2ROP , 2EW9 , 2KOY , 2LQB
43-398: 540 11979 ENSG00000123191 ENSMUSG00000006567 P35670 Q64446 NM_000053 NM_001005918 NM_001243182 NM_001330578 NM_001330579 NM_007511 NP_000044.2 NP_000044.2 NP_001005918.1 NP_001230111.1 NP_031537 NP_001390638 Wilson disease protein ( WND ), also known as ATP7B protein , is a copper-transporting P-type ATPase which
86-530: A cis entry face and a trans exit face. These faces are characterized by unique morphology and biochemistry . Within individual stacks are assortments of enzymes responsible for selectively modifying protein cargo. These modifications influence the fate of the protein. The compartmentalization of the Golgi apparatus is advantageous for separating enzymes, thereby maintaining consecutive and selective processing steps: enzymes catalyzing early modifications are gathered in
129-418: A phosphorylation site, and at least two putative copper -binding sites. This protein functions as a monomer, exporting copper out of the cells, such as the efflux of hepatic copper into the bile . Alternate transcriptional splice variants , encoding different isoforms with distinct cellular localizations, have been characterized. Wilson's disease is caused by various mutations . One of the common mutations
172-436: A signal sequence that determines the final destination of the protein. For example, the Golgi apparatus adds a mannose-6-phosphate label to proteins destined for lysosomes. Another important function of the Golgi apparatus is in the formation of proteoglycans . Enzymes in the Golgi append proteins to glycosaminoglycans , thus creating proteoglycans. Glycosaminoglycans are long unbranched polysaccharide molecules present in
215-404: A high affinity to other transition metal ions such as zinc Zn(II), cadmium Cd(II), gold Au(III), and mercury Hg(II). However, copper is able to decrease the zinc binding affinity at low concentration and increase copper binding affinity dramatically with increasing concentration to ensure a strong binding between the motif and copper. As a P-type ATPases , ATP7B undergoes auto- phosphorylation of
258-411: A hydrogen acceptor in a chain of ATP synthase. Dietary L-aspartic acid has been shown to act as an inhibitor of Beta-glucuronidase , which serves to regulate enterohepatic circulation of bilirubin and bile acids. Click on genes, proteins and metabolites below to link to respective articles. Aspartate (the conjugate base of aspartic acid) stimulates NMDA receptors , though not as strongly as
301-450: A key conserved aspartic acid (D) residue in the DKTGT motif. The ATP binding to the protein initiates the reaction and copper binds to the transmembrane region. Then phosphorylation occurs at the aspartic acid residue in the DKTGT motif with Cu release. Then dephosphorylation of the aspartic acid residue recovers the protein to ready for the next transport. Most of ATP7B protein is located in
344-423: A mixture of two. Of these two forms, only one, " L -aspartic acid", is directly incorporated into proteins. The biological roles of its counterpart, " D -aspartic acid" are more limited. Where enzymatic synthesis will produce one or the other, most chemical syntheses will produce both forms, " DL -aspartic acid", known as a racemic mixture . In the human body, aspartate is most frequently synthesized through
387-400: Is biodegradable superabsorbent polymers (SAP), and hydrogels. Around 75% of superabsorbent polymers are used in disposable diapers and an additional 20% is used for adult incontinence and feminine hygiene products. Polyaspartic acid , the polymerization product of aspartic acid, is a biodegradable substitute to polyacrylate . In addition to SAP, aspartic acid has applications in
430-427: Is a metabolite in the urea cycle and participates in gluconeogenesis . It carries reducing equivalents in the malate-aspartate shuttle , which utilizes the ready interconversion of aspartate and oxaloacetate , which is the oxidized (dehydrogenated) derivative of malic acid . Aspartate donates one nitrogen atom in the biosynthesis of inosine , the precursor to the purine bases. In addition, aspartic acid acts as
473-455: Is associated with ATP7B gene , approximately 80 Kb, located on human chromosome 13 and consists of 21 exons. The mRNA transcribed by ATP7B gene has a size of 7.5 Kb, and which encodes a protein of 1465 amino acids . The gene is a member of the P-type cation transport ATPase family and encodes a protein with several membrane-spanning domains, an ATPase consensus sequence , a hinge domain,
SECTION 10
#1732895315085516-510: Is encoded by the ATP7B gene. The ATP7B protein is located in the trans-Golgi network of the liver and brain and balances the copper level in the body by excreting excess copper into bile and plasma. Genetic disorder of the ATP7B gene may cause Wilson's disease , a disease in which copper accumulates in tissues, leading to neurological or psychiatric issues and liver diseases . Wilson disease protein
