query: what is the primary function of the endoplasmic reticulum

pos: Endoplasmic reticulum bound to their membranes and drifting within the confines of their lumens. This fundamental difference is indicative of their functions: The endoplasmic reticulum synthesizes molecules, while the sarcoplasmic reticulum stores calcium ions and pumps them out into the sarcoplasm when the muscle fiber is stimulated. After their release from the sarcoplasmic reticulum, calcium ions interact with contractile proteins that utilize ATP to shorten the muscle fiber. The sarcoplasmic reticulum plays a major role in excitation-contraction coupling. The endoplasmic reticulum serves many general functions, including the folding of protein molecules in sacs called cisternae and the transport of synthesized proteins in

neg: Endoplasmic reticulum membrane protein complex mEMC assumes (an) important function(s) in cancerous cells to establish a malignant tumour. Mutations in the EMC1 gene have been associated with retinal dystrophy and a severe systemic disease phenotype involving developmental delay, cerebellar atrophy, scoliosis and hypotonia. Similarly, a homozygous missense mutation (c.430G>A, p.Ala144Thr) within the EMC1 gene has been correlated with the development of retinal dystrophy. Even though a set of disease-causing mutations in EMC1 has been mapped, their effect on EMC1 function and structure remain to be studied. Endoplasmic reticulum membrane protein complex The endoplasmic reticulum membrane protein complex (EMC) is a putative endoplasmic reticulum-resident membrane protein

neg: Endoplasmic reticulum general structure of the endoplasmic reticulum is a network of membranes called cisternae. These sac-like structures are held together by the cytoskeleton. The phospholipid membrane encloses the cisternal space (or lumen), which is continuous with the perinuclear space but separate from the cytosol. The functions of the endoplasmic reticulum can be summarized as the synthesis and export of proteins and membrane lipids, but varies between ER and cell type and cell function. The quantity of both rough and smooth endoplasmic reticulum in a cell can slowly interchange from one type to the other, depending on the changing metabolic activities of

neg: Endoplasmic reticulum membrane protein complex Endoplasmic reticulum membrane protein complex The endoplasmic reticulum membrane protein complex (EMC) is a putative endoplasmic reticulum-resident membrane protein (co-)chaperone. The EMC is evolutionarily conserved in eukaryotes (animals, plants, and fungi), and its initial appearance might reach back to the last eukaryotic common ancestor (LECA). Many aspects of mEMC biology and molecular function remain to be studied. , the structure of the EMC has not yet been resolved. The EMC consists of up to 10 subunits (EMC1 - EMC4, MMGT1, EMC6 - EMC10), of which only two (EMC8/9) are homologous proteins. Seven out of ten (EMC1, EMC3, EMC4, MMMGT1, EMC6,

neg: STIM1 STIM1 Stromal interaction molecule 1 is a protein that in humans is encoded by the "STIM1" gene. STIM1 has a single transmembrane domain, and is localized to the endoplasmic reticulum, and to a lesser extent to the plasma membrane. Even though the protein has been identified earlier, its function was unknown until recently. In 2005, it was discovered that STIM1 functions as a calcium sensor in the endoplasmic reticulum. Upon activation of the IP3 receptor, the calcium concentration in the endoplasmic reticulum decreases, which is sensed by STIM1, via its EF hand domain. STIM1 activates the "store-operated" ORAI1 calcium ion

neg: Endoplasmic reticulum processes that may even contribute to Alzheimer's disease. In the colon, XBP1 anomalies have been linked to the inflammatory bowel diseases including Crohn's disease. The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum. The UPR is activated in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum. The UPR functions to restore normal function of the cell by halting protein translation, degrading misfolded proteins, and activating the signaling pathways that lead to increasing the production of molecular chaperones involved in protein folding. Sustained overactivation of the UPR

neg: Wolfram syndrome reticulum folds and modifies newly formed proteins so they have the correct 3-dimensional shape to function properly. The endoplasmic reticulum also helps transport proteins, fats, and other materials to specific sites within the cell or to the cell surface. The function of wolframin is unknown. Based on its location in the endoplasmic reticulum, however, it may play a role in protein folding or cellular transport. In the pancreas, wolframin may help fold a protein precursor of insulin (called proinsulin) into the mature hormone that controls blood glucose levels. Research findings also suggest that wolframin may help maintain the correct cellular

neg: Endoplasmic reticulum Endoplasmic reticulum The endoplasmic reticulum (ER) is a type of organelle found in eukaryotic cells that forms an interconnected network of flattened, membrane-enclosed sacs or tube-like structures known as cisternae. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum occurs in most types of eukaryotic cells, but is absent from red blood cells and spermatozoa. There are two types of endoplasmic reticulum: rough (granular) and smooth (agranular). The outer (cytosolic) face of the rough endoplasmic reticulum is studded with ribosomes that are the sites of protein synthesis. The rough endoplasmic reticulum is especially prominent

neg: Peter K. Hepler specify the biophysical mechanisms involved in organization. After Richard Weisenberg discovered that microtubule polymerization was sensitive to calcium concentration, Hepler realized that he had already seen a close association between elements of the endoplasmic reticulum and microtubules in the mitotic apparatus and in the phragmoplast and suggested that these membranes may function in controlling the concentration of free calcium in the mitotic apparatus. Along with Susan Wick and Steve Wolniak, Hepler showed that the endoplasmic reticulum contained stores of calcium and suggested that the endoplasmic reticulum may locally control the calcium concentration and thus the polymerization/depolymerization of microtubules. Subsequently, Hepler,

neg: Endoplasmic reticulum Vesicles are surrounded by coating proteins called COPI and COPII. COPII targets vesicles to the Golgi apparatus and COPI marks them to be brought back to the rough endoplasmic reticulum. The rough endoplasmic reticulum works in concert with the Golgi complex to target new proteins to their proper destinations. A second method of transport out of the endoplasmic reticulum involves areas called membrane contact sites, where the membranes of the endoplasmic reticulum and other organelles are held closely together, allowing the transfer of lipids and other small molecules. The rough endoplasmic reticulum is key in multiple functions: In most cells

neg: TMEM33 ran on TMEM33 showed that the protein bound to reticulon 4C, 1A, 2B, 3C, and Arl6IP1 in vitro. TMEM33 was found to interact with ubiquitin C, ubiquitin specific peptidase 19 (USP19), 40S ribosomal protein S14 (RPS14), replication protein A (RPA1, RPA2, RPA3), transitional endoplasmic reticulum ATPase (VCP), and RNA polymerase III initiation factor (BRF2) using affinity capture experiments with those proteins as bait. Coimmunoprecipitation ecperiment found two-pore channel (TPC), an ion channel, and TMEM33 bind. TMEM33 localizes to the endoplasmic reticulum (ER) membrane and the nuclear envelope, and therefore must function in these regions. TMEM33 exogenously suppresses reticulon 4C function,

neg: Glycosome be attached to the sarcoplasmic reticulum and its intermediate filaments. Other glycosomes have been found to be attached to myofibrils and mitochondria, rough endoplasmic reticulum, sarcolemma, polyribosomes, or the Golgi apparatus. Glycosome attachment may bestow a functional distinction between them; the glycosomes attached to the myofibrils seem to serve the myosin by providing energy substrates for generation of ATP through glycolysis. The glycosomes in the rough and smooth endoplasmic reticulum make use of its glycogen synthase and phosphorylase phosphatases. Glycosomes function in many processes in the cell. These processes include glycolysis, purine salvage, beta oxidation of fatty acids, and ether

