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 7657532   1 MACPLDQAIGLLVAIFHKYSGREGDKHTLSKKELKELIQKELTIGSKLQDAEIARLMEDLDRNKDQEVNFQEYVTFLGAL 80
Cdd:cd05029  1 MASPLDQAIGLLVAIFHKYSGREGDKNTLSKKELKELIQKELTIGSKLQDAEIAKLMEDLDRNKDQEVNFQEYVTFLGAL 80

               ....*...
gi 7657532  81 ALIYNEAL 88
Cdd:cd05029 81 ALIYNEAL 88

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 7657532   1 MACPLDQAIGLLVAIFHKYSGREGDKHTLSKKELKELIQKELTIGSKLQDAEIARLMEDLDRNKDQEVNFQEYVTFLGAL 80
Cdd:cd05029  1 MASPLDQAIGLLVAIFHKYSGREGDKNTLSKKELKELIQKELTIGSKLQDAEIAKLMEDLDRNKDQEVNFQEYVTFLGAL 80

               ....*...
gi 7657532  81 ALIYNEAL 88
Cdd:cd05029 81 ALIYNEAL 88

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 7657532     52 EIARLMEDLDRNKDQEVNFQEYVTFLGAL 80
Cdd:smart00054  1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

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 7657532   1 MACPLDQAIGLLVAIFHKYSGREGDKHTLSKKELKELIQKELTIGSKLQDAEIARLMEDLDRNKDQEVNFQEYVTFLGAL 80
Cdd:cd05029  1 MASPLDQAIGLLVAIFHKYSGREGDKNTLSKKELKELIQKELTIGSKLQDAEIAKLMEDLDRNKDQEVNFQEYVTFLGAL 80

               ....*...
gi 7657532  81 ALIYNEAL 88
Cdd:cd05029 81 ALIYNEAL 88

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 7657532   1 MACPLDQAIGLLVAIFHKYSGREGDKHTLSKKELKELIQKELT--IGSKLQDAEIARLMEDLDRNKDQEVNFQEYVTFLG 78
Cdd:cd05026  1 MPTQLEGAMDTLIRIFHNYSGKEGDRYKLSKGELKELLQRELTdfLSSQKDPMLVDKIMNDLDSNKDNEVDFNEFVVLVA 80

               ....*...
gi 7657532  79 ALALIYNE 86
Cdd:cd05026 81 ALTVACND 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
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 7657532   5 LDQAIGLLVAIFHKYSGREGDKHTLSKKELKELIQKEL--TIGSKLQDAEIARLMEDLDRNKDQEVNFQEYV 74
Cdd:cd05030  3 LEKAIETIINVFHQYSVRKGHPDTLYKKEFKQLVEKELpnFLKKEKNQKAIDKIFEDLDTNQDGQLSFEEFL 74

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        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7657532   5 LDQAIGLLVAIFHKYSGREGDKHTLSKKELKELIQKELT--IGSKLQDAEIARLMEDLDRNKDQEVNFQEYVTFL 77
Cdd:cd05027  3 LEKAMVALIDVFHQYSGREGDKHKLKKSELKELINNELShfLEEIKEQEVVDKVMETLDSDGDGECDFQEFMAFV 77

S-100A11: S-100A11 domain found in proteins similar to S100A11. S100A11 is a member of the S-100 domain family within EF-hand Ca2+-binding proteins superfamily. Note that the S-100 hierarchy, to which this S-100A11 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 . S100 proteins have also been associated with a variety of pathological events, including neoplastic transformation and neurodegenerative diseases such as Alzheimer's, usually via over expression of the protein. S100A11 is expressed in smooth muscle and other tissues and involves in calcium-dependent membrane aggregation, which is important for cell vesiculation . As is the case for many other S100 proteins, S100A11 is homodimer, which is able to form a heterodimer with S100B through subunit exchange. Ca2+ binding to S100A11 results in a conformational change in the protein, exposing a hydrophobic surface that interacts with target proteins. In addition to binding to annexin A1 and A6 S100A11 also interacts with actin and transglutaminase.

                       10        20        30        40        50        60        70        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7657532   6 DQAIGLLVAIFHKYSGREGDKHTLSKKELKELIQKELTIGSKLQD--AEIARLMEDLDRNKDQEVNFQEYVTFLGALALI 83
Cdd:cd05023  5 ERCIESLIAVFQKYAGKDGDSYQLSKTEFLSFMNTELASFTKNQKdpGVLDRMMKKLDLNSDGQLDFQEFLNLIGGLAVA 84

               ....*
gi 7657532  84 YNEAL 88
Cdd:cd05023 85 CHESF 89

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 7657532   5 LDQAIGLLVAIFHKYSGregDKHTLSKKELKELIQKELTIGSKLQDAEIA--RLMEDLDRNKDQEVNFQEYVTFLGALAL 82
Cdd:cd05024  3 LEHSMEKMMLTFHKFAG---EKNYLNRDDLQKLMEKEFSEFLKNQNDPMAvdKIMKDLDDCRDGKVGFQSFFSLIAGLLI 79

               ....
gi 7657532  83 IYNE 86
Cdd:cd05024 80 ACND 83

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 7657532  28 TLSKKELKELIQKeltIGSKLQDAEIARLMEDLDRNKDQEVNFQEYVTFL 77
Cdd:cd00051 16 TISADELKAALKS---LGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62

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
                ....*....|....*....|....*..
gi 7657532   48 LQDAEIARLMEDLDRNKDQEVNFQEYV 74
Cdd:cd16226 153 MRDIVVQETLEDIDKNKDGFISLEEYI 179