemarllpvqENFLLK 169

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 34014144  73 IEKYKKGhrAGELRAVFNVLDQNGDGYITVDELKESLSKLGESLSQE 119
Cdd:cd16177 170 FQGMKLS--SEEFNAIFAFYDKDGSGYIDENELDALLKDLYEKNKKE 214

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: 38.94 E-value: 1.13e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 34014144   4 GFTKEEVAEFQAAFNRFDKNKDGHISVEELGDVMKQL---GKNLPEKDLKALISKLDTDGDGKISFEEF 69
Cdd:cd16255  27 GLSKKSADDVKKVFEIIDQDKSGFIEEEELKLFLQNFssgARELTDAETKAFLKAGDSDGDGKIGVEEF 95

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: 39.89 E-value: 1.24e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  24 KDGHISVEELGDVMKQLG-----KNLPEKDLKALISKLDTDGDGKISFEEFltaiekykkghraGELRAVFNVLDQN--- 95
Cdd:cd16187  12 QDGQIDADELQRCLTQSGiaggyKPFNLETCRLMISMLDRDMSGTMGFNEF-------------KELWAVLNGWRQHfis 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 34014144  96 --GDGYITVD--ELKESLSKLGESLSQEELEDMIRvaDVDQDGKVKYEEFV 142
Cdd:cd16187  79 fdSDRSGTVDpqELQKALTTMGFRLSPQAVNSIAK--RYSTNGKITFDDYI 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: 36.99 E-value: 1.24e-04

                          10        20
                  ....*....|....*....|....*....
gi 34014144    12 EFQAAFNRFDKNKDGHISVEELGDVMKQL 40
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29

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: 39.84 E-value: 1.25e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  12 EFQAAFNRFdKNKDGHISVEELGDVMKQLGKNlpEKDLK----------ALISKLDTDGDGKISFEEFLTAIEKYKkghr 81
Cdd:cd16190   1 QFRNIFQQI-AGDDMEISADELRSVLNRVVKK--HKDLKtegftlescrSMIALMDTDGSGKLNLQEFRHLWNKIK---- 73

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 34014144  82 agELRAVFNVLDQNGDGYITVDELKESLSKLGESLSQeELEDMIRVADVDQDGKVKYEEFV 142
Cdd:cd16190  74 --QWQKIFKRYDTDKSGTINSYEMRNAVNDAGFRLNN-QLYDIITMRYADKHMNIDFDSFI 131

phosphatidylserine decarboxylase

Pssm-ID: 215520 [Multi-domain] Cd Length: 644 Bit Score: 40.61 E-value: 1.64e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 34014144   86 RAVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEFVRL 144
Cdd:PLN02964 182 RRILAIVDYDEDGQLSFSEFSDLIKAFGNLVAANKKEELFKAADLNGDGVVTIDELAAL 240

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: 39.14 E-value: 1.67e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 34014144  85 LRAVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQD-GKVKYEEF 141
Cdd:cd16221   2 LKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNqGTLGFEEF 59

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: 40.08 E-value: 1.75e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  13 FQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDL----------KALISKLDTDGDGKISFEE-----------FLT 71
Cdd:cd16178   1 FAEIWQHFDADESGYIEGKELDNFFKDLLKKLGTKDTisadevqdvkECFMSAYDVTGDGRIQIQElaniilpddenFLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  72 AIEKYKKGHRAGELRAVFNVLDQNGDGYITVDELKESLSKL----GESLSQEELED----MIRVADVDQDGKVKYEEFVR 143
Cdd:cd16178  81 FFRREEPLDSSVEFMRIWRKYDADSSGYISAAELKNFLRDLflqhKKVITEDKLDEytdtMMKIFDKNKDGRLDLNDMAR 160


