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.

                       10        20        30        40        50        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27806285 13 IFEKYAAKEGDPNQLSKEELKLLLQTEFPSLLKG---PSTLDELFEELDKNGDGEVSFEEFQVLVKKISQ 79
Cdd:cd00213 13 VFHKYSGKEGDKDTLSKKELKELLETELPNFLKNqkdPEAVDKIMKDLDVNKDGKVDFQEFLVLIGKLAV 82

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        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27806285 13 IFEKYAAKEGDPNQLSKEELKLLLQTEFPSLLKG---PSTLDELFEELDKNGDGEVSFEEFQVLVKKISQ 79
Cdd:cd00213 13 VFHKYSGKEGDKDTLSKKELKELLETELPNFLKNqkdPEAVDKIMKDLDVNKDGKVDFQEFLVLIGKLAV 82

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 27806285  38 TEFPSLLKG----PSTLDELFEELDKNGDGEVSFEEFQVLVKK 76
Cdd:COG5126  89 DEFRRLLTAlgvsEEEADELFARLDTDGDGKISFEEFVAAVRD 131

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 27806285   37 QTEFPSLLKGPS------TLDELFEELDKNGDGEVSFEEF 70
Cdd:NF041410  46 QDELSSALSSKSddgsliDLSELFSDLDSDGDGSLSSDEL 85

XopAW family type III secretion system calcium-binding effector;

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 27806285   37 QTEFPSLLKGP-STLD--ELFEELDKNGDGEVSFEEFQ 71
Cdd:NF041410 122 SDELSAGLTSAgSSADssQLFSALDSDGDGSVSSDELA 159

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        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27806285 13 IFEKYAAKEGDPNQLSKEELKLLLQTEFPSLLKG---PSTLDELFEELDKNGDGEVSFEEFQVLVKKISQ 79
Cdd:cd00213 13 VFHKYSGKEGDKDTLSKKELKELLETELPNFLKNqkdPEAVDKIMKDLDVNKDGKVDFQEFLVLIGKLAV 82

S-100A10_like: S-100A10 domain found in proteins similar to S100A10. S100A10 is a member of the S100 family of EF-hand superfamily of calcium-binding proteins. Note that the S-100 hierarchy, to which this S-100A1_like group belongs, 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. A unique feature of S100A10 is that it contains mutation in both of the calcium binding sites, making it calcium insensitive. S100A10 has been detected in brain, heart, gastrointestinal tract, kidney, liver, lung, spleen, testes, epidermis, aorta, and thymus. Structural data supports the homo- and hetero-dimeric as well as hetero-tetrameric nature of the protein. S100A10 has multiple binding partners in its calcium free state and is therefore involved in many diverse biological functions.

                       10        20        30        40        50        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27806285  5 KSPEELKGIFEKYAAKEGDPNQLSKEELKLLLQTEFPSLLKG---PSTLDELFEELDKNGDGEVSFEEFQVLV 74
Cdd:cd05031  5 HAMESLILTFHRYAGKDGDKNTLSRKELKKLMEKELSEFLKNqkdPMAVDKIMKDLDQNRDGKVNFEEFVSLV 77

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.

                          10        20
                  ....*....|....*....|....*...
gi 27806285    50 LDELFEELDKNGDGEVSFEEFQVLVKKI 77
Cdd:smart00054  2 LKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

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.

                         10        20
                 ....*....|....*....|....*...
gi 27806285   50 LDELFEELDKNGDGEVSFEEFQVLVKKI 77
Cdd:pfam00036  2 LKEIFRLFDKDGDGKIDFEEFKELLKKL 29

S-100B: S-100B domain found in proteins similar to S100B. S100B is a calcium-binding protein belonging to a large S100 vertebrate-specific protein family within the EF-hand superfamily of calcium-binding proteins. Note that the S-100 hierarchy, to which this S-100B group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. S100B is most abundant in glial cells of the central nervous system, predominately in astrocytes. S100B is involved in signal transduction via the inhibition of protein phoshorylation, regulation of enzyme activity and by affecting the calcium homeostasis. Upon calcium binding the S100B homodimer changes conformation to expose a hydrophobic cleft, which represents the interaction site of S100B with its more than 20 known target proteins. These target proteins include several cellular architecture proteins such as tubulin and GFAP; S100B can inhibit polymerization of these oligomeric molecules. Furthermore, S100B inhibits the phosphorylation of multiple kinase substrates including the Alzheimer protein tau and neuromodulin (GAP-43) through a calcium-sensitive interaction with the protein substrates.

