The ATP Synthase allows protons to re-enter the mitochondrial matrix and harvests their energy to make ATP. ATP synthase mechanism. Figure 5.32 illustrate the multi-subunit nature of this membrane protein, which acts like a turbine at a hydroelectric dam. The movement of protons through the ATP Synthase c-ring causes it and the γ-ε stalk ...Although ATP synthase complexes have been investigated for more than 50 years, several key questions remain. An enduring question is how the stoichiometrically mismatched c ring in F o (composed of 8 to 17 c subunits) and the three-fold symmetric F 1 head are efficiently coupled. Another open question is the exact pathway taken by …The position of subunit ε shows how it is able to inhibit ATP hydrolysis while allowing ATP synthesis. The architecture of the membrane region shows how the simple …Er ist mit einem Enzym gekoppelt, das für die Synthese von energiereichem ATP aus den energiearmen Verbindungen ADP und Phosphat sorgt. Achtung die ATP-Synthase gehört nicht mehr zur Atmungskette! Aber nur sie sorgt für die Energiegewinnung in Form von ATP. Wir Menschen synthetisieren pro Tag circa 10 25 – ATP Moleküle aus ADP. Das ...The ease with which Tetrahymena can be grown, the size of the cells, the abundance of mitochondria in each cell, and availability of standardized techniques to ...ATP synthase is the ubiquitous enzyme, which is observed in various energy-transducing membranes such as thylakoid membranes in chloroplasts and cyanobacteria, inner membranes of mitochondria, and plasma membranes of prokaryotic bacteria. This enzyme synthesizes ATP from ADP and inorganic phosphate using the electrochemical proton …The mammalian mitochondrial ATP synthase (F 0 F 1) is a large protein complex ( Fig. 1A) located in the inner membrane, where it catalyzes ATP synthesis from ADP, P i, and Mg 2+ at the expense of an electrochemical gradient of protons generated by the electron transport chain (reviewed in Refs. 1. and. 2.Boyer and Walker received the Nobel Prize in 1997 for elucidating the mechanism of ATP synthase. This is all-important reactions in which the proton-motive force, produced by proton translocation, is coupled to the synthesis of ATP from ADP and phosphate. ATP synthase is a complex structure consisting of two domains F O and F 1.Jan 21, 2013 · The Intelligent Design of Molecular Machines in the Cell:ATP Synthase is a molecular machine found in many living organisms. It serves as a miniature power-g... Molecular animations of ATP synthase. A series of animations that we have made to illustrate the function and assembly of the mitochondrial ATP synthase. F₁-ATPase catalytic site binding and hydrolysis of ATP. Above and then …The ATP synthase enzyme catalyses the production of ATP from ADP and inorganic phosphate. It does so using a clever internal rotary mechanism, the latest insight into which is now reported. Using ...The flow of protons through the membrane turbines rotates the stalk of the ATP synthase, and the conformational changes induced by this rotation catalyze ATP synthesis.ATP synthase is located in the inner membrane of mitochondria. ATP synthesis occurs alongside photosynthesis during the light stage reaction. ATP synthesis takes place by proton gradient produced across the thylakoid membrane. An example of ATP synthase that occurs in mitochondria, chloroplast, and bacterial plasma membrane is F-ATPase.Chloroplast ATP synthase (CF 1 F O) from higher plants has a unique redox switch that serves to modulate the ATP synthesis activity 4, 6, 7. The CF 1 F O enzyme actively synthesizes ATP in the ...ATP-Synthase. Die ATP-Synthase ist ein komplexes Transmembranprotein, das die über den elektrochemischen Gradienten gespeicherte potenzielle Energie zur ...Figure 1 The ATP synthase. The enzyme fromE. coli has an F 1 portion with subunits designated as α 3 β 3 γδε. When separated it acts as an ATPase. The F 0 portion subunits are designated as ab 2 c 9–12.The passage of protons, at the interface of the a subunit and the ring of c subunits, causes a rotation of the c and attached ε and γ subunits relative to …Jan 1, 2011 · Abstract. ATP production in the thylakoid membranes of chloroplasts and cyanobacteria as well as in the inner membranes of mitochondria and bacterial plasma membranes is catalyzed by ATP synthase, a complex, evolutionary conserved multi-subunit enzyme. Whereas ATP synthase was discovered already more than 40 years ago, the