neg: Endoplasmic reticulum has been implicated in prion diseases as well as several other neurodegenerative diseases and the inhibition of the UPR could become a treatment for those diseases. Endoplasmic reticulum The endoplasmic reticulum (ER) is a type of organelle found in eukaryotic cells that forms an interconnected network of flattened, membrane-enclosed sacs or tube-like structures known as cisternae. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum occurs in most types of eukaryotic cells, but is absent from red blood cells and spermatozoa. There are two types of endoplasmic reticulum: rough (granular) and smooth (agranular). The

neg: PDIA3 protein disulfide isomerase activity. PDIA3 is also part of the major histocompatibility complex (MHC) class I peptide loading complex, which is essential for formation of the final antigen conformation and export from the endoplasmic reticulum to the cell surface. This protein of the endoplasmic reticulum interacts with lectin chaperones such as calreticulin and CNX in order to modulate the folding of proteins that are newly synthesized. It is believed that PDIA3 plays a role in protein folding by promoting the formation of disulfide bonds, and that CNX facilitates the positioning substrates next to the catalytic cysteines. This function allows it

neg: Unfolded protein response Unfolded protein response The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum (ER) stress. It is a stress response that has been found to be conserved between all mammalian species, as well as yeast and worm organisms. This article focuses on the mammalian response. The UPR is activated in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum. In this scenario, the UPR has three aims: initially to restore normal function of the cell by halting protein translation, degrading misfolded proteins, and activating the signalling pathways that

neg: Endoplasmic reticulum of tubules that are located near the cell periphery. These tubes sometimes branch forming a network that is reticular in appearance. In some cells, there are dilated areas like the sacs of rough endoplasmic reticulum. The network of smooth endoplasmic reticulum allows for an increased surface area to be devoted to the action or storage of key enzymes and the products of these enzymes. The sarcoplasmic reticulum (SR), from the Greek σάρξ "sarx" ("flesh"), is smooth ER found in myocytes. The only structural difference between this organelle and the smooth endoplasmic reticulum is the medley of proteins they have, both

neg: Peter Walter into the endoplasmic reticulum (ER) and showed that it selectively recognizes nascent secretory proteins in the cytoplasm of eukaryotic cells and targets them to the ER. He subsequently identified a 7S RNA component of the complex which is essential for its function and named the holocomplex the signal recognition particle (SRP). Walter moved from Rockefeller to start his own laboratory at the University of California, San Francisco, where he and his group identified an ER resident transmembrane kinase/endoribonuclease, Ire1, which is one of three known sensors of the folding capacity within the endoplasmic reticulum lumen responsible for initiating a signaling

neg: Nucleolus result in the formation of the 40S (small) and 60S (large) subunits of the complete ribosome. These are exported through the nuclear pore complexes to the cytoplasm, where they remain free or become associated with the endoplasmic reticulum, forming rough endoplasmic reticulum (RER). In human endometrial cells, a network of nucleolar channels is sometimes formed. The origin and function of this network has not yet been clearly identified. In addition to its role in ribosomal biogenesis, the nucleolus is known to capture and immobilize proteins, a process known as nucleolar detention. Proteins that are detained in the nucleolus are unable

neg: Sarcoplasmic reticulum ryanodine receptors (known as stochastic attrition), or the ryanodine receptors becoming inactive after a calcium spark, while others believe that a decrease in SR calcium, triggers the receptors to close (see calcium sparks for more details). The breakdown of the sarcoplasmic reticulum, along with the resultant release of calcium, is an important contributor to rigor mortis, the stiffening of muscles after death. Sarcoplasmic reticulum The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca). Calcium ion

neg: GDP-fucose protein O-fucosyltransferase 1 decreased to very low levels, all Notch signaling is destroyed, which means that fucose on Notch is essential for Notch function. Why this is the case is not yet well understood. Almost all glycosyltransferases reside in the Golgi apparatus. However, POFUT1 as well as the related enzyme POFUT2 have recently been shown to reside in the endoplasmic reticulum. POFUT-1 is involved in the attachment of Fucose sugars to a lot of proteins, However a key pathway is the Post-transitional Modification of NOTCH signal proteins. Pre-NOTCH proteins are translated and deposited in to the endoplasmic reticulum and are then first modified

neg: Paraptosis Honokiol, a compound derived from "Magnolia officinalis", can induce paraptosis in human leukemia cells. In the NB4 cell line, paraptosis was the primary method of cell death. In K562 cells, apoptosis was the primary mechanism, with paraptosis occasionally found. Researchers stated that this suggests that leukemia cell death can be induced by multiple pathways. In one experiment a phosphine copper(I) complex caused paraptosis in colon cancer cells by inducing endoplasmic reticulum stress. Another copper complex, the A0 thioxotriazole copper (II) complex, also caused paraptosis in HT1080 fibrosarcoma cells via endoplasmic reticulum stress and cytoplasmic vacuolization. Along with cytotoxic effects such

neg: Endoplasmic-reticulum-associated protein degradation yeast. Humans have the homolog of Cdc48p known as valosin-containing protein (VCP/p97) with the same function as Cdc48p. VCP/p97 transports substrates from the endoplasmic reticulum to the cytoplasm with its ATPase activity. The ubiquitination of terminally misfolded proteins is caused by a cascade of enzymatic reactions. The first of these reactions takes place when the ubiquitin-activating enzyme E1 hydrolyses ATP and forms a high-energy thioester linkage between a cysteine residue in its active site and the C-terminus of ubiquitin. The resulting activated ubiquitin is then passed to E2, which is a ubiquitin-conjugating enzyme. Another group of enzymes, more specifically ubiquitin

neg: Lamin role in anchoring the nucleus to the endoplasmic reticulum, forming a continuous unit within the cell. This is accomplished by lamin and lamin-interacting proteins (SUN1/SUN2) connecting with proteins on the outer nuclear membrane. These proteins in turn interact with cytoskeletal elements of the endoplasmic reticulum, forming a strong complex that can withstand mechanical stress. Nuclei that lack lamins or have mutated versions have a deformed shape and do not function properly. During mitosis, lamins are phosphorylated by Mitosis-Promoting Factor (MPF), which drives the disassembly of the lamina and the nuclear envelope. This allows chromatin to condense and the DNA to

neg: Sarcoplasmic reticulum Sarcoplasmic reticulum The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca). Calcium ion levels are kept relatively constant, with the concentration of calcium ions within a cell being 100,000 times smaller than the concentration of calcium ions outside the cell. This means that small increases in calcium ions within the cell are easily detected and can bring about important cellular changes (the calcium is said to be a second messenger; see calcium in biology for

neg: Endoplasmic reticulum the cell. Transformation can include embedding of new proteins in membrane as well as structural changes. Changes in protein content may occur without noticeable structural changes. The surface of the rough endoplasmic reticulum (often abbreviated RER or Rough ER) (also called "granular endoplasmic reticulum") is studded with protein-manufacturing ribosomes giving it a "rough" appearance (hence its name). The binding site of the ribosome on the rough endoplasmic reticulum is the translocon. However, the ribosomes are not a stable part of this organelle's structure as they are constantly being bound and released from the membrane. A ribosome only binds to the

neg: Small ubiquitin-related modifier 1 of breath. Patients with heart failure have a significantly increased risk of death compared to people with normal heart function. Heart failure is a major public health concern, as its incidence is on the rise worldwide, and is a leading cause of death in developed nations SUMO 1 is a key component in cardiac function, since it helps regulate calcium homeostasis in the mitochondria of heart cells. SUMO 1 is associated with another essential cardiac protein called sarco/endoplasmic reticulum Ca2+ ATPase, or SERCA2A. SERCA is a transmembrane protein located in the sarcoplasmic reticulum of cardiac cells. Its main function is

