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Abstract: Protein families characterized by a ligand binding domain related to that of oxysterol binding protein (OSBP) have been identified in eukaryotic species from yeast to humans. These proteins, designated OSBP‐related (ORP) or OSBP‐like (OSBPL) proteins, have been implicated in various cellular functions. However, the detailed mechanisms of their action have remained elusive. Data from our and other laboratories suggest that binding of sterol ligands may be a unifying theme. Work with Saccharomyces cerevisiae ORPs suggests a function of these proteins in the nonvesicular intracellular transport of sterols, in secretory vesicle transport from the Golgi complex, and in the establishment of cell polarity. Mammals have more ORP genes, and differential splicing substantially increases the complexity of the encoded protein family. Functional studies on mammalian ORPs point in different directions: integration of sterol and sphingomyelin metabolism, sterol transport, regulation of neutral lipid metabolism, control of the microtubule‐dependent motility of endosomes/lysosomes, and regulation of signaling cascades. We envision that during evolution, the functions of ORPs have diverged from an ancestral one in sterol transport, to meet the increasing demand of the regulatory potential in multicellular organisms. Our working hypothesis is that mammalian ORPs mainly act as sterol sensors that relay information to a spectrum of different cellular processes. [Copyright &y& Elsevier]

The article presents an encyclopedia entry for cytokine receptors, which are binding proteins for mediators of the immune system. It describes the characteristics of cytokines. The regulation of cytokine receptors are on different levels. It discusses the functions of cytokine receptors. It provides information on the preclinical relevance of cytokine receptors.

A definition of the term "Membrane transport proteins" is presented. It refers to an integral transmembrane proteins and transport substances with a high degree of specificity. Due to differences in their mechanism of action, the rate of transport differs considerably between different types of transport proteins. Channel proteins transport water or specific ions down their concentration gradients or electric potential gradients.

An encyclopedia entry for the term "insulin-like growth factors" (IGF) is presented. IGF is a family of insulin growth factors related proteins that are structurally and functionally related to insulin. Protein members of IGF include binding proteins and cell surface receptors. IGF is important in development during embryonic stage and in post-natal growth and development.

The article presents an encyclopedia entry on the definition of the term "GTPase." The term, also known as guanosine triphosphatase (GTP)-binding proteins, G-proteins or small GTP-binding proteins are members of the Ras superfamily. They are enzymes that catalyzes the hydrolysis of GTP to guanosine 5'-diphosphate and inorganic phosphate.

The article provides information on hapten. It was introduced by Karl Landsteiner in the 1920s to define low molecular weight chemical reagents which will not induce immune responses. Carriers that are foreign to the immunized individuals result in antibodies and T cells directed against the attached hapten as well as the carrier protein. For many hapten-specific T cells the carrier peptides mainly serve to anchor and position the hapten moiety on the MHC surface.

A definition of the term "hapten" is presented. It refers to a non-immunogenic compound of low relative molecular mass which becomes immunogenic after conjugation with a carrier protein or cell and so induces an immune response. It mentions that the binding of a hapten to a protein allows presentation of the hapten in the peptic-binding groove of MHC molecules.

A definition of the term "heterotrimeric GTP-binding proteins" is presented. Heterotrimeric G-proteins are part of a widely used transmembrane signaling system consisting of G-protein coupled receptors or binding proteins, heterotrimeric G-proteins and a variety of effectors (enzymes or ion channels).

A definition of the term "co-operativity factor" is presented. It refers to a receptor protein mediated through the binding of the allosteric ligand and to the allosteric binding protein. A change in the affinity of the receptor for other ligands or the efficacy of a ligand for the receptor, is quantified by the co-operativity factor.

A definition of "transferrin receptor" is presented. It refers to cell membrane receptors for transferrin. They have a role in iron uptake by the cell and are highly expressed in proliferating cells.

A definition of the term "lectins" is presented. It refers to a family of carbohydrate-binding proteins found in animals and plants. The different type of lectins recognize specific carbohydrate ligands.

The article explains the hapten theory. It is noted that the basic paradigm for the induction of skin sensitization postulates chemical reactivity of a low-molecular-weight chemical, which leads to the formation of hapten-carrier conjugates composed of self-proteins covalently linked with the chemical. The hapten concept can also be applied to some drug allergies, which are induced after oral administration of the drug like immune-mediated anemias and leukocytopenias.