last 10–15 years ... ATP synthase has two major structural parts known as F 1 and F o linked by the peripheral and central stalks. The F 1 catalytic domain of the mitochondrial enzyme is a globular assembly of five different proteins, α, β, γ, δ and ε with the stoichiometry 3:3:1:1:1 [1]. The three α-subunits and the three β-subunits are arranged alternately ...Molecular animations of ATP synthase. A series of animations that we have made to illustrate the function and assembly of the mitochondrial ATP synthase. F₁-ATPase catalytic site binding and hydrolysis of ATP. Above and then …A complete structure of the human ATP synthase complex. ADP release occurs when the subunit is in the open conformation. Water molecules are defined in the inlet and outlet proton half-channels. Clinically relevant mutations cause the instability of the complex. Lai et al., 2023, Molecular Cell , 2137–2147. 83 June 15, 2023 2023 Elsevier Inc.May 26, 2023 · Introduction. ATP synthase (also known as the F 1 F o -ATPase or complex V) embedded in the inner mitochondrial membrane (IMM) provides the bulk of cellular ATP, the universal source of energy currency. 1. This enzyme catalyzes the last step of oxidative phosphorylation (OXPHOS) under aerobic respiration. 2. Dec 31, 2020 · ATP synthase is a huge molecular complex (>500,000 daltons) embedded in the inner membrane of mitochondria. Its function is to convert the energy of protons (H +) moving down their concentration gradient into the synthesis of ATP. 3 to 4 protons moving through this machine is enough to convert a molecule of ADP and P i (inorganic phosphate ... In this animation, Professor Rob Lue describes the action of the ATP synthase.From our free online course, “Cell Biology: Mitochondria”: https://www.edx.org/... NADH, a molecule produced during cellular respiration, gets oxidized and releases electrons. These electrons pass through a series of acceptors in the electron transport chain, releasing energy. This energy pumps hydrogen protons across a membrane, creating a gradient. Finally, the enzyme ATP synthase uses this gradient to produce ATP.F1FO ATP synthase molecular motor mechanisms ... The F-ATP synthase, consisting of F 1 and F O motors connected by a central rotor and the stators, is the enzyme ...a ATP synthase (left) consists of an F 1 and an F O region with a shared rotor subcomplex (outlined in black) and a peripheral stalk (green). Rotation driven by proton translocation through the F ...NADH, a molecule produced during cellular respiration, gets oxidized and releases electrons. These electrons pass through a series of acceptors in the electron transport chain, releasing energy. This energy pumps hydrogen protons across a membrane, creating a gradient. Finally, the enzyme ATP synthase uses this gradient to produce ATP.The architecture and subunit composition of ATP synthase. ATP synthase is a large mushroom-shaped asymmetric protein complex. The simplest bacterial enzyme (see the cartoon below) is composed of 8 subunit types, of which 5 form the catalytic hydrophilic F 1-portion (the "cap" of the mushroom).These subunits are named by Greek letters …The proton channel is a part of the ATP synthase enzyme. As a proton passes through this channel, it liberates energy. This energy is used to phosphorylate ADP to form ATP. Z-Reaction. It is the other name of light reactions of photosynthesis. In this reaction, the energy for phosphorylation is provided by sunlight.三磷酸腺苷合酶或ATP合酶，三磷酸腺苷酶（ATPase）的一种，在这里并特指F类的F o F 1 ATP合酶（F Type F o F 1 ATP Synthase）。它利用呼吸链产生的质子的电化学势能，通过改变蛋白质的结构来进行三磷酸腺苷(ATP)的合成。ATP是大多数生物体中细胞最常用的“能量通货”。 Oct 2, 2020 · ATP Synthesis | This animation shows how the proton gradient across the mitochondrial membrane powers the ATP synthase enzyme to make ATP. It is the fifth of six animations about cellular respiration. These animations bring to life the molecular engines inside mitochondria that generate ATP, the main source of chemically stored energy used ... Apr 12, 2012 · ATP management within the cell. Schematic representation of mechanisms of ATP synthesis and storage inside the cell. Glycolysis is represented in the yellow and blue boxes, the TCA cycle by the green circle, and oxidative phosphorylation in the orange box. Reduction of pyruvate to lactate is represented inside the red dotted rectangle. The structure of ATP synthase determined at pH 8 (Protein Data Bank (PDB) 6CP6) 2 fits well in the Conf-0 maps, and both