neg: Endoplasmic reticulum those in the testes, ovaries, and sebaceous glands have an abundance of smooth endoplasmic reticulum. It also carries out the metabolism of carbohydrates, detoxification of natural metabolism products and of alcohol and drugs, attachment of receptors on cell membrane proteins, and steroid metabolism. In muscle cells, it regulates calcium ion concentration. Smooth endoplasmic reticulum is found in a variety of cell types (both animal and plant), and it serves different functions in each. The smooth endoplasmic reticulum also contains the enzyme glucose-6-phosphatase, which converts glucose-6-phosphate to glucose, a step in gluconeogenesis. It is connected to the nuclear envelope and consists

neg: Glycan mannose, and other monosaccharides. In eukaryotes, N-linked glycans are derived from a core 14-sugar unit assembled in the cytoplasm and endoplasmic reticulum. First, two "N"-acetyl glucosamine residues are attached to dolichol monophosphate, a lipid, on the external side of the endoplasmic reticulum membrane. Five mannose residues are then added to this structure. At this point, the partially finished core glycan is flipped across the endoplasmic reticulum membrane, so that it is now located within the reticular lumen. Assembly then continues within the endoplasmic reticulum, with the addition of four more mannose residues. Finally, three glucose residues are added to this

neg: Endoplasmic-reticulum-associated protein degradation mimics substrates for the E3 complex SCF. In cells that are infected with HIV, SCF interacts with Vpu and ubiquitinates CD4, which is subsequently degraded by the proteasome. Vpu itself escapes from the degradation. The big open questions related to ERAD are: Endoplasmic-reticulum-associated protein degradation Endoplasmic-reticulum-associated protein degradation (ERAD) designates a cellular pathway which targets misfolded proteins of the endoplasmic reticulum for ubiquitination and subsequent degradation by a protein-degrading complex, called the proteasome. The process of ERAD can be divided into three steps: The recognition of misfolded or mutated proteins depends on the detection of substructures within proteins such as

neg: Birdshot chorioretinopathy may be associated with HLA-A29 in the pathogenesis. In 2014, Kuiper et al. conducted a genome-wide association study in birdshot chorioretinopathy and studied the entire genome of Dutch, Spanish and English patients. This large genetic study ascertained HLA-A29:02 as the primary risk factor and identified the "endoplasmic reticulum aminopeptidase (ERAP) 2" gene strongly associated with birdshot chorioretinopathy. Genetic variants near "ERAP2" on chromosome 5 resulted in high mRNA and protein expression of this aminopeptidase in BSCR patients. ERAP2 is an aminopeptidase that, together with the closely related ERAP1, trims peptides in the endoplasmic reticulum and loads these peptides on HLA

neg: Odontoblast Odontoblast In vertebrates, an odontoblast is a cell of neural crest origin that is part of the outer surface of the dental pulp, and whose biological function is dentinogenesis, which is the formation of dentin, the substance beneath the tooth enamel on the crown and the cementum on the root. Odontoblasts are large columnar cells, whose cell bodies are arranged along the interface between dentin and pulp, from the crown to cervix to the root apex in a mature tooth. The cell is rich in endoplasmic reticulum and Golgi complex, especially during primary dentin formation, which allows it to have

neg: Endoplasmic reticulum stress in beta cells diabetes) can activate ER stress in beta cells. Causes such as defective protein processing and trafficking or inappropriate calcium regulation are likely in lipid-mediated ER stress. On the other hand, cytokines are likely to activate ER stress by decreasing the calcium pump "Serca2b" (also known as "Atp2a2"), leading to subsequent depletion in the ER calcium stores. Activation of ER stress by lipids results in a typical UPR to primarily restore ER function, whereas cytokine-activated ER stress leads to an atypical UPR that preferentially activate apoptosis in beta cells. Endoplasmic reticulum stress in beta cells Beta cells are heavily engaged in

neg: Translocon heterotrimer Sec61. Further known components of the translocon complex are the oligosaccharyl transferase complex, the TRAP complex, and the membrane protein TRAM. For further components, such as signal peptidase complex and the SRP receptor it is not clear to what extent they only associate transiently to the translocon complex. Proteins due to be translocated to the endoplasmic reticulum are recognized by the signal-recognition particle (SRP), which halts translation of the polypeptide by the ribosome while it attaches the ribosome to the SRP receptor on the endoplasmic reticulum. This recognition event is based upon a specific N-terminal signal sequence that is

neg: Calmodulin activation of MLC kinase. Another way that calmodulin affects muscle contraction is by controlling the movement of Ca across both the cell and sarcoplasmic reticulum membranes. The Ca channels, such as the ryanodine receptor of the sarcoplasmic reticulum, can be inhibited by calmodulin bound to calcium, thus affecting the overall levels of calcium in the cell. Calcium pumps take calcium out of the cytoplasm and/or store it in the endoplasmic reticulum and this control helps regulate many downstream processes. This is a very important function of calmodulin because it indirectly plays a role in every physiological process that is affected

neg: Endoplasmic reticulum in cells such as hepatocytes. The smooth endoplasmic reticulum lacks ribosomes and functions in lipid manufacture and metabolism, the production of steroid hormones, and detoxification. The smooth ER is especially abundant in mammalian liver and gonad cells. The ER was observed with light microscope by Garnier in 1897, who coined the term "ergastoplasm". With electron microscopy, the lacy membranes of the endoplasmic reticulum were first seen in 1945 by Keith R. Porter, Albert Claude, Brody Meskers and Ernest F. Fullam. Later, the word "reticulum", which means "network", was applied by Porter in 1953 to describe this fabric of membranes. The

neg: COPI Coat protein, or COPI, is an ADP ribosylation factor (ARF)-dependent protein involved in membrane traffic. COPI was first identified in retrograde traffic from the "cis"-Golgi to the rough endoplasmic reticulum (ER) and is the most extensively studied of ARF-dependent adaptors. COPI consists of seven subunits which compose the heteroheptameric protein complex. The primary function of adaptors is the selection of cargo proteins for their incorporation into nascent carriers. Cargo containing the sorting motifs KKXX and KXKXX interact with COPI to form carriers which are transported from the cis-Golgi to the ER. Current views suggest that ARFs are also involved in

neg: Epoxide hydrolase mEH is widely expressed in virtually all mammalian cells as an endoplasmic reticulum-bound (i.e. microsomal-bound) enzyme with its C terminal catalytic domain facing the cytoplasm; in some tissues, however, mEH has been found bound to the cell surface plasma membrane with its catalytic domain facing the extracellular space. The primary function of mEH is to convert potentially toxic xenobiotics and other compounds that possess epoxide residues (which is often due to their initial metabolism by cytochrome P450 enzymes to epoxides) to diols. Epoxides are highly reactive electrophilic compounds that form adducts with DNA and proteins and also cause strand breaks

neg: Endoplasmic-reticulum-associated protein degradation Endoplasmic-reticulum-associated protein degradation Endoplasmic-reticulum-associated protein degradation (ERAD) designates a cellular pathway which targets misfolded proteins of the endoplasmic reticulum for ubiquitination and subsequent degradation by a protein-degrading complex, called the proteasome. The process of ERAD can be divided into three steps: The recognition of misfolded or mutated proteins depends on the detection of substructures within proteins such as exposed hydrophobic regions, unpaired cysteine residues and immature glycans. In mammalian cells for example, there exists a mechanism called glycan processing. In this mechanism, the lectin-type chaperones calnexin/calreticulin (CNX/CRT) provide immature glycoproteins the opportunity to reach their native conformation. They can do