                .
gi 34014144 144 L 144
Cdd:cd16178 161 I 161

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: 39.72 E-value: 2.24e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  14 QAAFNRFDKNKDGHISVEE-LGDVMKQLGKN------LPEKDlkALISKLDTDGDGKISFEEFLTAIEKYKKGHRAGELR 86
Cdd:cd16224 164 QEALEEHDKDGDGFISLEEfLGDYRKDPTANedpewiIVEKD--RFVNDYDKDNDGKLDPQELLPWVVPNNYGIAQEEAL 241

                        90       100
                ....*....|....*....|..
gi 34014144  87 AVFNVLDQNGDGYITVDELKES 108
Cdd:cd16224 242 HLIDEMDLNGDGRLSEEEILEN 263

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: 39.73 E-value: 2.40e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 34014144  18 NRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFL 70
Cdd:cd15899 208 ELRDKDKDGKLDGEELLSWVDPSNQEIALEEAKHLIAESDENKDGKLSPEEIL 260

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: 38.85 E-value: 2.45e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 34014144  85 LRAVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQD-GKVKYEEF 141
Cdd:cd16220   2 VKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENqGTLTFEEF 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: 36.20 E-value: 2.64e-04

                           10        20
                   ....*....|....*....|....*...
gi 34014144     48 DLKALISKLDTDGDGKISFEEFLTAIEK 75
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKA 28

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

Pssm-ID: 320027 [Multi-domain] Cd Length: 267 Bit Score: 39.48 E-value: 3.03e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  18 NRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKYKKGHRAGELRAV--------- 88
Cdd:cd16229  42 DRIDDDKDGFVTTEELKAWIKRVQKRYIYENVAKVWKDYDLNKDNKISWEEYKQATYGYYLGNPEEFQDATdqfsfkkml 121

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34014144  89 ------FNVLDQNGDGYITVDELK-----ESLSKLGESLSQEELEDMirvaDVDQDGKVKYEEFV 142
Cdd:cd16229 122 prderrFKAADLDGDLAATREEFTaflhpEEFEHMKDIVVLETLEDI----DKNGDGFVDEDEYI 182

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (PLCD4), or phospholipase C-delta-4 (PLC-delta-4), is expressed in various tissues with the highest levels detected selectively in the brain, skeletal muscle, testis and kidney. It plays a significant role in cell growth, cell proliferation, tumorigenesis, and in an early stage of fertilization. PI-PLC-delta4 may function as a key enzyme in the regulation of PtdIns(4,5)P2 levels and Ca2+ metabolism in nuclei in response to growth factors, and its expression may be partially regulated by an increase in cytoplasmic Ca2+. Moreover, PI-PLC-delta4 binds glutamate receptor-interacting protein1 (GRIP1) in testis and is required for calcium mobilization essential for the zona pellucida-induced acrosome reaction in sperm. Overexpression or dysregulated expression of PLCdelta4 may initiate oncogenesis in certain tissues through upregulating erbB1/2 expression, extracellular signal-regulated kinase (ERK) signaling pathway, and proliferation in MCF-7 cells. PI-PLC-delta4 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, and a 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. Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4.

Pssm-ID: 320049 [Multi-domain] Cd Length: 140 Bit Score: 38.67 E-value: 3.04e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  17 FNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFltaIEKYKKGHRAGELRAVFNVLDQNG 96
Cdd:cd16219   6 FQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSESGTLEGEEF---VLFYKALTQREDVLKIFQDFSADG 82

                        90       100
                ....*....|....*....|....*..
gi 34014144  97 DgyitvdelKESLSKLGESLSQEELED 123
Cdd:cd16219  83 Q--------KLTLLEFVDFLQQEQLER 101

EF hand;

Pssm-ID: 433035 [Multi-domain] Cd Length: 25 Bit Score: 36.14 E-value: 3.20e-04

                          10        20
                  ....*....|....*....|....*
gi 34014144    13 FQAAFNRFDKNKDGHISVEELGDVM 37
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRRLL 25