The article presents an encyclopedia entry for corticosteroid-binding globulin (CBG), sometimes referred to as transcortin, which binds to corticosteroids with high avidity. CBG-corticosteroid complex is too large to enter cells since the glucocorticoid receptor is located within the cytosol. Stressful events decrease the circulating levels of CBG, thus increasing the fraction of biologically active glucocorticoids.

The article presents an encyclopedia entry for "cytokine receptor," which are binding proteins for cytokines. Cytokine receptors are capable of binding their ligand with a high affinity. A term is used for the ligand binding protein in the signaling of cytokine receptors. It also has the ability to bind cytokines.

An encyclopedia entry for "insulin-like growth factor" is presented. Insulin-like growth factor IGF1 and IGF2 are widely expressed peptides with sequence homology to insulin. Both factors bind to specific receptors. The IGF1 receptor is a receptor tyrosine kinase with the same structure and molecular function to the insulin receptor.

A definition of the term "importins," which refers to transport proteins at the nuclear pore complex, is presented.

A definition of the term "immunophilin," which refers to the intracellular binding proteins of several immunosuppressive drugs, is presented.

A reference entry for the acronym "CREB" is presented. It stands for cyclic-AMP response element binding protein. Phosphorylation enables to this transcription factor to binds with gene promoters that contain a specific binding site. It modulates transcription activity. It is linked with antidepressant drugs.

A definition of the term "COPI vesicle" is presented. It refers to transport intermediates which affect anterograde transport from the intermediate compartment to the Golgi, transport within the Golgi apparatus apparatus and retrograde transport back from the Golgi to the ER by the recruitment of soluble proteins from the cytoplasm.

A definition of the term "Bartter's syndrome" is presented. It refers to an electrolyte disorder that has been recognized to be caused by mutations in at least three transport proteins responsible for sodium chloride absorption in the loop of Henle. It can also be caused by mutations in the potassium channel that is present in the apical membrane of the ascending limb.

A definition of the term "ATP-binding cassette transporter superfamily" is presented. The ATP-binding cassette (ABC) transporters, or proteins, which are characterized by having so-called ATP-binding cassette domain, function as pumps, channels and channel regulators. ABC proteins have multiple membrane-spanning segments and nucleotide-binding folds in the cytoplasmic side, which contain highly conserved Walker motifs and an ABC signature sequence.

An encyclopedia entry for actin binding proteins, as used in molecular pharmacology, is presented.

A definition of the term "USF Family" is presented. It refers to a group of bHLH proteins which bind DNA as homodimers.

A definition of the term "translin" is presented. Also known as testis brain-RNA binding protein, translin (TSN) refers to an RNA- and single-stranded DNA binding protein. The RNA-binding interactions of TSN have been linked with the regulation of translation during spermiogenesis and transport of messenger RNA in the nervous system.

A definition of the term "TOR" is presented. It refers to a part of the general mitotic signaling pathway that involve a tyrosine kinase, phosphatidylinositol 3-kinase, Akt/PKB kinase, p70S6 kinase and 4E-BPI. The phosphatidylinositol kinase homologue TOR is the cellular target of FK506 binding protein.

A definition of "sterol regulatory element binding transcription factor (Srebp)/Add family group" is presented. Srebp/Add family is a group of bhlh proteins. It is composed of Srebpl, Srebp2, Add1, which are involved in cholesterol homeostasis, sterol synthesis and adipocyte determination. Srebp produces N-terminal fragments that enter the nucleus and activate transcription.

A definition of "sterol regulatory element binding protein-2" (Srebp2) is presented. It is a bHLH protein member of the Srebp/Add family of 1141 amino acids and 123 kD. Srebp2 is a transcriptional activator that binds to the sterol regulatory element 1 (sre-1). sre-1 is found in the flanking regions of the Ldrl and Hmg- CoA synthase genes.

A definition of "sterol regulatory element 1" (sre-1) is presented. sre-1 refers to the sequence found in the flanking region of different genes responsive to sterols. Sterol regulatory element binding transcription factor 1 has dual sequence specificity (Srebp1). Srebp1 binds with sre-1 and the E-box motif.