neg: Wolcott–Rallison syndrome were observed, although these cases are rare. The EIKF2AK3 gene codes for PERK (pancreatic endoplasmic reticulum kinase), an explanation for the spectrum symptoms. PERK is associated with the activity of beta cells in the pancreas. Beta cells are needed for the proper release of insulin into the blood stream after an increase in blood glucose. This kinase is needed for the control of protein levels in the endoplasmic reticulum and is linked to ribosome activity. The endoplasmic reticulum is a major protein sorting and processing center in every cell of the body. A broad range of bodily systems is affected

neg: Hepatocyte to visualise by light microscopy. The hepatocyte is a cell in the body that manufactures serum albumin, fibrinogen, and the prothrombin group of clotting factors (except for Factors 3 and 4). It is the main site for the synthesis of lipoproteins, ceruloplasmin, transferrin, complement, and glycoproteins. Hepatocytes manufacture their own structural proteins and intracellular enzymes. Synthesis of proteins is by the rough endoplasmic reticulum (RER), and both the rough and smooth endoplasmic reticulum (SER) are involved in secretion of the proteins formed. The endoplasmic reticulum (ER) is involved in conjugation of proteins to lipid and carbohydrate moieties synthesized by, or

neg: TIGER domain TIGER domain The TIGER domain is a minor membraneless organelle in which messenger RNA (mRNA) encodes certain types of proteins to find the appropriate environment for growth. It is closely associated with the endoplasmic reticulum during protein synthesis. The TIGER domain was first documented by cell biologists Christine Mayr and Weirui Ma at the Gerstner Sloan Kettering Graduate School of Biomedical Sciences in 2018. The letters TIG stand for TIS granules and letters ER stands for the endoplasmic reticulum. TIS granules form a network of interconnected proteins that bind RNA and the endoplasmic reticulum is where protein synthesis occurs. This

neg: Endoplasmic reticulum the smooth endoplasmic reticulum (abbreviated SER) is scarce. Instead there are areas where the ER is partly smooth and partly rough, this area is called the transitional ER. The transitional ER gets its name because it contains ER exit sites. These are areas where the transport vesicles that contain lipids and proteins made in the ER, detach from the ER and start moving to the Golgi apparatus. Specialized cells can have a lot of smooth endoplasmic reticulum and in these cells the smooth ER has many functions. It synthesizes lipids, phospholipids, and steroids. Cells which secrete these products, such as

neg: ERAP1 ERAP1 Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator, also known as endoplasmic reticulum aminopeptidase 1 (ARTS-1), is a protein which in humans is encoded by the "ARTS-1" gene. Endoplasmic reticulum amino peptidase 1 is active in the endoplasmic reticulum, which is involved in protein processing and transport. This protein is an aminopeptidase, which is an enzyme that cleaves peptides at the N-terminal into smaller fragments called amino acids. ARTS1 is also known as: ERAP1 has two major functions in the immune system: ARTS-1 is a member of the M1 family of zinc metallopeptidases which acts as an aminopeptidase

neg: Derlin-1 Derlin-1 Derlin-1 also known as degradation in endoplasmic reticulum protein 1 is a membrane protein that in humans is encoded by the "DERL1" gene. Derlin-1 is located in the membrane of the endoplasmic reticulum (ER) and is involved in retrotranslocation of specific misfolded proteins and in ER stress. Derlin-1 is widely expressed in thyroid, fat, bone marrow and many other tissues. The protein belongs to the Derlin-family proteins (also called derlins) consisting of derlin-1, derlin-2 and derlin-3 that are components in the endoplasmic reticulum-associated protein degradation (ERAD) pathway. The derlins mediate degradation of misfolded lumenal proteins within ER, and are

neg: Eukaryote a vesicle through exocytosis. The nucleus is surrounded by a double membrane (commonly referred to as a nuclear membrane or nuclear envelope), with pores that allow material to move in and out. Various tube- and sheet-like extensions of the nuclear membrane form the endoplasmic reticulum, which is involved in protein transport and maturation. It includes the rough endoplasmic reticulum where ribosomes are attached to synthesize proteins, which enter the interior space or lumen. Subsequently, they generally enter vesicles, which bud off from the smooth endoplasmic reticulum. In most eukaryotes, these protein-carrying vesicles are released and further modified in stacks of

neg: Endoplasmic reticulum Proteins that are destined for places outside the endoplasmic reticulum are packed into transport vesicles and moved along the cytoskeleton toward their destination. In human fibroblasts, the ER is always co-distributed with microtubules and the depolymerisation of the latter cause its co-aggregation with mitochondria, which are also associated with the ER. The endoplasmic reticulum is also part of a protein sorting pathway. It is, in essence, the transportation system of the eukaryotic cell. The majority of its resident proteins are retained within it through a retention motif. This motif is composed of four amino acids at the end of the

neg: Hepatitis C virus and whose C-terminal has NTPase/helicase activity. It is located within the endoplasmic reticulum and forms a heterodimeric complex with NS4A—a 54 amino acid membrane protein that acts as a cofactor of the proteinase. NS4B is a small (27 kDa) hydrophobic integral membrane protein with 4 transmembrane domains. It is located within the endoplasmic reticulum and plays an important role for recruitment of other viral proteins. It induces morphological changes to the endoplasmic reticulum forming a structure termed the membranous web. NS5A is a hydrophilic phosphoprotein which plays an important role in viral replication, modulation of cell signaling pathways and the

neg: ERAP1 HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin II. Three transcript variants encoding two different isoforms have been found for this gene. ERAP1 Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator, also known as endoplasmic reticulum aminopeptidase 1 (ARTS-1), is a protein which in humans is encoded by the "ARTS-1" gene. Endoplasmic reticulum amino peptidase 1 is active in the endoplasmic reticulum, which is involved

neg: Translocon proteins in the correct orientation into the membrane of the endoplasmic reticulum. The mechanism of this process is not fully understood, but involves the recognition and processing by the translocon of hydrophobic stretches in the amino acid sequence which are destined to become transmembrane helices. Translocators can also move polypeptides (such as damaged proteins targeted for proteasomes) from the cisternal space of the endoplasmic reticulum to the cytosol. ER-proteins are degraded in the cytosol by the 26S proteasome, a process known as Endoplasmic-reticulum-associated protein degradation, and therefore have to be transported by an appropriate channel. This "retrotranslocon" is still enigmatic.

