Search results

Members of the Rho (or ARH) protein family and other Ras-related small GTP-binding proteins are involved in various cellular procedures, such as cell cytoskeletal organization, secretion, proliferation, and signaling. The GTPBPs are active only in the GTP-bound state. At least 3 types of proteins firmly regulate cycling between the GTP-bound and GDP-bound states: GDP-dissociation inhibitors (GDIs), GTPase-activating proteins (GAPs) and guanine nucleotide-releasing factors (GRFs). ARHGDIB and the other GDIs lower the level of GDP dissociation from Ras-like GTPases.

Zinc-alpha-2-glycoprotein (ZAG) is found in body fluids such as serum, sweat, and seminal and breast cyst fluids. It is identical in amino acid sequence to tumor-derived lipid mobilizing factor (LMF), a protein associated with the dramatic loss of adipose body stores in cancer cachexia, and has been shown to stimulate lipolysis by adipocytes in vivo and in vitro. A role for ZAG has been proposed in the regulation of body weight, and age-dependent changes in genetically influenced obesity, and also it regulates melanin production by normal and malignant melanocytes. It has also recently been classified as a novel adipokine in that it is produced by both white and brown fat adipocytes and may act in a local autocrine fashion in the reduction of adiposity in cachexia. Controlling ZAG/LMF's activity could be life-saving in the management of certain cancers and other cachexiainducing conditions, and its possible normal role in body fat store homeostasis is deserving of understanding in its own right. ZAG exhibits a class I major histocompatibility complex (MHC) fold but is a soluble protein rather than being anchored to plasma membranes and does not associate with alpha-2-microglobulin in humans. Like antigen-presenting MHC class I proteins, ZAG has an open apical groove, and X-ray crystallography of human derived ZAG revealed an unidentifiable electron density in a similar position to that occupied by antigenic peptides in classical MHC proteins and glycolipids in isoforms of CD1. This presumptive ligand is not a peptide, and the groove is too small to hold a glycolipid such as is presented by CD1 isoforms. By analogy with all other MHC class I-related proteins that have an open apical groove [some do not ], occupancy by a ligand is probably crucial to ZAG's biological function. Despite all of the structural and biochemical evidence that ZAG binds a ligand, none has so far been found by extraction from protein isolated from biological fluids. This difficulty could be because the ligand is labile, heterogeneous, or readily lost during purification procedures. Knowing more about how ZAG interacts with the compounds it has been found to bind, both natural and artificial, will inform searches for the elusive ligand(s) and its/their role in ZAG's signaling function.

CTK-19 is a member of the keratin family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. The type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. Unlike its related family members, this smallest known acidic cytokeratin is not paired with a basic cytokeratin in epithelial cells. It is specifically expressed in the periderm, the transiently superficial layer that envelopes the developing epidermis. The type I cytokeratins are clustered in a region of chromosome 17q12-q21.

SSR4 is a member of the TRAP-delta family. SSR4 is the delta subunit of the translocon-associated protein complex that participates in translocating proteins through the endoplasmic reticulum membrane. SSR4 positioned in the Xq28 region and organized in a compact head-to-head manner with the isocitrate dehydrogenase 3 (NAD+) gamma gene. Both genes are motivated by a CpG-embedded bidirectional promoter.

FABP1 (Fatty acid binding protein1) encodes the fatty acid binding protein found in liver. FABP1 is composed of ten antiparallel β strands that form a barrel with a bigger binding pocket than the other FABPs allowing it to accommodate two fatty acids. This protein binds free fatty acids and their coenzyme A derivatives, bilirubin, and some other small molecules in the cytoplasm; it may be involved in intracellular lipid transport and metabolism.

HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome which produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. TARDBP is a transcriptional repressor which binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, TARDBP regulates alternate splicing of the CFTR gene. A similar pseudogene is present on chromosome 20.

Ephrin type-B receptor 4 isoform b (Ephb4) belongs to the Eph receptor tyrosine kinase family which functions in neuronal guidance and mediate venal/arterial separation. EPHB4-mediated forward signaling regulates cellular repulsion and segregation form EFNB2-expressing cells. Furthermore, Ephb4 has a role in postnatal blood vessel remodeling, morphogenesis and permeability and is therefore essential in the context of tumor angiogenesis.

Retinol Binding Protein-4 or RBP4, is the retinol currier protein in the plasma. RBP4 takes part on the conversion of retinol to the stable and soluble retinol complex in the plasma. RBP4 carries retinol from the liver tissue where its store to peripheral tissues. RBP-retinol complex has interactions with transthyretin in the plasma, thus prevents its loss by filtration in the kidney.

Lipophilin is a transmembrane proteolipid protein that is the predominant myelin protein present in the central nervous system. PLP functions in myelination. plays a role in the compaction, stabilization, and maintenance of myelin sheaths, as well as in oligodendrocyte development and axonal survival. Mutations associated with PLP gene cause X-linked Pelizaeus-Merzbacher disease and spastic paraplegia type 2. Two transcript variants encoding distinct isoforms have been identified for PLP gene.
PLP is the major myelin protein from the central nervous system and plays an important role in the formation or maintenance of the multilamellar structure of myelin.

Adiponectin is a recently discovered 244 amino acid protein, the product of the apM1 gene, which is physiologically active and specifically and highly expressed in adipose cells (Adipokine). The protein belongs to the soluble defense collagen super family; it has a collagen-like domain structurally homologous with collagen VIII and X and complement factor C1q-like globular domain. APM-1 forms homotrimers, which are the building blocks for higher order complexes found circulating in serum.