align well with the cryo-EM map of bovine ATP synthase in state 2 (Extended ...Mar 7, 2023 · The mitochondrial ATP synthase, an enzyme that synthesizes ATP and is involved in the formation of the mitochondrial mega-channel and permeability transition, is a multi-subunit complex. In S ... Distribution of ATP synthases across Bacteria, Archaea and Eukaryotes. We analysed the distribution of ATP synthase genes across our reference genome dataset of 800 Archaea, Bacteria, and eukaryotes (Figs. 1 – 2, Supplementary Fig. 2, Supplementary Data 1 – 4).In agreement with previous work 29, 32 – 36, 38, 40, our results indicate a …31 Jul 2023 ... A channel in ATP synthase allows protons to diffuse back across the membrane, releasing energy that triggers the enzyme catalysing ATP ...Aug 3, 2021 · F 1 F o ATP synthase is a biological rotary motor that utilizes a rotary catalytic mechanism to couple proton translocation across a membrane with the synthesis of adenosine triphosphate (ATP ... ATP synthase is an enzyme that produces ATP, the main energy molecule used by cells. It has two parts: F O, a motor powered by H+ ions, and F 1 -ATPase, a motor that converts ADP and P i into ATP. …3 Oct 2018 ... Similar to the rates of ATP synthesis, ATP hydrolysis measurements indicate that ATP synthase activity is strongly inhibited by temperature.6 Apr 2023 ... Abstract ... The mitochondrial F1Fo‐ATP synthase (also called complex V) is a remarkable enzyme and is fundamental for eukaryotic life. The enzyme ...Figure 2: The electrochemical proton gradient and ATP synthase At the inner mitochondrial membrane, a high energy electron is passed along an electron transport chain. The energy released pumps ...Introduction. F O F 1 ATP synthase, a ubiquitous enzyme that synthesizes most ATP in living cells, comprises two rotary motors: the membrane-embedded proton-driven F O motor and the catalytic F 1 motor; these motors share the central rotor and peripheral stalk. The F O motor harbors a ring-shaped c-subunit oligomer, which serves …Nov 17, 2023 · The ATP synthase is a protein complex central to energy conservation through the synthesis and hydrolysis of ATP 29, 30. It is a useful marker to address key evolutionary transitions due to the ... ATP synthase is a ubiquitous, highly conserved enzyme that catalyses the formation of ATP from ADP and P i using a unique rotary …ATP Synthase Structure. ATP synthase is composed of two parts, F 0 and F 1, which are situated within the inner mitochondrial membrane and the thylakoid membrane (CF 0 and CF 1).. F 0 is the portion that is embedded inside the mitochondrial membrane (in eukaryotes), thylakoid membrane (in plants), or plasma membrane (in prokaryotes). F 0 …A complete structure of the human ATP synthase complex. ADP release occurs when the subunit is in the open conformation. Water molecules are defined in the inlet and outlet proton half-channels. Clinically relevant mutations cause the instability of the complex. Lai et al., 2023, Molecular Cell , 2137–2147. 83 June 15, 2023 2023 Elsevier Inc.The mitochondrial ATP synthase, an enzyme that synthesizes ATP and is involved in the formation of the mitochondrial mega-channel and permeability transition, is a multi-subunit complex. In S ...May 7, 2017 · An amazing molecular machine, ATP synthase, can run use electrostatic potential energy stored in a proton gradient to generate ATP. Under different condition... May 5, 2018 · The chloroplast ATP synthase uses the electrochemical proton gradient generated by photosynthesis to produce ATP, the energy currency of all cells. Protons conducted through the membrane-embedded F o motor drive ATP synthesis in the F 1 head by rotary catalysis. We determined the high-resolution structure of the complete cF 1 F o complex by ... This represents a proton-motive force of about 200 mV across the thylakoid membrane, and it drives ATP synthesis by the ATP synthase embedded in this membrane. The force is the same as that across the inner …Sep 1, 2001 · ATP synthase is a ubiquitous, highly conserved enzyme that catalyses the formation of ATP from ADP and P i using a unique rotary motor mechanism. The enzyme is located in the inner membrane of... Mar 6, 2022 · ATP synthases of F-type (F O F 1) are found embedded in bacterial cellular membrane, in thylakoid membranes of chloroplasts, and in mitochondrial inner membranes in eukaryotes. The main functions of ATP synthases are control of the ATP