S-100/ICaBP type calcium binding domain; The S-100 domain is a subfamily of the EF-hand calcium binding proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 560791      10 TERCIESLIAVFQKYAGKDGYNYTLSKTEFLSFMNTELAAFTKNQ 54
Cdd:pfam01023   1 LERAIETIIDVFHKYAGKEGDKDTLSKKELKELLEKELPNFLKNQ 45

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 560791       60 LDRMMKKLDTNSDGQLDFSEFLNLIGGL 87
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

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 560791     8 TETERCIESLIAVFQKYAGKDGYNYTLSKTEFLSFMNTELAAFTKNQKDPGVLDRMMKKLDTNSDGQLDFSEFLNLIGGL 87
Cdd:cd00213   1 SELEKAIETIIDVFHKYSGKEGDKDTLSKKELKELLETELPNFLKNQKDPEAVDKIMKDLDVNKDGKVDFQEFLVLIGKL 80

                ....*...
gi 560791    88 AMACHDSF 95
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 560791     8 TETERCIESLIAVFQKYAGKDGYNYTLSKTEFLSFMNTELAAFTKNQKDPGVLDRMMKKLDTNSDGQLDFSEFLNLIGGL 87
Cdd:cd05030   1 TELEKAIETIINVFHQYSVRKGHPDTLYKKEFKQLVEKELPNFLKKEKNQKAIDKIFEDLDTNQDGQLSFEEFLVLVIKV 80

                ....*.
gi 560791    88 AMACHD 93
Cdd:cd05030  81 GVAAHE 86

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 560791     7 PTETERCIESLIAVFQKYAGKDGYNYTLSKTEFLSFMNTELAAFTKNQKDPGVLDRMMKKLDTNSDGQLDFSEFLNLIGG 86
Cdd:cd05026   2 PTQLEGAMDTLIRIFHNYSGKEGDRYKLSKGELKELLQRELTDFLSSQKDPMLVDKIMNDLDSNKDNEVDFNEFVVLVAA 81

                ....*....
gi 560791    87 LAMACHDSF 95
Cdd:cd05026  82 LTVACNDFF 90

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 560791     8 TETERCIESLIAVFQKYAGKDGYnytLSKTEFLSFMNTELAAFTKNQKDPGVLDRMMKKLDTNSDGQLDFSEFLNLIGGL 87
Cdd:cd05024   1 SELEHSMEKMMLTFHKFAGEKNY---LNRDDLQKLMEKEFSEFLKNQNDPMAVDKIMKDLDDCRDGKVGFQSFFSLIAGL 77

                        90
                ....*....|
gi 560791    88 AMACHDSFLK 97
Cdd:cd05024  78 LIACNDYYVK 87

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 560791     8 TETERCIESLIAVFQKYAGKDGYNyTLSKTEFLSFMNTELAAFTKnqkDPGVLDRMMKKLDTNSDGQLDFSEFLNLIGGL 87
Cdd:cd05022   1 TELEKAIETLVSNFHKASVKGGKE-SLTASEFQELLTQQLPHLLK---DVEGLEEKMKNLDVNQDSKLSFEEFWELIGEL 76

                ....*
gi 560791    88 AMACH 92
Cdd:cd05022  77 AKAVK 81

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 560791    27 KDGyNYTLSKTEFLSFMNTELAAFTKNQkdpgvLDRMMKKLDTNSDGQLDFSEFLNLI 84
Cdd:cd00051  11 KDG-DGTISADELKAALKSLGEGLSEEE-----IDEMIREVDKDGDGKIDFEEFLELM 62

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 560791    15 ESLIAVFQKY-AGKDGYnytLSKTEFLSFMntelaafTKNQKDPGVLDRMMKKLDTNSDGQLDFSEFLNLI 84
Cdd:COG5126  69 PFARAAFDLLdTDGDGK---ISADEFRRLL-------TALGVSEEEADELFARLDTDGDGKISFEEFVAAV 129

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 560791       60 LDRMMKKLDTNSDGQLDFSEFLNLIGGL 87
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 560791      60 LDRMMKKLDTNSDGQLDFSEFLNLI 84
Cdd:pfam00036   2 LKEIFRLFDKDGDGKIDFEEFKELL 26

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 560791    27 KDGynyTLSKTEFLSFMNTELAAFTKNQkdpgVLDRMMKKLDTNSDGQLDFSEFL 81
Cdd:cd16226 132 GDG---KLTKEEFTAFLHPEEFPHMRDI----VVQETLEDIDKNKDGFISLEEYI 179