neg: Mahdi Hasan have used this method to study the pattern of rough endoplasmic reticulum in aging CNS neurones. It has been previously noted (Hasan and Glees, 1973) that the highly ordered parallel cistemae of rough endoplasmic reticulum, characteristic of young neurones seem to become dispersed during aging. We have now studied this phenomenon quantitatively. The most surprising finding of the present study is that in both regions (mitral cells of olfactory bulb and cerebellar purkinje cells) studied there occurs a highly linear decrease in the measured closeness of rough endoplasmic reticulum cisternae throughout adult life. Thus we conclude that during aging there

neg: DNA damage-inducible transcript 3 DNA damage-inducible transcript 3 DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a pro-apoptotic transcription factor that is encoded by the "DDIT3" gene. DNA damage-inducible transcript 3 has been shown to interact with [proteins]: During endoplasmic reticulum stress (such as occurs in beta cells of the pancreas or in macrophages causing atherosclerosis), CHOP can induce activation of Ero1, causing calcium release from the endoplasmic reticulum into the cytoplasm, resulting in apoptosis. CHOP also induces apoptosis during endoplasmic reticulum stress by activating growth arrest and DNA damage-inducible protein GADD34. Mutations or fusions of CHOP (e.g. with FUS

neg: FFAT motif proteins with FFAT motifs were previously not known to be targeted to the endoplasmic reticulum, with the exception of OSBP, and PITPNM1 (the fly homologue of which is called RdgB). Instead, they were known for their localization to other sites especially the "trans" Golgi network (OSBP, Osh1p and CERT) and the plasma membrane (Osh2p, Osh3p). The discovery that these proteins also targeted the endoplasmic reticulum led to a far more detailed analysis of their targeting, and revealed that all the FFAT-containing lipid transfer proteins are present at both the endoplasmic reticulum and their other target Trans Golgi network or plasma

neg: Endoplasmic reticulum vesicles to the Golgi apparatus. Correct folding of newly made proteins is made possible by several endoplasmic reticulum chaperone proteins, including protein disulfide isomerase (PDI), ERp29, the Hsp70 family member BiP/Grp78, calnexin, calreticulin, and the peptidylpropyl isomerase family. Only properly folded proteins are transported from the rough ER to the Golgi apparatus – unfolded proteins cause an unfolded protein response as a stress response in the ER. Disturbances in redox regulation, calcium regulation, glucose deprivation, and viral infection or the over-expression of proteins can lead to endoplasmic reticulum stress response (ER stress), a state in which the folding of proteins

neg: Endoplasmic reticulum protein sequence. The most common retention sequences are KDEL for lumen located proteins and KKXX for transmembrane protein. However, variations of KDEL and KKXX do occur, and other sequences can also give rise to endoplasmic reticulum retention. It is not known whether such variation can lead to sub-ER localizations. There are three KDEL (1, 2 and 3) receptors in mammalian cells, and they have a very high degree of sequence identity. The functional differences between these receptors remain to be established. Abnormalities in XBP1 lead to a heightened endoplasmic reticulum stress response and subsequently causes a higher susceptibility for inflammatory

neg: DNA damage-inducible transcript 3 to form FUS-CHOP) can cause Myxoid liposarcoma. DNA damage-inducible transcript 3 DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a pro-apoptotic transcription factor that is encoded by the "DDIT3" gene. DNA damage-inducible transcript 3 has been shown to interact with [proteins]: During endoplasmic reticulum stress (such as occurs in beta cells of the pancreas or in macrophages causing atherosclerosis), CHOP can induce activation of Ero1, causing calcium release from the endoplasmic reticulum into the cytoplasm, resulting in apoptosis. CHOP also induces apoptosis during endoplasmic reticulum stress by activating growth arrest and DNA damage-inducible protein GADD34. Mutations

neg: C-5 sterol desaturase the endoplasmic reticulum and that in "S. cerevisiae" C5SD localizes to both the endoplasmic reticulum and vesicles. In "Arabidopsis thaliana" C5SD is located in both the endoplasmic reticulum and lipid particles. The common class of antifungal drugs known as azoles disrupts the fungal sterol biosynthesis pathway, upstream of C-5 sterol desaturase leading to the accumulation of nontoxic 14α-methylated sterols. C5SD then converts these intermediates into a toxic product. Consequently, in both the pathogenic fungus "Candida albicans" and model organism "S. cerevisiae" mutations in the gene encoding C-5 sterol desaturase (ERG3) allow the cell to avoid synthesizing the toxic sterol products

neg: Endoplasmic reticulum Ribosomes at this point may be released back into the cytosol; however, non-translating ribosomes are also known to stay associated with translocons. The membrane of the rough endoplasmic reticulum forms large double membrane sheets that are located near, and continuous with, the outer layer of the nuclear envelope. The double membrane sheets are stacked and connected through several right or left-handed helical ramps, the so-called Terasaki ramps, giving rise to a structure resembling a multi-storey car park. Although there is no continuous membrane between the endoplasmic reticulum and the Golgi apparatus, membrane-bound transport vesicles shuttle proteins between these two compartments.

neg: Endoplasmic reticulum slows, leading to an increase in unfolded proteins. This stress is emerging as a potential cause of damage in hypoxia/ischemia, insulin resistance, and other disorders. Secretory proteins, mostly glycoproteins, are moved across the endoplasmic reticulum membrane. Proteins that are transported by the endoplasmic reticulum throughout the cell are marked with an address tag called a signal sequence. The N-terminus (one end) of a polypeptide chain (i.e., a protein) contains a few amino acids that work as an address tag, which are removed when the polypeptide reaches its destination. Nascent peptides reach the ER via the translocon, a membrane-embedded multiprotein complex.

neg: Jennifer Lippincott-Schwartz Lippincott-Schwartz utilized advanced imaging techniques to reveal a more accurate picture of how the peripheral endoplasmic reticulum is structured. Their findings may yield new insights for genetic diseases affecting proteins that help shape the endoplasmic reticulum. Additionally, Lippincott-Schwartz's laboratory demonstrated that Golgi enzymes constitutively recycle back to the endoplasmic reticulum and that such recycling plays a central role in the maintenance, biogenesis, and inheritance of the Golgi apparatus in mammalian cells. Within Lippincott-Schwartz lab, current projects include several cell biological areas. For example, protein transport and cytoskeleton interaction, organelle assembly and disassembly, and cell polarity generation. There are also projects

neg: Endoplasmic reticulum resident protein signal retention. Endoplasmic reticulum resident protein ER retention refers to proteins that are retained in the endoplasmic reticulum, or ER, after folding; these are known as ER resident proteins. Their localization to the ER often depends on certain sequences of amino acids located at the N-terminus or C-terminus. The classical ER retention signal is the C-terminal KDEL sequence for lumen bound proteins and KKXX for transmembrane localization. These signals allow for retrieval from the Golgi apparatus by ER retention receptors, effectively maintaining the protein in the ER. Other mechanisms for ER retention are being studied but are not as well

neg: Endoplasmic reticulum resident protein Endoplasmic reticulum resident protein ER retention refers to proteins that are retained in the endoplasmic reticulum, or ER, after folding; these are known as ER resident proteins. Their localization to the ER often depends on certain sequences of amino acids located at the N-terminus or C-terminus. The classical ER retention signal is the C-terminal KDEL sequence for lumen bound proteins and KKXX for transmembrane localization. These signals allow for retrieval from the Golgi apparatus by ER retention receptors, effectively maintaining the protein in the ER. Other mechanisms for ER retention are being studied but are not as well characterized as

neg: Sarcoplasm inside the cell membrane (sarcolemma), and a smooth endoplasmic reticulum (specialized for muscle function and called the sarcoplasmic reticulum). While "sarcoplasm" and "myoplasm," viewed etymologically, might seem to be synonyms, they are not. Whereas sarcoplasm is a type of cytoplasm, myoplasm is the entire contractile portion of muscle tissue. Sarcoplasm Sarcoplasm is the cytoplasm of a myocyte (muscle fiber). It is comparable to the cytoplasm of other cells, but it contains unusually large amounts of "glycosomes" (granules of stored glycogen) and significant amounts of myoglobin, an oxygen-binding protein. The calcium ion concentration in sarcoplasma is also a special element of