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: 39.34 E-value: 3.32e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  19 RFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKYKKGHRAGELRAVFNVLDQNGDG 98
Cdd:cd16224   8 NAEYDKEAFLGGEEDADEFAKLSPEEQQKRLKSIIKKIDTDSDGFLTEEELSSWIQQSFRHYALEDAKQQFPEYDKDGDG 87


                ....*.
gi 34014144  99 YITVDE 104
Cdd:cd16224  88 AVTWDE 93

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: 39.05 E-value: 3.74e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  11 AEFQAAFNRFDKNKDGHISVEELGDVMKQLGK--NLPEKDLK------ALISKLDTDGDGKISF----------EEFLTA 72
Cdd:cd16176  85 EEFMQTWRKYDADHSGFIEADELKSFLKDLLKkaNKPFDESKleeythTMLKMFDSNNDGKLGLtemarllpvqENFLLK 164

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 34014144  73 IEKYKKGHRagELRAVFNVLDQNGDGYITVDELKESLSKLGESLSQE 119
Cdd:cd16176 165 FQGVKMCGK--EFNKIFELYDQDGNGYIDENELDALLKDLCEKNKKD 209

EF-hand domain pair;

Pssm-ID: 404678 [Multi-domain] Cd Length: 54 Bit Score: 36.14 E-value: 4.46e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 34014144    60 GDGKISFEEFLTAIEKYKKGH-RAGELRAVFNVLDQNGDGYITVDELKESL 109
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDlSEDEVDILFREFDTDGDGYISFDEFCVLL 51

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: 4.68e-04

                          10        20
                  ....*....|....*....|....*...
gi 34014144    48 DLKALISKLDTDGDGKISFEEFLTAIEK 75
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKK 28

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: 37.61 E-value: 7.13e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  38 KQLGKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKYKkghRAGELRAVFNVLDQNGDGYITVDELKESLSKL-GESL 116
Cdd:cd16207  29 RRLHINCSESYLRELFDKADTDKKGYLNFEEFQEFVKLLK---RRKDIKAIFKQLTKPGSDGLTLEEFLKFLRDVqKEDV 105


                ....*.
gi 34014144 117 SQEELE 122
Cdd:cd16207 106 DRETWE 111

phosphatidylserine decarboxylase

Pssm-ID: 215520 [Multi-domain] Cd Length: 644 Bit Score: 38.30 E-value: 9.08e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 34014144   21 DKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEF--LTAIEKYK 77
Cdd:PLN02964 189 DYDEDGQLSFSEFSDLIKAFGNLVAANKKEELFKAADLNGDGVVTIDELaaLLALQQEQ 247

Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed calcium-activated neutral proteinase 12 (CANP 12), is a calpain large subunit mainly expressed in the cortex of the hair follicle. It may affect apoptosis regulation. CAPN12 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.

Pssm-ID: 320069 [Multi-domain] Cd Length: 169 Bit Score: 37.55 E-value: 1.07e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  12 EFQAAFNRFdKNKDGHISVEELGDVMKQL--------GKNLPEKDLKALISKLDTDGDGKISFEEFLTAIEKYKkghrag 83
Cdd:cd16194   1 ELEQLFQEL-AGEDEEINASELQKILSIAlerahtskPREFGLRTCRQLIQCFDHGQNGKLALEEFQQLWGYLL------ 73

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 34014144  84 ELRAVFNVLDQNGDGYITVDELKESLSKLG--------ESLSQEELEDMIRV 127
Cdd:cd16194  74 EWQAIFTKFDEDTSGTMDSYELRLALNAAGfhlnnqltETLTSRYRDSRLRV 125

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: 34.68 E-value: 1.08e-03

                          10        20
                  ....*....|....*....|....*....
gi 34014144    84 ELRAVFNVLDQNGDGYITVDELKESLSKL 112
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29

transaldolase;

