CUL5
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CUL5
Cullin-5 is a protein that in humans is encoded by the ''CUL5'' gene. Discovery The mammalian gene product was originally discovered by expression cloning, due to the protein's ability to mobilize intracellular calcium in response to the peptide hormone arginine vasopressin. It was first titled VACM-1, for vasopressin-activated, calcium-mobilizing receptor. Since then, VACM-1 has been shown to be homologous to the Cullin family of proteins, and was subsequently dubbed cul5. Tissue distribution Studies have shown that the cul5 protein is expressed at its highest levels in heart and skeletal tissue, and is specifically expressed in vascular endothelium and renal collecting tubules. Function Cul5 inhibits cellular proliferation, potentially through its involvement in the SOCS/ BC-box/ eloBC/ cul5/ RING E3 ligase complex, which functions as part of the ubiquitin system for protein degradation. One study have shown that Cul5 plays a role in Reelin signaling cascade, participating in ...
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Cullin
Cullins are a family of hydrophobic scaffold proteins which provide support for ubiquitin ligases (E3). All eukaryotes appear to have cullins. They combine with RING proteins to form ''Cullin-RING ubiquitin ligases'' (CRLs) that are highly diverse and play a role in myriad cellular processes, most notably protein degradation by ubiquitination. The human genome contains eight cullin genes * CUL1, part of SCF complex * CUL2, part of ECS complex (Elongin C - CUL2 - SOCS-box) * CUL3, part of CUL3-BTB complex * CUL4A * CUL4B * CUL5 * CUL7 * CUL9, also known as PARC There is also a more distant member called ANAPC2 (or APC2), part of the Anaphase-promoting complex. CUL1, 2, 3, 4A, 4B, 5 and 7 each form part of a multi-subunit ubiquitin complex. Cullin-RING ubiquitin ligases Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regu ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ...
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Expression Cloning
Expression cloning is a technique in DNA cloning that uses expression vectors to generate a library of clones, with each clone expressing one protein. This ''expression library'' is then screened for the property of interest and clones of interest are recovered for further analysis. An example would be using an expression library to isolate genes that could confer antibiotic resistance. Expression vectors Expression vectors are a specialized type of cloning vector in which the transcriptional and translational signals needed for the regulation of the gene of interest are included in the cloning vector. The transcriptional and translational signals may be synthetically created to make the expression of the gene of interest easier to regulate. Purpose Usually the ultimate aim of expression cloning is to produce large quantities of specific proteins. To this end, a bacterial expression clone may include a ribosome binding site ( Shine-Dalgarno sequence) to enhance translation of ...
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Arginine Vasopressin
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travels down the axon terminating in the posterior pituitary, and is released from vesicles into the circulation in response to extracellular fluid hypertonicity (hyperosmolality). AVP has two primary functions. First, it increases the amount of solute-free water reabsorbed back into the circulation from the filtrate in the kidney tubules of the nephrons. Second, AVP constricts arterioles, which increases peripheral vascular resistance and raises arterial blood pressure. A third function is possible. Some AVP may be released directly into the brain from the hypothalamus, and may play an important role in social behavior, sexual motivation and pair bonding, and maternal responses to stress. Vasopressin induces differentiation of stem cells int ...
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Endothelium
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue. Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries. These cells have unique functions that include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium. An impaired function can lead to serious health issues throug ...
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Collecting Tubules
The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in electrolyte and fluid balance through reabsorption and excretion, processes regulated by the hormones aldosterone and vasopressin (antidiuretic hormone). There are several components of the collecting duct system, including the connecting tubules, cortical collecting ducts, and medullary collecting ducts. Structure Segments The segments of the system are as follows: Connecting tubule With respect to the renal corpuscle, the connecting tubule (CNT, or junctional tubule, or arcuate renal tubule) is the most proximal part of the collecting duct system. It is adjacent to the distal convoluted tubule, the most distal segment of the renal tubule. Connecting tubules from several adjacent nephrons merge to form cortical collecting tubules, and thes ...
