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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
3I5I_B       16 QELKEAFTMIDQDRDGFIGMEDLKDMFSSLGRVPPDDELNAMlkecPGQLNFTAFLTLFGEKVSGTDP 83
Cdd:cd22949   3 EKFREAFILFDRDGDGELTMYEAVLAMRSCGIPLTNDEKDAL----PASMNWDQFENWAKKKLAYSDP 66

EF-hand domain;

                          10        20        30
                  ....*....|....*....|....*....|
3I5I_B         17 ELKEAFTMIDQDRDGFIGMEDLKDMFSSLG 46
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30

centrin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3I5I_B         7 RVKLSQRQMQELKEAFTMIDQDRDGFIGMEDLKDMFSSLGRVPPDDELNAML----KECPGQLNFTAFLTLFGEKVSGTD 82
Cdd:PTZ00183   8 RPGLTEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIadvdKDGSGKIDFEEFLDIMTKKLGERD 87

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
3I5I_B        83 PEDALRNAFSMFDEDGQGFIPEDYLKDLLENMGDNFSKEEIKN 125
Cdd:PTZ00183  88 PREEILKAFRLFDDDKTGKISLKNLKRVAKELGETITDEELQE 130

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3I5I_B       14 QMQELKEAFTMIDQDRDGFIGMEDLKDMFSSLgrvpPDDELNAMLKECPGQLNFTAFLTlFGEKVSGTDPEDALRNAFSM 93
Cdd:COG5126   3 QRRKLDRRFDLLDADGDGVLERDDFEALFRRL----WATLFSEADTDGDGRISREEFVA-GMESLFEATVEPFARAAFDL 77

                        90       100
                ....*....|....*....|..
3I5I_B       94 FDEDGQGFIPEDYLKDLLENMG 115
Cdd:COG5126  78 LDTDGDGKISADEFRRLLTALG 99

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
3I5I_B        8 VKLSQRQMQELKEAFTMIDQDRDGFIGMEDLKDM---FSSLGRVPPDDELNAML----KECPGQLNFTAFLTL 73
Cdd:cd16251  26 VGLKQKSEDQIKKVFQILDKDKSGFIEEEELKYIlkgFSIAGRDLTDEETKALLaagdTDGDGKIGVEEFATL 98

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3I5I_B       17 ELKEAFTMIDQDRDGFIGMEDLKDMFSSLGRVPPDDE-LNAML----KECPGQLNFTAFLTLFGEKvsgtdpeDALRNAF 91
Cdd:cd16180   1 ELRRIFQAVDRDRSGRISAKELQRALSNGDWTPFSIEtVRLMInmfdRDRSGTINFDEFVGLWKYI-------QDWRRLF 73

                        90       100
                ....*....|....*....|....*...
3I5I_B       92 SMFDEDGQGFIPEDYLKDLLENMGDNFS 119
Cdd:cd16180  74 RRFDRDRSGSIDFNELQNALSSFGYRLS 101

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).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3I5I_B       17 ELKEAFTMIDQDRDGFIGMEDLKDMFSSLGRVPPDDELNAMLK----ECPGQLNFTAFLTLFgEKVSgtdpedALRNAFS 92
Cdd:cd16185   1 ELRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRmfdrDGNGTIDFEEFAALH-QFLS------NMQNGFE 73

                        90
                ....*....|
3I5I_B       93 MFDEDGQGFI 102
Cdd:cd16185  74 QRDTSRSGRL 83

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).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
3I5I_B       10 LSQRQMQELKEAFTMIDQDRDGFIGMEDLK---DMFSSLGRVPPDDELNAMLK 59
Cdd:cd16255  28 LSKKSADDVKKVFEIIDQDKSGFIEEEELKlflQNFSSGARELTDAETKAFLK 80

centrin; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
3I5I_B        82 DPEDALRNAFSMFDEDGQGFIPEDYLKDLLENMGDNFSKEEIKNVWKD 129
Cdd:PTZ00183  14 DQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIAD 61

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).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
3I5I_B       51 DDELNAMLKEC--PGQLNFTAFLTLFGekVSGTDPEDaLRNAFSMFDEDGQGFIPEDYLKDLLEN 113
Cdd:cd16255   1 AADIAAALSQCqaADSFNFKKFFATSG--LSKKSADD-VKKVFEIIDQDKSGFIEEEELKLFLQN 62

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
3I5I_B        8 VKLSQRQMQELKEAFTMIDQDRDGFIGMEDLKDM---FSSLGRVPPDDELNAML----KECPGQLNFTAFLTLFGE 76
Cdd:cd16254  26 VGLKKKSADDVKKVFHILDKDKSGFIEEDELKFVlkgFSPDGRDLSDKETKALLaagdKDGDGKIGIDEFATLVAE 101

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3I5I_B        3 EAPRRVKLSQRQMQELKEAFTMIDQDRDGFIGMEDLKDMFSSLGRVPP-----DDELNAMLK----ECPGQLNFTAFLTL 73
Cdd:cd16252  24 EYMQKFQTSEQQEEAIRKAFQMLDKDKSGFIEWNEIKYILSTVPSSMPvaplsDEEAEAMIQaadtDGDGRIDFQEFSDM 103