Pssm-ID: 183426 [Multi-domain] Cd Length: 391 Bit Score: 37.79 E-value: 1.19e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 34014144   57 DTDGDGKISFEEFLTAiekykkghragelRAVFNVLDQNGDGYITVDELKESL 109
Cdd:PRK12309 344 DLDGDGFITREEWLGS-------------DAVFDALDLNHDGKITPEEMRAGL 383

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: 35.93 E-value: 1.36e-03

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 34014144  32 ELGDVMKQLGKnlpEKDLKALISKLDTDGDGKISFEEFLTAIEK 75
Cdd:cd00213  39 ELPNFLKNQKD---PEAVDKIMKDLDVNKDGKVDFQEFLVLIGK 79

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: 36.44 E-value: 1.50e-03

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 34014144  85 LRAVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVDQDGKVKYEEFV 142
Cdd:cd16202   2 LKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFV 59

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: 37.02 E-value: 1.54e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  14 QAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDtDGDGKISFEEFLTAIEKYKKghrageLRAVFNVLD 93
Cdd:cd15897  73 QEIFRTYDTDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYD-RGRGNIDFDDFIQCCVRLQR------LTDAFRRYD 145


                ....*....
gi 34014144  94 QNGDGYITV 102
Cdd:cd15897 146 KDQDGQIQV 154

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: 36.82 E-value: 1.80e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144   9 EVAEFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLdTDGDGKISFEEFLTAIEKYKKGHRagelraV 88
Cdd:cd16182  70 DLKKWQAIFKKFDTDRSGTLSSYELRKALESAGFHLSNKVLQALVLRY-ADSTGRITFEDFVSCLVRLKTAFE------T 142

                        90
                ....*....|..
gi 34014144  89 FNVLDQNGDGYI 100
Cdd:cd16182 143 FSALDKKNEGVI 154

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: 36.78 E-value: 2.30e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144   7 KEEVAEFqaaFNRFDKNKDGHISVEELGDVmkqlgknlpekdlkaliskLDTDgdgkisfEEFLTAIEKYKkgHRAGELR 86
Cdd:cd16177  45 GEKMKEF---MQKYDKNADGRIEMAELAQI-------------------LPTE-------ENFLLCFRQHV--GSSSEFM 93

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34014144  87 AVFNVLDQNGDGYITVDELKESLSKL--------GESLSQEELEDMIRVADVDQDGKVKYEEFVRL 144
Cdd:cd16177  94 EAWRKYDTDRSGYIEANELKGFLSDLlkkanrpyDEKKLQEYTQTILRMFDLNGDGKLGLSEMARL 159

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: 33.51 E-value: 2.94e-03

                           10        20
                   ....*....|....*....|....*....
gi 34014144     84 ELRAVFNVLDQNGDGYITVDELKESLSKL 112
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

EF hand;

Pssm-ID: 433035 [Multi-domain] Cd Length: 25 Bit Score: 33.45 E-value: 3.21e-03

                          10        20
                  ....*....|....*....|...
gi 34014144    85 LRAVFNVLDQNGDGYITVDELKE 107
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRR 23

EF hand;

Pssm-ID: 433035 [Multi-domain] Cd Length: 25 Bit Score: 33.45 E-value: 3.35e-03

                          10        20
                  ....*....|....*....|.
gi 34014144    49 LKALISKLDTDGDGKISFEEF 69
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEEL 21

EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein SMOC-1, SMOC-2, and similar proteins; SMOC proteins corresponds to a group matricellular proteins that are involved in direct or indirect modulation of growth factor signaling pathways and play diverse roles in physiological processes involving extensive tissue remodeling, migration, proliferation, and angiogenesis. They may mediate intercellular signaling and cell type-specific differentiation during gonad and reproductive tract development. SMOC-1 is localized in basement membranes. Its mutations have been found to be associated with individuals with Warrdenburg Anopthalmia Syndrome. SMOC-2 is ubiquitously expressed and is involved in angiogenesis and the regulation of cell cycle progression. It enhances the angiogenic effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). It has also been implicated in generalized vitiligo. SMOC proteins consist of a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain conserved only in SMOC proteins, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.