559-478: Is incorporated into some peptides and plays a role as a neurotransmitter / neuromodulator . Like all other amino acids, aspartic acid contains an amino group and a carboxylic acid. Its α-amino group is in the protonated –NH 3 form under physiological conditions, while its α-carboxylic acid group is deprotonated −COO under physiological conditions. Aspartic acid has an acidic side chain (CH 2 COOH) which reacts with other amino acids, enzymes and proteins in
602-472: Is not observed. Pichia pastoris does have stacked Golgi, while Saccharomyces cerevisiae does not. In plants, the individual stacks of the Golgi apparatus seem to operate independently. The Golgi apparatus tends to be larger and more numerous in cells that synthesize and secrete large amounts of substances; for example, the antibody -secreting plasma B cells of the immune system have prominent Golgi complexes. In all eukaryotes, each cisternal stack has
645-498: Is single base pair mutation, H1069Q. ATP7B protein is a copper-transporting P-type ATPase , synthesized as a membrane protein of 165 KDa in human hepatoma cell line, and which is 57% homologous to Menkes disease -associated protein ATP7A . ATP7B consists of several domains : The CPC motif (Cys-Pro-Cys) in transmembrane segment 6 characterizes the protein as a heavy metal transporting ATPase . The copper binding motif also shows
688-495: Is the first cisternal structure, and the TGN is the final, from which proteins are packaged into vesicles destined to lysosomes , secretory vesicles, or the cell surface. The TGN is usually positioned adjacent to the stack, but can also be separate from it. The TGN may act as an early endosome in yeast and plants. There are structural and organizational differences in the Golgi apparatus among eukaryotes. In some yeasts, Golgi stacking
731-490: Is the malfunction of ATP7B by single base pair mutations, deletions, frame-shifts, splice errors in ATP7B gene. Trans-Golgi network The Golgi apparatus ( / ˈ ɡ ɒ l dʒ i / ), also known as the Golgi complex , Golgi body , or simply the Golgi , is an organelle found in most eukaryotic cells . Part of the endomembrane system in the cytoplasm , it packages proteins into membrane-bound vesicles inside
774-483: Is the precursor to several amino acids, including four that are essential for humans: methionine , threonine , isoleucine , and lysine . The conversion of aspartate to these other amino acids begins with reduction of aspartate to its "semialdehyde", O 2 CCH(NH 2 )CH 2 CHO. Asparagine is derived from aspartate via transamidation: (where G C(O)NH 2 and G C(O)OH are glutamine and glutamic acid , respectively) Aspartate has many other biochemical roles. It
817-491: The cis face cisternae, and enzymes catalyzing later modifications are found in trans face cisternae of the Golgi stacks. The Golgi apparatus is a major collection and dispatch station of protein products received from the endoplasmic reticulum. Proteins synthesized in the ER are packaged into vesicles, which then fuse with the Golgi apparatus. These cargo proteins are modified and destined for secretion via exocytosis or for use in
860-410: The extracellular matrix of animals. The vesicles that leave the rough endoplasmic reticulum are transported to the cis face of the Golgi apparatus, where they fuse with the Golgi membrane and empty their contents into the lumen . Once inside the lumen, the molecules are modified, then sorted for transport to their next destinations. Those proteins destined for areas of the cell other than either
903-493: The fertilizer industry , where polyaspartate improves water retention and nitrogen uptake. Aspartic acid is not an essential amino acid , which means that it can be synthesized from central metabolic pathway intermediates in humans, and does not need to be present in the diet. In eukaryotic cells, roughly 1 in 20 amino acids incorporated into a protein is an aspartic acid, and accordingly almost any source of dietary protein will include aspartic acid. Additionally, aspartic acid
SECTION 20
#1732895315085946-463: The signal sequence they carry. Though there are multiple models that attempt to explain vesicular traffic throughout the Golgi, no individual model can independently explain all observations of the Golgi apparatus. Currently, the cisternal progression/maturation model is the most accepted among scientists, accommodating many observations across eukaryotes. The other models are still important in framing questions and guiding future experimentation. Among