neg: Endoplasmic reticulum membrane protein complex pathologies seem to be related by disruption of a single molecular pathway that might be regulated by the mEMC. Consequently, the involvement of the mEMC in these pathologies has only limited use for defining the primary function of this complex. Large-scale genetic screens imply several mEMC subunits in modulating the pathogenicity of flaviviruses such as West Nile Virus (WNV), Zika Virus (ZV), Dengue Fever Virus (DFV), and Yellow Fever Virus (YFV). In particular, loss of several mEMC subunits (e.g. EMC2, EMC3) lead to inhibition of WNV-induced cell death. however, WNV was still able to infect and proliferate in cells lacking

neg: Ryanodine receptor from the sarcoplasmic reticulum and endoplasmic reticulum, an essential step in muscle contraction. In skeletal muscle, activation of ryanodine receptors occurs via a physical coupling to the dihydropyridine receptor (a voltage-dependent, L-type calcium channel), whereas, in cardiac muscle, the primary mechanism of activation is calcium-induced calcium release, which causes calcium outflow from the sarcoplasmic reticulum. It has been shown that calcium release from a number of ryanodine receptors in a ryanodine receptor cluster results in a spatiotemporally restricted rise in cytosolic calcium that can be visualised as a "calcium spark". Ryanodine receptors are very close to mitochondria and calcium release

neg: Phosphodiesterase 3 isoforms, and the N-terminal portions of the isoforms are quite divergent. PDE3A and PDE3B have strikingly similar pharmacological and kinetic properties, but the distinction is in expression profiles and affinity for cGMP. PDE3A is mainly implicated in cardiovascular function and fertility but PDE3B is mainly implicated in lipolysis. Table 1 is an overview of localization of the PDE3 isoforms. In general, PDE3 can be either cytosolic or membrane-bound and has been associated to plasma membrane, sarcoplasmic reticulum, golgi, and nucleus envelope. PDE3B is predominantly membrane-associated, and is localized to endoplasmic reticulum and microsomal fractions. PDE3A can be either membrane-associated or

neg: Ribophorin Ribophorin Ribophorins are transmembrane glycoproteins which are located in the membrane of the rough endoplasmic reticulum, but are absent in the membrane of the smooth endoplasmic reticulum. There are two types of ribophorines: ribophorin I and II. These act in the proteic complex oligosaccharyltransferase (OST) as two different subunits of the named complex. Ribophorin I and II are only present in eukaryote cells. Both types of ribophorins develop a key role in the binding of ribosomes to the rough endoplasmic reticulum as well as in the co-translational processes that depend on this interaction. The content of ribophorin of the rough

neg: Ribophorin acids, respectively. Ribophorin Ribophorins are transmembrane glycoproteins which are located in the membrane of the rough endoplasmic reticulum, but are absent in the membrane of the smooth endoplasmic reticulum. There are two types of ribophorines: ribophorin I and II. These act in the proteic complex oligosaccharyltransferase (OST) as two different subunits of the named complex. Ribophorin I and II are only present in eukaryote cells. Both types of ribophorins develop a key role in the binding of ribosomes to the rough endoplasmic reticulum as well as in the co-translational processes that depend on this interaction. The content of ribophorin of

neg: Tom Rapoport the United States, the country his parents fled from in 1950, in 1995. He has been a professor at the Harvard Medical School since 1995, and an HHMI investigator since 1997. He studies several aspects of cellular secretion, including the mechanisms by which newly synthesized proteins are translocated from the cytosol to the lumen of the endoplasmic reticulum by the Sec61 complex (also known as the translocon), how misfolded secretory proteins are degraded by endoplasmic reticulum associated protein degradation (also known as ERAD), and how reticulons and related proteins regulate the morphology of the endoplasmic reticulum. Tom Rapoport Tom Abraham

neg: Inositol-trisphosphate 3-kinase (DAG) and inositol 1,4,5-trisphosphate (IP). DAG remains associated with the plasma membrane, while IP is released into the cytoplasm. IP then diffuses through the cytosol and binds to IP receptors on the endoplasmic reticulum or sarcoplasmic reticulum, resulting in the opening of a membrane channel and an influx of calcium ions into the cytoplasm. Calcium serves as a second messenger for various downstream cellular events including glycogen metabolism, muscle contraction, neurotransmitter release, and transcriptional regulation. Therefore, calcium homeostasis is essential for proper cell function and response to extracellular signals. In order to prepare the cell for a future signaling event,

neg: Endoplasmic reticulum stress in beta cells Endoplasmic reticulum stress in beta cells Beta cells are heavily engaged in the synthesis and secretion of insulin. They are therefore particularly sensitive to endoplasmic reticulum (ER) stress and the subsequent unfolded protein response (UPR). Severe or prolonged episodes of ER stress can lead to the death of beta cells, which can contribute to the development of diabetes. ER stress can be activated by a variety of factors. In experimental conditions, excessive lipid (which can happen following obesity, a common condition preceding type 2 diabetes) and pro-inflammatory cytokines (which can occur following an inflammation, a common cause for type 1

neg: Endomembrane system proteins, which become embedded in the membrane of the endoplasmic reticulum, or water-soluble proteins, which are able to pass through the membrane into the lumen. Those that reach the inside of the endoplasmic reticulum are folded into the correct three-dimensional conformation. Chemicals, such as carbohydrates or sugars, are added, then the endoplasmic reticulum either transports the completed proteins, called secretory proteins, to areas of the cell where they are needed, or they are sent to the Golgi apparatus for further processing and modification. Once secretory proteins are formed, the ER membrane separates them from the proteins that will remain in

neg: Dyadic space (cell biology) Dyadic space (cell biology) The dyadic space is the name for the volume of cytoplasm between pairs (dyads) of areas where the cell membrane and an organelle such as the endoplasmic reticulum (or sarcoplasmic reticulum) come into close contact (within 10-12 nanometers) of each other, creating what are known as "dyadic clefts". The space is important for ionic signalling. For example, the phenomenon of "calcium-induced calcium release", when extracellular calcium enters the cell through ion channels in T-Tubules, leading to a rapidly increased calcium concentration in the dyadic space, triggering ryanodine receptors on the sarcoplasmic reticulum to release more calcium

neg: Cranio–lenticulo–sutural dysplasia bound carrying compartment for molecules) containing a secretory protein destined for packaging in the Golgi apparatus of the cell. Uncoating the vesicle exposes SNARE proteins which are needed for the vesicle to bind to the membrane site on the endoplasmic reticulum. A mutation in the SEC23A gene prevents the vesicle from uncoating so it will not bind to the receptor site on the endoplasmic reticulum to be released into the cytoplasm for transport to the Golgi apparatus. Thus, the vesicles will accumulate in the endoplasmic reticulum, causing it to become enlarged or distended. Ultimately, this causes the craniofacial symptoms present

neg: Chaperone (protein) membranes of the mitochondria and endoplasmic reticulum (ER) in eukaryotes. Bacterial translocation—specific chaperone maintains newly synthesized precursor polypeptide chains in a translocation-competent (generally unfolded) state and guides them to the translocon. New functions for chaperones continue to be discovered, such as assistance in protein degradation, bacterial adhesin activity, and in responding to diseases linked to protein aggregation (e.g. see prion) and cancer maintenance. Chaperones are found in, for example, the endoplasmic reticulum (ER), since protein synthesis often occurs in this area. In the endoplasmic reticulum (ER) there are general, lectin- and non-classical molecular chaperones helping to fold proteins. There are

neg: Sodium-chloride symporter of mutations exist within the group of missense mutations causing loss of NCC function. Type I mutations cause a complete loss of NCC function, in which the synthesized protein is not properly glycosylated. NCC protein harboring type I mutations is retained in the endoplasmic reticulum and cannot be trafficked to the cell surface. Type II mutations cause a partial loss of NCC function in which the cotransporter is trafficked to the cell surface but has an impaired insertion in the plasma membrane. NCC harboring type II mutations have normal kinetic properties but are present in lower amounts at the cell