Pssm-ID: 320013 Cd Length: 104 Bit Score: 34.95 E-value: 3.77e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34014144   6 TKEEVAEFQaaFNRFDKNKDGHISVEELGDVMKQLGKNL-PEKDLKALISKLDTDGDGKISFEEFL 70
Cdd:cd16234  36 SEEQVLDWK--FSQLDKNKNGVLERKEWKPFKRLLKKAVkPKKCARKFPKYCDVNKDKKISLTEWL 99

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: 36.23 E-value: 4.19e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  13 FQAAFNRFDKNKDGHISVEELGDVMKQL----------GKNLPEKDLKALISKL----DTDGDGKISF----------EE 68
Cdd:cd16179   1 FMDVWNHYDTDGNGYIEGTELDGFLREFvssvnpedvgPEVVSETALEELKEEFmeayDENQDGRIDIrelaqllpteEN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  69 FLTAIEKYKKGHRAGELRAVFNVLDQNGDGYITVDELKESL------SKLGESLSQEEL----EDMIRVADVDQDGKVKY 138
Cdd:cd16179  81 FLLLFRRDNPLDSSVEFMKVWREYDKDNSGYIEADELKNFLkhllkeAKRDNDVSEDKLieytDTILQLFDRNKDGKLQL 160


                ....*.
gi 34014144 139 EEFVRL 144
Cdd:cd16179 161 SEMARL 166

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: 35.84 E-value: 4.82e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  12 EFQAAFNRFDKNKDGHISVEEL----GDVMKQLGKNLPEKDLK----ALISKLDTDGDGKISFEE------------FLT 71
Cdd:cd16178  93 EFMRIWRKYDADSSGYISAAELknflRDLFLQHKKVITEDKLDeytdTMMKIFDKNKDGRLDLNDmarilalqenflLQF 172

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 34014144  72 AIEKYKKGHRAGELRAVFNVLDQNGDGYITVDELKESLSKLGE----SLSQEELED----MIRVADVDQDGKVKYEE 140
Cdd:cd16178 173 KMDAMSEEERKRDFEKIFAHYDVSKTGALEGPEVDGFVKDMMElvkpSISGVQLDKfkeiILNHCDVNKDGKIQKSE 249

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: 33.86 E-value: 5.40e-03

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 34014144  13 FQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALiskldtdgDGKISFEEFL 70
Cdd:cd22949   5 FREAFILFDRDGDGELTMYEAVLAMRSCGIPLTNDEKDAL--------PASMNWDQFE 54

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: 35.26 E-value: 5.55e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  50 KALISKLDTDGDGKISFEEF---LTAIEKYKKghragelraVFNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMI- 125
Cdd:cd16199  46 KIMVDMLDSDGSGKLGLKEFyilWTKIQKYQK---------IYREIDVDRSGTMNSYEMRKALEEAGFKLPCQLHQVIVa 116

