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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421719  1 MPTQLEMAMDTMIRIFHRYSGKERKRFKLSKGELKLLLQRELTEFLSCQKETQLVDKIVQDLDANKDNEVDFNEFVVMVA 80
Cdd:cd05026    1 MPTQLEGAMDTLIRIFHNYSGKEGDRYKLSKGELKELLQRELTDFLSSQKDPMLVDKIMNDLDSNKDNEVDFNEFVVLVA 80

                         90
                 ....*....|...
gi 1139421719 81 ALTVACNDYFVEQ 93
Cdd:cd05026   81 ALTVACNDFFQEQ 93

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421719  1 MPTQLEMAMDTMIRIFHRYSGKERKRFKLSKGELKLLLQRELTEFLSCQKETQLVDKIVQDLDANKDNEVDFNEFVVMVA 80
Cdd:cd05026    1 MPTQLEGAMDTLIRIFHNYSGKEGDRYKLSKGELKELLQRELTDFLSSQKDPMLVDKIMNDLDSNKDNEVDFNEFVVLVA 80

                         90
                 ....*....|...
gi 1139421719 81 ALTVACNDYFVEQ 93
Cdd:cd05026   81 ALTVACNDFFQEQ 93

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421719  1 MPTQLEMAMDTMIRIFHRYSGKERKRFKLSKGELKLLLQRELTEFLSCQKETQLVDKIVQDLDANKDNEVDFNEFVVMVA 80
Cdd:cd05026    1 MPTQLEGAMDTLIRIFHNYSGKEGDRYKLSKGELKELLQRELTDFLSSQKDPMLVDKIMNDLDSNKDNEVDFNEFVVLVA 80

                         90
                 ....*....|...
gi 1139421719 81 ALTVACNDYFVEQ 93
Cdd:cd05026   81 ALTVACNDFFQEQ 93

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421719  3 TQLEMAMDTMIRIFHRYSGKERKRFKLSKGELKLLLQRELTEFLSCQKETQLVDKIVQDLDANKDNEVDFNEFVVMVAAL 82
Cdd:cd00213    1 SELEKAIETIIDVFHKYSGKEGDKDTLSKKELKELLETELPNFLKNQKDPEAVDKIMKDLDVNKDGKVDFQEFLVLIGKL 80

                 ....*...
gi 1139421719 83 TVACNDYF 90
Cdd:cd00213   81 AVACHEFF 88

Calgranulins: S-100 domain found in proteins belonging to the Calgranulin subgroup of the S100 family of EF-hand calcium-modulated proteins, including S100A8, S100A9, and S100A12 . Note that the S-100 hierarchy, to which this Calgranulin group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. These proteins are expressed mainly in granulocytes, and are involved in inflammation, allergy, and neuritogenesis, as well as in host-parasite response. Calgranulins are modulated not only by calcium, but also by other metals such as zinc and copper. Structural data suggested that calgranulins may exist in multiple structural forms, homodimers, as well as hetero-oligomers. For example, the S100A8/S100A9 complex called calprotectin plays important roles in the regulation of inflammatory processes, wound repair, and regulating zinc-dependent enzymes as well as microbial growth.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421719  3 TQLEMAMDTMIRIFHRYSGKERKRFKLSKGELKLLLQRELTEFLSCQKETQLVDKIVQDLDANKDNEVDFNEFVVMVAAL 82
Cdd:cd05030    1 TELEKAIETIINVFHQYSVRKGHPDTLYKKEFKQLVEKELPNFLKKEKNQKAIDKIFEDLDTNQDGQLSFEEFLVLVIKV 80

                 ....*.
gi 1139421719 83 TVACND 88
Cdd:cd05030   81 GVAAHE 86

S-100A10: A subgroup of the 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-100A10 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421719  3 TQLEMAMDTMIRIFHRYSGKERKrfkLSKGELKLLLQRELTEFLSCQKETQLVDKIVQDLDANKDNEVDFNEFVVMVAAL 82
Cdd:cd05024    1 SELEHSMEKMMLTFHKFAGEKNY---LNRDDLQKLMEKEFSEFLKNQNDPMAVDKIMKDLDDCRDGKVGFQSFFSLIAGL 77

                         90
                 ....*....|....
gi 1139421719 83 TVACNDYFVEQLKK 96
Cdd:cd05024   78 LIACNDYYVKHMKQ 91

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421719  1 MPTQLEMAMDTMIRIFHRYSGKERKRFKLSKGELKLLLQRELTefLSCQKETQLVDKIVQDLDANKDNEVDFNEFVVMVA 80
Cdd:cd05029    1 MASPLDQAIGLLVAIFHKYSGREGDKNTLSKKELKELIQKELT--IGSKLQDAEIAKLMEDLDRNKDQEVNFQEYVTFLG 78

                 ....*...
gi 1139421719 81 ALTVACND 88
Cdd:cd05029   79 ALALIYNE 86

S-100A13: S-100A13 domain found in proteins similar to S100A13. S100A13 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-100A13 group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. S100A13 is involved in the cellular export of interleukin-1 (IL-1) and of fibroblast growth factor-1 (FGF-1), which plays an important role in angiogenesis and tissue regeneration. Export is based on the CuII-dependent formation of multiprotein complexes containing the S100A13 protein. Assembly of these complexes occurs near the inner surface of the plasma membrane. Binding of two Ca(II) ions per monomer triggers key conformational changes leading to the creation of two identical and symmetrical Cu(II)-binding sites on the surface of the protein, close to the interface between the two monomers. These Cu(II)-binding sites are unique among the S100 proteins, which are reported to bind Cu(II) or Zn(II) ions in addition to Ca(II) ions. In addition, the three-dimensional structure of S100A13 differs significantly from those of other S100 proteins; the hydrophobic pocket that largely contributes to protein-protein interactions in other S100 proteins is absent in S100A13. The structure of S100A13 contains a large patch of negatively charged residues flanked by dense cationic clusters, formed mostly from positively charged residues from the C-terminal end, which plays major role in binding FGF-1.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421719  3 TQLEMAMDTMIRIFHRYSGKERKRfKLSKGELKLLLQRELTEFLscqKETQLVDKIVQDLDANKDNEVDFNEFVVMVAAL 82
Cdd:cd05022    1 TELEKAIETLVSNFHKASVKGGKE-SLTASEFQELLTQQLPHLL---KDVEGLEEKMKNLDVNQDSKLSFEEFWELIGEL 76

                 ...
gi 1139421719 83 TVA 85
Cdd:cd05022   77 AKA 79

EF-hand domain pair;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1139421719  9 MDTMIRIFHRYsgKERKRFKLSKGELKLLLQRELTEFLSCQKEtqlVDKIVQDLDANKDNEVDFNEFVVMV 79
Cdd:pfam13499  1 EEKLKEAFKLL--DSDGDGYLDVEELKKLLRKLEEGEPLSDEE---VEELFKEFDLDKDGRISFEEFLELY 66