neg: TIGER domain combination of the TIS proteins and the endoplasmic reticulum creates a distinct place in which mRNA and proteins collect, interact, and grow. The striped pattern of the TIS granules that are interweaving with the endoplasmic reticuum also resemble the orange and black stripes of a tiger. The TIGER domain has been found in all types of cells scientists have looked at so far. TIGER domain The TIGER domain is a minor membraneless organelle in which messenger RNA (mRNA) encodes certain types of proteins to find the appropriate environment for growth. It is closely associated with the endoplasmic reticulum during protein

neg: Calcium-induced calcium release of CICR across the cell causes the significant increase in cytosolic Ca that is important in activating muscle contraction. Calcium-induced calcium release Calcium-induced calcium release (CICR) describes a biological process whereby calcium is able to activate calcium release from intracellular Ca stores (e.g., endoplasmic reticulum or sarcoplasmic reticulum). Although CICR was first proposed for skeletal muscle in the 1970s, it is now known that CICR is unlikely to be its primary mechanism for activating SR calcium release. Instead, CICR is thought to be crucial for excitation-contraction coupling in cardiac muscle and it is now obvious that CICR is a widely

neg: Congenital hypofibrinogenemia respectively). The genes are ordered "FGB, FGA," and "FGG" and are transcribed into messenger RNA in tight synchrony. The messenger RNAs associate with the endoplasmic reticulum, translated into polypeptides, and enter the endoplasmaic reticulum where they assembled together. The assembled protein is passes to the Golgi apparatus where it is glycosylated, hydroxylated, sulfated, and phosphorylated to form the mature fibrinogen glycoprotein that is secreted into the blood. Congenital hypfibrinogenemia results from inherited mutations in one of the three fibrinogen chains that results in the disruption of fibrinogen synthesis, assembly, stability, processing through the endoplasmic reticulum-Golgi apparatus pathway, and/or secretion into

neg: Calcium-induced calcium release Calcium-induced calcium release Calcium-induced calcium release (CICR) describes a biological process whereby calcium is able to activate calcium release from intracellular Ca stores (e.g., endoplasmic reticulum or sarcoplasmic reticulum). Although CICR was first proposed for skeletal muscle in the 1970s, it is now known that CICR is unlikely to be its primary mechanism for activating SR calcium release. Instead, CICR is thought to be crucial for excitation-contraction coupling in cardiac muscle and it is now obvious that CICR is a widely occurring cellular signaling process present even in many non-muscle cells, e.g. in the insulin-secreting pancreatic beta cells and many

neg: Cortical granule Researchers also hypothesize the oocyte releases some cortical granules pre-fertilzation in order to make minor modifications to the oocyte's extracellular matrix so that binding is limited to only sperm capable of binding despite these minor modifications. Following fertilization and prior to the calcium release, an inositol phosphate (PIP2) signaling cascade is initiated. Throughout this process, second messenger molecules such as, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), increase in concentration. Inositol 1,4,5-trisphosphate has been shown to interact with the endoplasmic reticulum causing the release of the endoplasmic reticulum's calcium stores. Further emphasizing the relationship between the endoplasmic reticulum and cortical granules,

neg: Granzyme Granzyme Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are infected with viruses or bacteria. Granzymes also kill bacteria and inhibit viral replication. In NK cells and T cells, granzymes are packaged in cytotoxic granules with perforin. Granzymes can also be detected in the rough endoplasmic reticulum, golgi complex, and the trans-golgi reticulum. The contents of the cytotoxic granules function to permit entry of the granzymes into the target cell cytosol. The granules

neg: Calcium signaling reticulum (ER), and sometimes into the mitochondria. Certain proteins of the cytoplasm and organelles act as buffers by binding Ca. Signaling occurs when the cell is stimulated to release Ca ions from intracellular stores, and/or when Ca enters the cell through plasma membrane ion channels. Specific signals can trigger a sudden increase in the cytoplasmic Ca level up to 500–1,000 nM by opening channels in the endoplasmic reticulum or the plasma membrane. The most common signaling pathway that increases cytoplasmic calcium concentration is the phospholipase C pathway. Depletion of Ca from the endoplasmic reticulum will lead to Ca entry from

neg: CCDC47 CCDC47 Coiled-coil domain 47 (CCDC47) is a gene located on human chromosome 17, specifically locus 17q23.3 which encodes for the protein CCDC47. The gene has several aliases including GK001 and MSTP041. The protein itself contains coiled-coil domains, the SEEEED superfamily, a domain of unknown function (DUF1682) and a transmembrane domain. The function of the protein is unknown, but it has been proposed that CCDC47 is involved in calcium ion homeostasis and the endoplasmic reticulum overload response. The CCDC47 gene itself is located on the minus strand of human chromosome 17 and contains 13 exon splice sites and 14 distinct introns.

neg: VAPA neurons observed in such condition could to be due to the inability of VAPB to regulate the lipid function around the ER and the subsequent consequences on cell function. VAPA VAMP-Associated Protein A ( or Vesicle-Associated Membrane Protein-Associated Protein A) is a protein that in humans is encoded by the "VAPA" gene. Together with VAPB and VAPC it forms the VAP protein family. They are integral endoplasmic reticulum membrane proteins of the type II and are ubiquitous among eukaryotes. VAPA is ubiquitously expressed in human tissues and is thought to be involved in membrane trafficking by interaction with SNAREs. in

neg: SEP15 have redox function and may be involved in the quality control of protein folding. This gene is localized on chromosome 1p31, a genetic locus commonly mutated or deleted in human cancers. The protein this gene encodes for is often called Sep15 however in the case of mice, it is named SelM. This protein is an selenoprotein only found in eukaryotes. This domain has a thioredoxin-like domain and a surface accessible active site redox motif. This suggests that they function as thiol-disulfide isomerases involved in disulfide bond formation in the endoplasmic reticulum. Recent studies have shown in mice, where the SEP15

neg: FAM210B be as shown below. The primary location of the FAM210B protein is the endoplasmic reticulum. The amino acid sequence contains the endoplasmic retention signal PAAK near the C-terminus. There are 2 transmembrane domains, which have been determined and reaffirmed by multiple methods. They are highlighted in the post-translational modification image below. The following conceptual translation presents expected post-translational modifications. The modifications were predicted by MotifScan, and then searched in greater detail in Expasy Modifications found include propeptide cleavage sites, C-mannosylation sites, GalNAc O-glycosylation sites, lysine glycation sites, phosphorylation sites, a Coronavirus 3C-like proteinase cleavage site, and a GPI modification site.