synthesis and transmembrane potential. Although the key subunits of the enzyme remain highly conserved ... PubMed Abstract: Biological energy currency ATP is produced by F 1 F o -ATP synthase. However, the molecular mechanism for human ATP synthase action remains unknown. Here, we present snapshot images for three main rotational states and one substate of human ATP synthase using cryoelectron microscopy. These structures …ATP synthase as a complex of two motors — an ATP-driven F 1 motor and a proton-driven F o motor. They are connected by a common rotary shaft and their genuine directions of rotation are opposite ...Figure 2: The electrochemical proton gradient and ATP synthase At the inner mitochondrial membrane, a high energy electron is passed along an electron transport chain. The energy released pumps ...A short video describing F1Fo ATP synthase function.We made this a couple of years ago for the late Richard Perham to explain ATP synthase function for the b...An amazing molecular machine, ATP synthase, can run use electrostatic potential energy stored in a proton gradient to generate ATP. Under different condition...The permeability transition in human mitochondria refers to the opening of a non-specific channel, known as the permeability transition pore (PTP) in the inner membrane. Opening can be triggered by calcium ions, leading to swelling of the organelle, disruption of the inner membrane and ATP synthesis, followed by cell death [1] [2].Jan 29, 1998 · Abstract. Mitochondria, bacteria and chloroplasts use the free energy stored in transmembrane ion gradients to manufacture ATP by the action of ATP synthase. This enzyme consists of two principal ... 13 Aug 2002 ... The ATPase was known to have two or three copies of major α and β subunits and single copies of other smaller subunits. The unusual subunit ...The energy released by the hydrogen ion stream allows ATP synthase to attach a third phosphate group to ADP, which forms a molecule of ATP (Figure \(\PageIndex{8}\)). The flow of hydrogen ions through ATP synthase is called chemiosmosis because the ions move from an area of high to an area of low concentration through a semi-permeable …Die ATP-Synthase hat ein anderes „Übersetzungsverhältnis“ als die Protonenpumpen-ATPasen. Letztere pumpen pro verbrauchtem ATP ca. zwei Protonen nach außen. Bei ...This represents a proton-motive force of about 200 mV across the thylakoid membrane, and it drives ATP synthesis by the ATP synthase embedded in this membrane. The force is the same as that across the inner …ATP synthase is the ubiquitous enzyme, which is observed in various energy-transducing membranes such as thylakoid membranes in chloroplasts and cyanobacteria, inner membranes of mitochondria, and plasma membranes of prokaryotic bacteria. This enzyme synthesizes ATP from ADP and inorganic phosphate using the electrochemical proton …PubMed Abstract: Biological energy currency ATP is produced by F 1 F o -ATP synthase. However, the molecular mechanism for human ATP synthase action remains unknown. Here, we present snapshot images for three main rotational states and one substate of human ATP synthase using cryoelectron microscopy. These structures …Introduction. F O F 1 ATP synthase, a ubiquitous enzyme that synthesizes most ATP in living cells, comprises two rotary motors: the membrane-embedded proton-driven F O motor and the catalytic F 1 motor; these motors share the central rotor and peripheral stalk. The F O motor harbors a ring-shaped c-subunit oligomer, which serves …The ALAS2 gene provides instructions for making an enzyme called 5'-aminolevulinate synthase 2 or erythroid ALA-synthase. Learn about this gene and related health conditions. The A...A key component in the generation of cellular metabolic energy is the F 1 F o ATP synthase, a biological rotary motor that converts the proton motive force (pmf) to adenosine tri-phosphate (ATP ...