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SOCS
SOCS (suppressor of cytokine signaling proteins) refers to a family of genes involved in inhibiting the JAK-STAT signaling pathway. Genes * CISH * SOCS1 * SOCS2 * SOCS3 * SOCS4 * SOCS5 * SOCS6 * SOCS7 Suppressor of cytokine signaling 7 is a protein that in humans is encoded by the ''SOCS7'' gene. Model organisms Model organisms have been used in the study of SOCS7 function. A conditional knockout mouse line, called ''Socs7tm1a(EUCOMM)Wtsi'' wa ... Structure All SOCS have certain structures in common. This includes a varying N-terminal domain involved in protein-protein interactions, a central SH2 domain, which can bind to molecules that have been phosphorylated by tyrosine kinases, and a SOCS box located at the C-terminal that enables recruitment of E3 ligases and ubiquitin signaling molecules. Discovery The first protein to be classified as a suppressor of cytokine signaling, CIS (cytokine-inducible SH2), was discovered in 1995, when it was found to have a unique ability ...
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Ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A. The addition of ubiquitin to a substrate protein is called ubiquitylation (or, alternatively, ubiquitination or ubiquitinylation). Ubiquitylation affects proteins in many ways: it can mark them for degradation via the proteasome, alter their cellular location, affect their activity, and promote or prevent protein interactions. Ubiquitylation involves three main steps: activation, conjugation, and ligation, performed by ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s), respectively. The result of this sequential cascade is to bind ubiquitin to lysine residues on the protein substrate via an isopeptide bond, ...
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Reelin
Reelin, encoded by the ''RELN'' gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates synaptic plasticity by enhancing the induction and maintenance of long-term potentiation. It also stimulates dendrite and dendritic spine development and regulates the continuing migration of neuroblasts generated in adult neurogenesis sites like the subventricular and subgranular zones. It is found not only in the brain but also in the liver, thyroid gland, adrenal gland, Fallopian tube, breast and in comparatively lower levels across a range of anatomical regions. Reelin has been suggested to be implicated in pathogenesis of several brain diseases. The expression of the protein has been found to be significantly lower in schizophrenia and psycho ...
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DAB1
The Disabled-1 (Dab1) gene encodes a key regulator of Reelin signaling. Reelin is a large glycoprotein secreted by neurons of the developing brain, particularly Cajal-Retzius cells. DAB1 functions downstream of Reln in a signaling pathway that controls cell positioning in the developing brain and during adult neurogenesis. It docks to the intracellular part of the Reelin very low density lipoprotein receptor (VLDLR) and apoE receptor type 2 (ApoER2) and becomes tyrosine-phosphorylated following binding of Reelin to cortical neurons. In mice, mutations of Dab1 and Reelin generate identical phenotypes. In humans, Reelin mutations are associated with brain malformations and mental retardation. In mice, Dab1 mutation results in the ''scrambler'' mouse phenotype. With a genomic length of 1.1 Mbp for a coding region of 5.5 kb, DAB1 provides a rare example of genomic complexity, which will impede the identification of human mutations. Gene function Cortical neurons form in specialize ...
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Genes Dev
''Genes & Development'' is a peer-reviewed scientific journal covering molecular biology, molecular genetics, cell biology, and development. It was established in 1987 and is published twice monthly by Cold Spring Harbor Laboratory Press in association with The Genetics Society. According to the ''Journal Citation Reports'', the journal has a 2012 impact factor of 12.44, ranking it 14th out of 181 journals in the category "Cell Biology", third out of 40 journals in the category "Developmental Biology", and 7th out of 158 journals in the category "Genetics & Heredity". Over 1999–2004, the journal was ranked fifth in the "Molecular Biology and Genetics" category according to ''ScienceWatch'', with an average of 47 citations per paper. All issues are available online via the journal website as PDFs, with a text version additionally available from August 1997. Content over 6 months old is freely available. Since 1989, the editor-in-chief has been Terri Grodzicker (Cold Spring Harbor ...
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