neg: PCK2 while PCK1 expression is regulated by hormones or nutrients involved in gluconeogenesis, PCK2 is constitutively expressed. These differences indicate that PCK2 may also perform non-gluconeogenic functions. PCK2 is associated with several cancers, including lung cancer, and promotes tumorigenesis through its gluconeogenic function. In low-glucose settings, stress to the endoplasmic reticulum upregulates ATF4, which then upregulates PCK2. As PCK2 allows cells to utilize alternative cataplerotic pathways to convert TCA cycle intermediates to glycolytic intermediates, PCK2 activity can enhance the survival tumor cells facing reduced glucose levels. Due to the gluconeogenic function of PCK2, PCK2 deficiency is expected to disrupt glucose homeostasis

neg: PBDC1 KKXX-like motif, QDKE, is found to exist at the end of the domain. The K in this motif is highly conserved back to most invertebrates. However, contradicting results from NetNGlyc predicted no N-glycosylation sites, suggesting CXorf26 does not undergo special folding in the endoplasmic reticulum lumen. Given that the conserved domain cannot function to create xylan since there are no cell walls in animal cells, the function may be related to this pathway. Predictions across multiple programs suggest the presence of 7 alpha helices and 2 beta sheets for CXorf26; the majority of the secondary structures are in the conserved

neg: Durinskia four membrane. These red plastids also contain peridinin, a major carotenoid pigment specific to dinoflagellates. In "Durinskia", the function of the secondary red plastid is replaced by incorporating a diatom and its diatom’s plastid as a tertiary endosymbiont. The diatom-derived tertiary plastid in "Durinskia" is not as reduced as other plastids where the secondary host components are completely reduced and only the plastid remains. In addition to retaining the nuclear genome and the large nucleus of the diatom, the diatom’s mitochondria and mitochondrial genome, cytosolic ribosomes, and endoplasmic reticulum are retained. However, the diatom can no longer function as a

neg: Transmembrane protein 134 which is conserved throughout the different orthologs. The protein also contains a domain of unknown function 872 (DUF872). Currently there is no thought to the possible function of this domain. TMEM134 is regulated by the promoter GXP50275. There are 870 amino acids in the promoter and 15 transcripts variants of it. The promoter is well conserved in mammals. There are some conserved binding regions in the promoter including EGR/nerve factor and Huntington's disease gene regulatory region. The final protein is thought to be in the endoplasmic reticulum and the nuclear membrane. The protein is anchored in two different regions, from

neg: FKBP7 FKBP7 FK506 binding protein 7 is a protein that in humans is encoded by the "FKBP7" gene. The gene is also known as "FKBP23" and "PPIase". FKBP7 belongs to the FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) family. Members of this family exhibit PPIase activity and function as molecular chaperones. The orthologous protein in mouse is located in the endoplasmic reticulum and binds calcium. Model organisms have been used in the study of FKBP7 function. A conditional knockout mouse line, called "Fkbp7" was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute

neg: MSR1 classes, too. The isoforms type 1 and type 2 are functional receptors and are able to mediate the endocytosis of modified low density lipoproteins (LDLs). The isoform type 3 does not internalize modified LDL (acetyl-LDL) despite having the domain shown to mediate this function in the types 1 and 2 isoforms. It has an altered intracellular processing and is trapped within the endoplasmic reticulum, making it unable to perform endocytosis. The isoform type 3 can inhibit the function of isoforms type 1 and type 2 when co-expressed, indicating a dominant negative effect and suggesting a mechanism for regulation of scavenger

neg: ERGIC2 being a component of a protein trafficking shuttle. More recently, a variant transcript of ERGIC2 has been reported. It has a deletion of four bases at the junction of exons 8 and 9, resulting a frame-shift mutation after codon #189. The variant transcript encodes a truncated protein of 215 residues, which loses 45% of the luminal domain and the transmembrane domain near the C-terminus. This effectively abrogates its function as a protein transporter. A similar variant is also reported in armadillo. So this is not a random mutation. The function of this truncated protein is unknown. ERGIC2 Endoplasmic reticulum-Golgi intermediate

neg: Endoplasmic-reticulum-associated protein degradation recognized by different mechanisms. This led to the identification of 3 different pathways that constitute in fact 3 checkpoints. As ERAD is a central element of the secretory pathway, disorders in its activity can cause a range of human diseases. These disorders can be classified into two groups. The first group is the result of mutations in ERAD components, which subsequently lose their function. By losing their function, these components are no longer able to stabilize aberrant proteins, so that the latter accumulate and damage the cell. An example of a disease caused by this first group of disorders is

neg: Epoxide hydrolase of LTA4AH is unknown but has been proposed to be involved in limiting inflammatory reactions caused by this or other aminopeptidase-susceptible peptides. (Cholesterol epoxide hydrolase or ChEH), is located in the endoplasmic reticulum and to a lesser extent plasma membrane of various cell types but most highly express in liver. The enzyme catalyzes the conversion of certain 3-hydoxyl-5,6-epoxides of cholesterol to their 3,5,6-trihydroxy products (see Cholesterol-5,6-oxide hydrolase). The function of ChEH is unknown. The substrate(s) and physiological function of Peg1/MEST are not known; however, the protein may play a role in mammalian development and abnormalities in its expression by its

neg: Endoplasmic reticulum membrane protein complex could form a β-propeller domain. The TMD is part of a domain a larger domain (DUF1620). The functions of the PQQ and DUF1620 domains in EMC1 remain to be determined. EMC2 (TTC35) harbours three tetratricopeptide repeats (TPR1/2/3). TPRs have been shown to mediate protein-protein interactions and can be found in a large variety of proteins of diverse function. The function of TPRs in EMC2 is unknown. EMC8 and EMC9 show marked sequence identity (44.72%) on the amino acid level. Both proteins are members of the UPF0172 family, a member of which (e.g. TLA1) are unvolved in regulating the antenna size

neg: Integrin-linked kinase showed that the C-terminal kinase domain is actually a pseudo-kinase with adaptor function. In 2008, ILK was found to localize to the centrosome and regulate mitotic spindle organization. Integrin-linked kinase has been shown to interact with: ILKs function by interacting with the many transmembrane receptors to regulate different signaling cascades. ILK1 has been found in the root system of most plants where they are co-localized on the plasma membrane and endoplasmic reticulum where they transport ions across the plasma membrane ILK1 is responsible for the control of osmotic and salt stress, control of the uptake of nutrients based on availability

neg: Calreticulin Calreticulin binds to misfolded proteins and prevents them from being exported from the endoplasmic reticulum to the Golgi apparatus. A similar quality-control molecular chaperone, calnexin, performs the same service for soluble proteins as does calreticulin, however it is a membrane-bound protein. Both proteins, calnexin and calreticulin, have the function of binding to oligosaccharides containing terminal glucose residues, thereby targeting them for degradation. Calreticulin and Calnexin's ability to bind carbohydrates associates them with the lectin protein family. In normal cellular function, trimming of glucose residues off the core oligosaccharide added during N-linked glycosylation is a part of protein processing. If "overseer"

neg: Cranio–lenticulo–sutural dysplasia who were affected inherited the defective gene from both of their parents (Boyadjiev, 1193). A Caucasian male was also found to have symptoms of the disease, but possessed only one defective chromosome. Measurements of the endoplasmic reticulums of his mother and father showed that the mother had a normal phenotype, the father had a slightly distended endoplasmic reticulum, and the affected son had an endoplasmic reticulum distended to a much greater extent. Because of the normal measurements obtained from the mother, it was concluded that the father was responsible for the son's symptoms and was hypothesized that there was another

neg: Raymond J. Deshaies post-translational insertion of proteins into the endoplasmic reticulum and mitochondrial membranes. This was the first specific, genetically- and biochemically-validated function to be discovered for a member of the Hsp70 family of proteins. SCF and cullin–RING ubiquitin ligases: As a postdoctoral fellow working with Dr. Marc Kirschner at the University of California, San Francisco, Deshaies discovered a biochemical function for the ubiquitin-conjugated enzyme CDC34, which he showed mediates conjugation of ubiquitin onto G1 cyclin proteins in yeast cells. Upon starting his laboratory at Caltech, Deshaies studied the function of Cdc34 and how it relates to progression through the cell division cycle.