calmodulin; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 564373424  38 FDPGSTGYISTGKFRSLLESHSSKLDPHKKEVLLALADSHADGQICYQDFVNLMSNK 94
Cdd:PTZ00184  93 FDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMMMSK 149

Membrane-associated serine protease, rhomboid family [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564373424 155 PWFMITITLLEVALFLYNGVLLDQFVlqvthprylkNSLVYHPQ--LRAQAWRYVTYIFMHAGVEQLGLNVALQLLVGVP 232
Cdd:COG0705    3 PPVTLALIALNVLVFLLQLLLGGELL----------NWLALVPArlLLGELWRLLTSMFLHGGFLHLLFNMLALWVFGPL 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564373424 233 LEMVHGATRIGLVYVAGVVAGSLAVSVADMT--APVVGSSGGVYALVSAHLA-NIVMNWSGMKCQFKLLRMAVALICMSM 309
Cdd:COG0705   73 LERRLGSKRFLLLYLLSGLGGGLLQLLFSPGsgYPLVGASGAIFGLLGALLVlGPRRRVLLLFIPIPALLFLLVWLLLGL 152

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 564373424 310 EFGRAVWlrfhpsayppcPHPSFVAHLGGVAVGITLGVVVLRNYEQR 356
Cdd:COG0705  153 LFGLLGG-----------GGIAWEAHLGGLLAGLLLALLLRKLRRRR 188

calmodulin; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 564373424  38 FDPGSTGYISTGKFRSLLESHSSKLDPHKKEVLLALADSHADGQICYQDFVNLMSNK 94
Cdd:PTZ00184  93 FDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMMMSK 149

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 564373424  38 FDPGSTGYISTGKFRSLLESHSSKLDPHkkeVLLALAD--SHADGQICYQDFVNLM 91
Cdd:cd16196   80 FDTDGSGSFSSFELRNALNSAGFRLSNA---TLNALVLrySNKDGRISFDDFIMCA 132

Membrane-associated serine protease, rhomboid family [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564373424 155 PWFMITITLLEVALFLYNGVLLDQFVlqvthprylkNSLVYHPQ--LRAQAWRYVTYIFMHAGVEQLGLNVALQLLVGVP 232
Cdd:COG0705    3 PPVTLALIALNVLVFLLQLLLGGELL----------NWLALVPArlLLGELWRLLTSMFLHGGFLHLLFNMLALWVFGPL 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564373424 233 LEMVHGATRIGLVYVAGVVAGSLAVSVADMT--APVVGSSGGVYALVSAHLA-NIVMNWSGMKCQFKLLRMAVALICMSM 309
Cdd:COG0705   73 LERRLGSKRFLLLYLLSGLGGGLLQLLFSPGsgYPLVGASGAIFGLLGALLVlGPRRRVLLLFIPIPALLFLLVWLLLGL 152

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 564373424 310 EFGRAVWlrfhpsayppcPHPSFVAHLGGVAVGITLGVVVLRNYEQR 356
Cdd:COG0705  153 LFGLLGG-----------GGIAWEAHLGGLLAGLLLALLLRKLRRRR 188

calmodulin; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 564373424  38 FDPGSTGYISTGKFRSLLESHSSKLDPHKKEVLLALADSHADGQICYQDFVNLMSNK 94
Cdd:PTZ00184  93 FDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMMMSK 149

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 564373424  38 FDPGSTGYISTGKFRSLLESHSSKLDPHkkeVLLALAD--SHADGQICYQDFVNLM 91
Cdd:cd16196   80 FDTDGSGSFSSFELRNALNSAGFRLSNA---TLNALVLrySNKDGRISFDDFIMCA 132

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 564373424  41 GSTGYISTGKFRSLLESH-----SSKLDPHKKEVLLALADSHADGQICYQDFVNLM 91
Cdd:cd00213   22 GDKDTLSKKELKELLETElpnflKNQKDPEAVDKIMKDLDVNKDGKVDFQEFLVLI 77