(1R,2S)-1-(6-Bromo-2-methoxyquinolin · (1R,2S)-1-(6-Bromo-2-methoxyquinolin · (1R,2S)-1-(6-Bromo-2-methoxyquinolin.Key Terms. synthase: Any enzyme that catalyzes the synthesis of a biological compound but, unlike synthetases, does not make use of ATP as a source of energy; adenosine triphosphate: Adenosine-5′-triphosphate (ATP) is a multifunctional nucleoside triphosphate used in cells as a coenzyme.It is often called the “molecular unit …ATP synthase - an overview. The final step in oxidative phosphorylation and photophosphorylation, the synthesis of ATP from ADP and inorganic phosphate, is catalyzed by F 1 F o-ATP synthase. The driving force for ATP synthesis is a transmembrane proton (or, in some organisms, sodium ion) gradient. Abstract. Mitochondria, bacteria and chloroplasts use the free energy stored in transmembrane ion gradients to manufacture ATP by the action of ATP synthase. This enzyme consists of two principal ...The structure of ATP synthase determined at pH 8 (Protein Data Bank (PDB) 6CP6) 2 fits well in the Conf-0 maps, and both align well with the cryo-EM map of bovine ATP synthase in state 2 (Extended ...This biology video tutorial provides a basic introduction into the electron transport chain - a series of membrane bound proteins that shuttle the electrons ...The mammalian mitochondrial ATP synthase (F 0 F 1) is a large protein complex ( Fig. 1A) located in the inner membrane, where it catalyzes ATP synthesis from ADP, P i, and Mg 2+ at the expense of an electrochemical gradient of protons generated by the electron transport chain (reviewed in Refs. 1. and. 2.This gradient between stroma and lumen can be maintained because the thylakoid membrane is generally impermeable to protons. The energy inherent in the proton ...Medicine Matters Sharing successes, challenges and daily happenings in the Department of Medicine ARTICLE: Myocardial ATP depletion detected noninvasively predicts sudden cardiac d...The protons flow back into the matrix through an enzyme called ATP synthase, making ATP. At the end of the electron transport chain, oxygen accepts electrons and takes up protons to form water. During cellular respiration, a glucose molecule is gradually broken down into carbon dioxide and water. Along the way, some ATP is produced directly in ...The F-ATP synthase, consisting of F1 and FO motors connected by a central rotor and the stators, is the enzyme responsible for synthesizing the majority of ATP ...ATP Synthase Structure. ATP synthase is composed of two parts, F 0 and F 1, which are situated within the inner mitochondrial membrane and the thylakoid membrane (CF 0 and CF 1).. F 0 is the portion that is embedded inside the mitochondrial membrane (in eukaryotes), thylakoid membrane (in plants), or plasma membrane (in prokaryotes). F 0 …14 Apr 2016 ... A short video describing F1Fo ATP synthase function. We made this a couple of years ago for the late Richard Perham to explain ATP synthase ...別名atpシンターゼ、呼吸鎖複合体v、複合体vなど。 なお、シンテターゼはatpなどの高エネルギー化合物の分解と共役する反応を触媒する酵素を指すが、atp合成に他のエネルギー化合物を用いることはないので、「atpシンテターゼ」という呼称は正しくない。 ATP synthase dimers and dimer rows are thus a prerequisite for proper cristae formation. Although the loss of the dimer-specific subunits is not lethal, it is a serious disadvantage. Yeast subunit e and g knockout strains grow up to 60 % more slowly than wild type and their mitochondria only have about half the membrane potential . This raises ...ATP synthase is the central enzyme in energy conversion in mitochondria (where they are embedded into the cristae, folds in the mitochondrion’s inner membrane), chloroplasts and bacteria. This probably makes ATP synthase the most ubiquitous protein on Earth. Since energy is required for life, and all life uses ATP as its energy currency (each ...Figure 1 The ATP synthase. The enzyme fromE. coli has an F 1 portion with subunits designated as α 3 β 3 γδε. When separated it acts as an ATPase. The F 0 portion subunits are designated as ab 2 c 9–12.The passage of protons, at the interface of the a subunit and the ring of c subunits, causes a rotation of the c and attached ε and γ subunits relative to …ATP synthase is thought of as having three states. In the "loose" state, ADP and phosphate (Pi) can enter the binding site easily. Once these two substrates are in the binding site, the enzyme enters the "tight" state, in which ADP and phosphate are constricted and form ATP. At that point, the enzyme goes through an "open" phase in which ATP ...The chloroplast adenosine triphosphate (ATP) synthase uses the electrochemical proton gradient generated by photosynthesis to produce ATP, the energy currency of all cells. Protons conducted through the membrane-embedded F o motor drive ATP synthesis in the F 1 head by rotary catalysis. We determined the high-resolution …ATP synthase is located in the inner membrane of mitochondria. ATP synthesis occurs alongside photosynthesis during the light stage reaction. ATP synthesis takes place by proton gradient produced across the thylakoid membrane. An example of ATP synthase that occurs in mitochondria, chloroplast, and bacterial plasma membrane is F-ATPase.ATP synthase is the ubiquitous enzyme, which is observed in various energy-transducing membranes such as thylakoid membranes in chloroplasts and cyanobacteria, inner membranes of mitochondria, and plasma membranes of prokaryotic bacteria. This enzyme synthesizes ATP from ADP and inorganic phosphate using the electrochemical proton …