An encyclopedia entry for silencing-mediator-repressor-transcription (SMRT) and nuclear-hormone-co-repressor (N-CoR) is presented. SMART and N-CoR are related co-repressors that combine DNA binding proteins with histone deacetylases.

A definition of the article "rapamycin," as used in cancer terminology, is presented. It refers to a bacterial macrolide with antibiotic and immunosuppressive activity and structural similarity to FK506. It inhibits target of rapamycin in a complex with FK506 binding protein. Treatment of cells using rapamycin leads to dephosphorylation and inactivation of p70S6 kinase an also to dephosphorylation of 4E-BP1.

A definition of the term "p14ARF" is presented. It refers to a protein that binds to, and promotes, degradation of MDM2, thereby releasing functional p53.

A definition of the term "multidrug resistance-associated protein" is presented. It refers to a member of the ATP-binding cassette superfamily of transporter proteins. It is responsible for the efflux of anionic conjugates of lipophilic compounds from the cell. Many of the substrates are products of phase 2 drug metabolism.

A definition of the term "multidrug-resistance protein (MRP)" is presented. It refers to a member of the ATP-binding cassette superfamily of transporter proteins. It is responsible for the efflux of hydrophobic xenobiotics from cells. MRP is located in the cell membrane of some normal and tumor cells.

An encyclopedia entry for the term "MNT," is presented. MNT stands for Myc antagonist. It is also known as MAX binding protein. It is capable of encoding a nuclear basic helix-loop-helix protein of 582 aa and 62 kD. The protein binds DNA as a heterodimer with MAX at the E-box CACGTG and represses transcription by antagonizing MYC.

A definition of the term "insulin-like binding proteins" is presented. These are large molecular proteins seen in local tissue environments and in circulation. Insulin-like binding proteins tie up insulin-like growth factors (IGF). These proteins tie up IGF to regulate their half-life and functions.

A definition of the term "IGFBP" is presented. The term stands for insulin-like growth factors-binding protein.

A definition of the term "heterotrimeric GTP-binding proteins," is presented, which refers to the GTP-binding proteins with three subunits; the α subunit has the ability to bind GTP, while the β and γ subunits do not bind to GTP. Both the α and βγ subunits are able to particularly interact and activate a variety of effector molecules.

This entry provides the definition of the term "GSP." The term is synonymous with guanine nucleotide binding protein alpha stimulating activity polypeptide 1. The term refers to a guanine nucleotide binding adenylate cyclase-stimulating protein.

A definition of the term "EWS" is presented. It refers to a Ewing sarcoma protein. It is described as a nuclear RNA-binding protein of unknown function which interacts with calmodulin. This Ewing sarcoma gene is identified as a gene on chromosome 22. It is disrupted consistently by chromosomal translocation in Ewing sarcoma family tumors.

A definition of the term "DNA ducts," which refers to covalent binding products formed between a chemical and DNA, is presented.

A definition of the term "EP300" is presented. EP300, or E1A binding protein p300, is a nuclear protein, a probable transcriptional adaptor required for the activity of certain complex transcriptional regulatory elements. It functions by connecting the basal transcriptional machinery to various DNA binding factors and connects this to its tissue specific expression.

A definition of the term "domain of protein" is presented, which refers to a region with a specific amino acid sequence that serves as an interface for binding to other proteins or DNA.

An encyclopedia entry for the acronym CREB is presented. This stands for cyclic AMP response element binding protein. It is basic leucine zipper transcription factor which binds the cyclic AMP response element (CRE) consensus motif TGACGTCA. It is originally isolated as the protein which bound the CRE in the somatostatin gene.

A definition of the term "CBP/p300" is presented. CBP/p300 is a cAMP-responsive element binding protein and is a co-activator activator for several transcription factors by bridging them to the basal transcriptional machinery and through their intrinic histone acetyltranslerase activity.

A definition of the term "AP-2" is presented, which refers to the activating enhancer-binding protein 2, also known as AP2TF and TFAP2, which is a transcription factor that maps to 6p22.3-ter, that is a gene responsive to retinoic acid. It is a nuclear protein of 52 kD, and as a dimer sticks to the DNA consensus sequence 5′-CCCCAGGC-3′.