989-447: The trans-Golgi network (TGN) of hepatocytes , which is different from its homologous protein ATP7A. Small amount of ATP7B is located in the brain . As a copper-transporting protein, one major function is delivering copper to copper dependent enzymes in Golgi apparatus (e.g. holo-ceruloplasmin (CPN)). In the human body, the liver plays an important role in copper regulation including removal of extra copper. ATP7B participates in
1032-525: The transamination of oxaloacetate . The biosynthesis of aspartate is facilitated by an aminotransferase enzyme: the transfer of an amine group from another molecule such as alanine or glutamine yields aspartate and an alpha-keto acid. Industrially, aspartate is produced by amination of fumarate catalyzed by L- aspartate ammonia-lyase . Racemic aspartic acid can be synthesized from diethyl sodium phthalimidomalonate, (C 6 H 4 (CO) 2 NC(CO 2 Et) 2 ). In plants and microorganisms , aspartate
1075-510: The Golgi–Holmgren apparatus, Golgi–Holmgren ducts, and Golgi–Kopsch apparatus. The term Golgi apparatus was used in 1910 and first appeared in scientific literature in 1913, while "Golgi complex" was introduced in 1956. The subcellular localization of the Golgi apparatus varies among eukaryotes. In mammals, a single Golgi apparatus is usually located near the cell nucleus, close to the centrosome. Tubular connections are responsible for linking
1118-479: The Italian biologist and pathologist Camillo Golgi . The organelle was later named after him in the 1910s. Because of its large size and distinctive structure, the Golgi apparatus was one of the first organelles to be discovered and observed in detail. It was discovered in 1898 by Italian physician Camillo Golgi during an investigation of the nervous system . After first observing it under his microscope , he termed
1161-822: The N-termini of alpha helices . Aspartic acid, like glutamic acid , is classified as an acidic amino acid, with a pK a of 3.9; however, in a peptide this is highly dependent on the local environment, and could be as high as 14. The one-letter code D for aspartate was assigned arbitrarily, with the proposed mnemonic aspar D ic acid. Aspartic acid was first discovered in 1827 by Auguste-Arthur Plisson and Étienne Ossian Henry by hydrolysis of asparagine , which had been isolated from asparagus juice in 1806. Their original method used lead hydroxide , but various other acids or bases are now more commonly used instead. There are two forms or enantiomers of aspartic acid. The name "aspartic acid" can refer to either enantiomer or
1204-478: The amino acid neurotransmitter L-glutamate does. In 2014, the global market for aspartic acid was 39.3 thousand short tons (35.7 thousand tonnes ) or about $ 117 million annually. The three largest market segments include the U.S., Western Europe, and China. Current applications include biodegradable polymers ( polyaspartic acid ), low calorie sweeteners ( aspartame ), scale and corrosion inhibitors, and resins. One area of aspartic acid market growth
1247-399: The binding of COPs to endosomes and the Golgi. BFA inhibits the function of several guanine nucleotide exchange factors (GEFs) that mediate GTP-binding of ARFs. Treatment of cells with BFA thus disrupts the secretion pathway, promoting disassembly of the Golgi apparatus and distributing Golgi proteins to the endosomes and ER. Aspartic acid Aspartic acid (symbol Asp or D ;
1290-405: The body. Under physiological conditions (pH 7.4) in proteins the side chain usually occurs as the negatively charged aspartate form, −COO . It is a non- essential amino acid in humans, meaning the body can synthesize it as needed. It is encoded by the codons GAU and GAC. In proteins aspartate sidechains are often hydrogen bonded to form asx turns or asx motifs , which frequently occur at
1333-403: The cell before the vesicles are sent to their destination. It resides at the intersection of the secretory, lysosomal, and endocytic pathways. It is of particular importance in processing proteins for secretion , containing a set of glycosylation enzymes that attach various sugar monomers to proteins as the proteins move through the apparatus. The Golgi apparatus was identified in 1898 by
Wilson disease protein - Misplaced Pages Continue
1376-486: The cell. In this respect, the Golgi can be thought of as similar to a post office: it packages and labels items which it then sends to different parts of the cell or to the extracellular space . The Golgi apparatus is also involved in lipid transport and lysosome formation. The structure and function of the Golgi apparatus are intimately linked. Individual stacks have different assortments of enzymes, allowing for progressive processing of cargo proteins as they travel from