A complete structure of the human ATP synthase complex. ADP release occurs when the subunit is in the open conformation. Water molecules are defined in the inlet and outlet proton half-channels. Clinically relevant mutations cause the instability of the complex. Lai et al., 2023, Molecular Cell , 2137–2147. 83 June 15, 2023 2023 Elsevier Inc.. Mariah carey hero
As the protons move down the concentration gradient through the ATP synthase, the energy released causes the rotor and rod of the ATP synthase to rotate. The ...An amazing molecular machine, ATP synthase, can run use electrostatic potential energy stored in a proton gradient to generate ATP. Under different condition...A short video describing F1Fo ATP synthase function.We made this a couple of years ago for the late Richard Perham to explain ATP synthase function for the b...ATP Synthase is a complex structure consisting of two domains F o and F 1. F 1 is a spherical structure, which, in the case of mitochondria, sticks out into the matrix and is anchored to the membrane by a stator to prevent rotation. It consists of three α- and three β- subunits, all of which can bind nucleotides, but only the β-subunits can ...ATP synthase is a protein complex that uses protons across a membrane to drive the synthesis of ATP from ADP and phosphate. It is found in mitochondria and …Aug 27, 2011 · A recent yeast study indicated that ATP synthase is formed from three different modules: the c-ring, F 1 and the Atp6p/Atp8p complex (Rak et al. 2011). It is proposed that ATP synthase assembly in yeast involves two separate pathways (F 1 /Atp9p and Atp6p/Atp8p/2 stator subunits/Atp10p chaperone) that converge at the end stage (Rak et al. 2011). Nov 17, 2023 · The ATP synthase is a protein complex central to energy conservation through the synthesis and hydrolysis of ATP 29, 30. It is a useful marker to address key evolutionary transitions due to the ... The F-type, A-type, and V-type family of rotary molecular motors. The F 1 F O ATP synthase (), which is found in all animals, plants, and eubacteria, provides the largest source of ATP that fuels most cellular processes (Spetzler et al., 2012; Kühlbrandt, 2019).The F 1 F o complexes use a non-equilibrium proton gradient (or Na + gradient in …ATP synthase is a protein complex that produces ATP from ADP using the energy of protons from the electron transport chain. Learn about its structure, …Mar 13, 2023 · The maintenance of cellular function relies on the close regulation of adenosine triphosphate (ATP) synthesis and hydrolysis. ATP hydrolysis by mitochondrial ATP Synthase (CV) is induced by loss of proton motive force and inhibited by the mitochondrial protein ATPase inhibitor (ATPIF1). NDSU Virtual Cell Animations Project animation 'Gradients (ATP Synthase)'. For more information please see http://vcell.ndsu.edu/animationsGradients are used...ATP Synthase in Photosynthesis ... ATP synthase is a transmembrane enzyme complex, which catalyses the generation of ATP through the condensation of ADP plus Pi.The upper part of the ATP synthase complex rotates when a new hydrogen ion enters. Once three protons have entered the matrix space, there is enough energy in the ATP synthase complex to synthesize one ATP. In this way, the energy in the hydrogen ion gradient is used to make ATP. Now let’s watch the process again… The ATP synthase of mitochondria and chloroplasts is an anabolic enzyme that harnesses the energy of a transmembrane proton gradient as an energy source for adding an inorganic phosphate group to a molecule of adenosine diphosphate (ADP) to form a molecule of adenosine triphosphate (ATP). Furthermore, synuclein deficiency results in reduced ATP synthase efficiency and lower ATP levels. Exogenous application of low unfolded α-synuclein concentrations is able to increase the ATP synthase activity that rescues the mitochondrial phenotypes observed in synuclein deficiency. Overall, the data suggest that α-synuclein is a ….