                       10        20        30        40        50        60
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27806285 13 IFEKYAAKEGDPNQLSKEELKLLLQTEFPSLL---KGPSTLDELFEELDKNGDGEVSFEEFQVLVKKIS 78
Cdd:cd05027 13 VFHQYSGREGDKHKLKKSELKELINNELSHFLeeiKEQEVVDKVMETLDSDGDGECDFQEFMAFVAMVT 81

S-100Z: S-100Z domain found in proteins similar to S100Z. S100Z is a member of the S100 domain family within the EF-hand Ca2+-binding proteins superfamily. Note that the S-100 hierarchy, to which this S-100Z group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately.S100 proteins exhibit unique patterns of tissue- and cell type-specific expression and have been implicated in the Ca2+-dependent regulation of diverse physiological processes, including cell cycle regulation, differentiation, growth, and metabolic control. S100Z is normally expressed in various tissues, with its highest level of expression being in spleen and leukocytes. The function of S100Z remains unclear. Preliminary structural data suggests that S100Z is homodimer, however a heterodimer with S100P has been reported. S100Z is capable of binding calcium ions. When calcium binds to S110Z, the protein experiences a conformational change, which exposes hydrophobic surfaces on the protein. In comparison with their normal tissue counterparts, S100Z gene expression appears to be deregulated in some tumor tissues.

                       10        20        30        40        50        60
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27806285 13 IFEKYAAKEGDPNQLSKEELKLLLQ---TEFPSLLKGPSTLDELFEELDKNGDGEVSFEEFQVLVKKIS 78
Cdd:cd05026 15 IFHNYSGKEGDRYKLSKGELKELLQrelTDFLSSQKDPMLVDKIMNDLDSNKDNEVDFNEFVVLVAALT 83

S-100A6: S-100A6 domain found in proteins similar to S100A6. S100A6 is a member of the S100 domain family within EF-hand Ca2+-binding proteins superfamily. Note that the S-100 hierarchy, to which this S-100A6 group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. S100 proteins exhibit unique patterns of tissue- and cell type-specific expression and have been implicated in the Ca2+-dependent regulation of diverse physiological processes, including cell cycle regulation, differentiation, growth, and metabolic control . S100A6 is normally expressed in the G1 phase of the cell cycle in neuronal cells. The function of S100A6 remains unclear, but evidence suggests that it is involved in cell cycle regulation and exocytosis. S100A6 may also be involved in tumorigenesis; the protein is overexpressed in several tumors. Ca2+ binding to S100A6 leads to a conformational change in the protein, which exposes a hydrophobic surface for interaction with target proteins. Several such proteins have been identified: glyceraldehyde-3-phosphate dehydrogenase , annexins 2, 6 and 11 and Calcyclin-Binding Protein (CacyBP).

                       10        20        30        40        50        60
               ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27806285 10 LKGIFEKYAAKEGDPNQLSKEELKLLLQTEfpsLLKGPSTLD----ELFEELDKNGDGEVSFEEF 70
Cdd:cd05029 12 LVAIFHKYSGREGDKNTLSKKELKELIQKE---LTIGSKLQDaeiaKLMEDLDRNKDQEVNFQEY 73

EF-hand domain pair;

                         10        20
                 ....*....|....*....|....*.
gi 27806285   50 LDELFEELDKNGDGEVSFEEFQVLVK 75
Cdd:pfam13499 42 VEELFKEFDLDKDGRISFEEFLELYS 67

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

                        10        20
                ....*....|....*....|....*....
gi 27806285  49 TLDELFEELDKNGDGEVSFEEFQVLVKKI 77
Cdd:COG5126  70 FARAAFDLLDTDGDGKISADEFRRLLTAL 98

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 27806285   37 QTEFPSLLKGPS------TLDELFEELDKNGDGEVSFEEF 70
Cdd:NF041410  46 QDELSSALSSKSddgsliDLSELFSDLDSDGDGSLSSDEL 85

XopAW family type III secretion system calcium-binding effector;

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 27806285   37 QTEFPSLLKGP-STLD--ELFEELDKNGDGEVSFEEFQ 71
Cdd:NF041410 122 SDELSAGLTSAgSSADssQLFSALDSDGDGSVSSDELA 159