1419-503: The centrosomal region and do not form Golgi ribbons. Organization of the plant Golgi depends on actin cables and not microtubules. The common feature among Golgi is that they are adjacent to endoplasmic reticulum (ER) exit sites. In most eukaryotes, the Golgi apparatus is made up of a series of compartments and is a collection of fused, flattened membrane-enclosed disks known as cisternae (singular: cisterna , also called "dictyosomes"), originating from vesicular clusters that bud off
1462-418: The cisternae to the trans Golgi face. Enzymatic reactions within the Golgi stacks occur exclusively near its membrane surfaces, where enzymes are anchored. This feature is in contrast to the ER, which has soluble proteins and enzymes in its lumen . Much of the enzymatic processing is post-translational modification of proteins. For example, phosphorylation of oligosaccharides on lysosomal proteins occurs in
1505-632: The copper pathways and cause Wilson disease . ATP7B interacts with glutaredoxin-1 (GLRX). Subsequent transport is promoted through the reduction of intramolecular disulfide bonds by GLRX catalysis. Wilson disease happens when accumulation of copper inside the liver causes mitochondrial damage and cell destruction and shows symptoms of hepatic disease . Then, the loss of excretion of copper in bile leads to an increasing concentration of copper level in urine and causes kidney problems. Therefore, symptoms of Wilson's disease could be various including kidney disease and neurological disease . The major cause
1548-513: The early CGN. Cis cisterna are associated with the removal of mannose residues. Removal of mannose residues and addition of N-acetylglucosamine occur in medial cisternae. Addition of galactose and sialic acid occurs in the trans cisternae. Sulfation of tyrosines and carbohydrates occurs within the TGN. Other general post-translational modifications of proteins include the addition of carbohydrates ( glycosylation ) and phosphates ( phosphorylation ). Protein modifications may form
1591-434: The endoplasmic reticulum (ER). A mammalian cell typically contains 40 to 100 stacks of cisternae. Between four and eight cisternae are usually present in a stack; however, in some protists as many as sixty cisternae have been observed. This collection of cisternae is broken down into cis , medial, and trans compartments, making up two main networks: the cis Golgi network (CGN) and the trans Golgi network (TGN). The CGN
1634-410: The endoplasmic reticulum or the Golgi apparatus are moved through the Golgi cisternae towards the trans face, to a complex network of membranes and associated vesicles known as the trans-Golgi network (TGN). This area of the Golgi is the point at which proteins are sorted and shipped to their intended destinations by their placement into one of at least three different types of vesicles, depending upon
1677-420: The fundamental unanswered questions are the directionality of COPI vesicles and role of Rab GTPases in modulating protein cargo traffic. Brefeldin A (BFA) is a fungal metabolite used experimentally to disrupt the secretion pathway as a method of testing Golgi function. BFA blocks the activation of some ADP-ribosylation factors ( ARFs ). ARFs are small GTPases which regulate vesicular trafficking through
1720-405: The ionic form is known as aspartate ), is an α- amino acid that is used in the biosynthesis of proteins. The L -isomer of aspartic acid is one of the 22 proteinogenic amino acids , i.e., the building blocks of proteins . D -aspartic acid is one of two D -amino acids commonly found in mammals. Apart from a few rare exceptions, D -aspartic acid is not used for protein synthesis but
1763-508: The physiological pathway in the copper removal process in two ways: secreting copper into plasma and excreting copper into bile . ATP7B receives copper from cytosolic protein antioxidant 1 copper chaperone (ATOX1). This protein targets ATP7B directly in liver in order to transport copper. ATOX1 transfers copper from cytosol to the metal binding domain of ATP7B which control the catalytic activity of ATP7B. Several mutations in ATOX1 can block
Wilson disease protein - Misplaced Pages Continue
1806-509: The stacks together. Localization and tubular connections of the Golgi apparatus are dependent on microtubules . In experiments it is seen that as microtubules are depolymerized the Golgi apparatuses lose mutual connections and become individual stacks throughout the cytoplasm. In yeast , multiple Golgi apparatuses are scattered throughout the cytoplasm (as observed in Saccharomyces cerevisiae ). In plants , Golgi stacks are not concentrated at
1849-417: The structure as apparato reticolare interno ("internal reticular apparatus"). Some doubted the discovery at first, arguing that the appearance of the structure was merely an optical illusion created by Golgi’s observation technique. With the development of modern microscopes in the twentieth century, the discovery was confirmed. Early references to the Golgi apparatus referred to it by various names, including
#84915