DnaJB2 is a member of the DnaJ family. The DnaJ family is one of the largest of all the chaperone families which has evolved with diverse cellular localization and functions. DnaJB2 are important mediators of proteolysis which are involved in the regulation of protein degradation, exocytosis and endocytosis. The DnaJ proteins play a significant role in the HSP70 chaperone machine by interacting with HSP70 to stimulate ATP hydrolysis. DnaJB2 is expressed almost solely in the brain, with the highest levels in the frontal cortex and hippocampus.

Sonic Hedgehog is part of a small group of secreted proteins which are vital for development in both vertebrates and invertebrates. 3 mammalian hedgehog genes (sonic, desert, Indian) share about 60% homology. The Human Sonic Hedgehog is 99% homologous to the mouse gene. Sonic HedgeHog is a protein that is vital in guding the early embryo. It has been associated as the major inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Sonic HedgeHog binds to the patched receptor, which functions in association with smoothened, to activate the transcription of target genes. In the absence of sonic HedgeHog, patched receptor represses the constitutive signaling activity of smoothened. Sonic HedgeHog also regulates another factor, the gli oncogene. Sonic HedgeHog intercellular signal is essential for a various patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Sonic HedgeHog exhibits both floor plate- and motor neuron-inducing activity. Mutations in a long-range Sonic HedgeHog enhancer located in an intron of the limb region 1 gene result in preaxial polydactyly.

SLPI is a secreted inhibitor which guards epithelial tissues from serine proteases. SLPI is localized in various secretions including seminal plasma, cervical mucus, and bronchial secretions, and has affinity for trypsin, leukocyte elastase, and cathepsin G. SLPI inhibitory effect contributes to the immune response by protecting epithelial surfaces from attack by endogenous proteolytic enzymes. SLPI protein has broad-spectrum anti-biotic activity. SLPI is an acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. SLPI prevents elastase-mediated damage to oral and mucosal tissues.

CCNB2 is a member of the cyclin family. CCNB2 is vital for regulation of the cell cycle at the G2/M (mitosis) transition. CCNB2 cooperates with the CDK1 protein kinase to create a serine/threonine kinase holoenzyme complex recognized as maturation promoting factor (MPF).

L-Selectin belongs to a family of divalent cation-dependent carbohydrate-binding glycoproteins or adhesion molecules. The L-Selectin molecule is composed of various domains: one homologous to lectins, one to epidermal growth factor, and two to the consensus repeat units found in C3/C4 binding proteins.
L-selectin is expressed constitutively on lymphocytes, monocytes and granulocytes and interacts specifically with carbohydrate groups on activated endothelial cells. L-Selectin may be shed by proteolytic cleavage and circulating levels in biological fluids may be used as an indicator of various pathological conditions. L-Selectin is cleaved by ADAM17.
L-selectin works as a "homing receptor" for leukocytes to enter secondary lymphoid tissues via the high endothelial venules. Ligands present on endothelial cells will attach to leukocytes expressing L-selectin, which causes the leukocytes to become localized at that juncture. The receptor is also located on the cell surfaces of "naive" T cells, which have not yet encountered their particular antigen. This surface expression is lost following the cells activation.

Delta-Like4, also known as DLL4 is implicated in the Notch signaling pathway as Notch ligand. Consequently DLL4 negatively regulates endothelial cell proliferation, migration as well as angiogenic sprouting. DLL4 is vital for retinal progenitor proliferation and also required for suppressing rod fates in late retinal progenitors and for proper generation of other retinal cell types. Furthermore, at some stage in the spinal cord neurogenesis, DLL4 inhibits V2a interneuron fate.

Ataxin 3 is otherwise known as Machado-Joseph disease protein 1. Machado–Joseph disease is a hereditary autosomal dominant neurodegenerative disorder. ATXN3 contains trinucleotide CAG repeats in the coding region, and the expansion of these repeats from the normal 13-36 to 68-79 causes the Machado-Joseph disease. ATXN3 is a poly-ubiquitin-binding protein whose cellular turnover is regulated by its catalytic activity.
In addition, ATXN3 is a proteasome-associated factor which mediates the degradation of ubiquitinated proteins. ATXN3 folds reversibly using a single intermediate; partial destabilization of ATXN3 by chemical denaturation causes the formation of fibrillar aggregates by the non-pathological variant.
Ataxin-3 interacts with the major histone acetyltransferases cAMP-response-element binding protein (CREB)-binding protein, p300, and p300/CREB-binding protein-associated factor and hinders transcription by these coactivators.

Heat Shock Factor Binding Protein 1-Like 1 (HSBP1L1) is a part of a family of eukaryotic proteins known as nucleotide exchange factors for HSP 70. HSBP1L1 is a protein coding gene whose expression is regulated mainly at the transcription level.

Signal-Regulatory Protein Gamma (SIRPG) belongs to the signal-regulatory protein (SIRP) family whose members are receptor-type transmembrane glycoproteins which negatively regulate the receptor tyrosine kinase-coupled signaling processes. SIRPG is also a part of the immunoglobulin superfamily.

Ephrin-B3 (EFNB3) which belongs to the ephrin gene family is essential in brain development as well as in its maintenance. EFNB3 binds to, and induces the collapse of, commissural axons/growth cones in vitro. EFNB3 loosely binds Eph receptors located on bordering cells, leading to contact-dependent bidirectional signaling into neighboring cells. The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and are implicated in mediating developmental events, mostly in the nervous system.