                        90
                ....*....|....*...
gi 34014144 126 RVADVDQDgkVKYEEFVR 143
Cdd:cd16199 117 RFADDDLI--IDFDNFVR 132

EF-hand, extracellular calcium-binding (EC) motif, found in testicans; Testicans are nervous system-expressed proteoglycans that play important roles in the regulation of protease activity, as well as in the determination of age at menarche. Testican-1 (TICN1, also termed protein SPOCK) is a secreted chimeric proteoglycan that is highly expressed in brain and carries both chondroitin and heparan sulfate glycosaminoglycan side chains. It has been implicated in autoimmune disease. It also acts as a regulator of bone morphogenetic protein (BMP) signaling and show critical functions in the nervous system. Testican-2 (TICN2, also termed protein SPOCK2) is an extracellular heparan sulphate proteoglycan highly expressed in brain. It may play regulatory roles in the development of the central nervous system. It also participates in diverse steps of neurogenesis. TICN1, but not TICN2, inhibits cathepsin L. TICN1 also inhibits attachment and neurite outgrowth in cultures of N2A neuroblastoma cells, While TICN2 is able to inhibit neurite outgrowth from primary cerebellar cells. Testicans contain an N-terminal signal peptide, a testican-specific domain followed by a follistatin-like (FS) domain, an extracellular calcium-binding (EC) domain including a pair of EF hands, a thyroglobulin-like domain (TY), and a C-terminal region with two putative glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr orTyr in the +Y position of EF hand 2 in testican-2 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ with low affinity. The substitution of a ligating Asp residue by Phe or Tyr in the +Y position of EF-hand 2 in testicans could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.

Pssm-ID: 320011 Cd Length: 108 Bit Score: 34.27 E-value: 6.05e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 34014144  42 KNLPE--KDLKALISKLDTDGDGKISFEEfLTAIE--KYKKGhrageLRAVFNVLDQNGDGYITVDE 104
Cdd:cd16232  39 SHLPEckPSVGWMFNQLDTNNDLHLSQSE-LYDLEldKYEPC-----IKPFLDSCDRNKDGKISSDE 99

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: 6.49e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  50 KALISKLDTDGDGKISFEEF---LTAIEKYKKghragelraVFNVLDQNGDGYITVDELKESLSKLGESLSQeELEDMIR 126
Cdd:cd16189  46 RNMVNLLDKDGSGKLGLVEFqilWTKIQKYLK---------IYKKFDTDGSGTMSSYEMRLALEEAGFKLNN-QLHQVLV 115

                        90
                ....*....|....*..
gi 34014144 127 VADVDQDGKVKYEEFVR 143
Cdd:cd16189 116 ARYADQELTIDFDNFVR 132

Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed calcium-activated neutral proteinase 12 (CANP 12), is a calpain large subunit mainly expressed in the cortex of the hair follicle. It may affect apoptosis regulation. CAPN12 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.

Pssm-ID: 320069 [Multi-domain] Cd Length: 169 Bit Score: 35.24 E-value: 6.57e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144   8 EEVAEFQAAFNRFDKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDgKISFEEFLTAIekykkghraGELRA 87
Cdd:cd16194  70 GYLLEWQAIFTKFDEDTSGTMDSYELRLALNAAGFHLNNQLTETLTSRYRDSRL-RVDFESFLSCL---------AHLTC 139

                        90
                ....*....|....*...
gi 34014144  88 VF---NVLDQNGDGYITV 102
Cdd:cd16194 140 IFcqcSQHDDGGEGVICL 157

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: 34.00 E-value: 6.83e-03

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 34014144  96 GDGYITVDELKESLSK-----LGESLSQEELEDMIRVADVDQDGKVKYEEFVRL 144
Cdd:cd00213  23 DKDTLSKKELKELLETelpnfLKNQKDPEAVDKIMKDLDVNKDGKVDFQEFLVL 76

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: 35.10 E-value: 9.25e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34014144  57 DTDGDGKISFEEFLTAIEKYKKGHRAGELRAV-----FNVLDQNGDGYITVDELKESLSKLGESLSQEELEDMIRVADVD 131
Cdd:cd16224 171 DKDGDGFISLEEFLGDYRKDPTANEDPEWIIVekdrfVNDYDKDNDGKLDPQELLPWVVPNNYGIAQEEALHLIDEMDLN 250


                ....*....
gi 34014144 132 QDGKVKYEE 140
Cdd:cd16224 251 GDGRLSEEE 259

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: 34.97 E-value: 9.72e-03

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 34014144  21 DKNKDGHISVEELGDVMKQLGKNLPEKDLKALISKLDTDGDGKISFEEFL 70
Cdd:cd16225 222 DLNHDGKVTKEELEEYMDPRNERHALNEAKQLIAVADENKDGKLSLEEIL 271