RHO protein GDP dissociation inhibitor | |||||||||
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![]() Structure of RHO guanine nucleotide dissociation inhibitor. [1] | |||||||||
Identifiers | |||||||||
Symbol | Rho_GDI | ||||||||
Pfam | PF02115 | ||||||||
InterPro | IPR000406 | ||||||||
SCOP | 1rho | ||||||||
SUPERFAMILY | 1rho | ||||||||
OPM superfamily | 91 | ||||||||
OPM protein | 1qvy | ||||||||
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RHO protein GDP dissociation inhibitor of Rho proteins (rho GDI), regulates GDP/GTP exchange.
The Rho family of GTPases is a family of small signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants. Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. All G proteins are "molecular switches", and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions.
Guanosine diphosphate, abbreviated GDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of a pyrophosphate group, a pentose sugar ribose, and the nucleobase guanine.
Guanosine-5'-triphosphate (GTP) is a purine nucleoside triphosphate. It is one of the building blocks needed for the synthesis of RNA during the transcription process. Its structure is similar to that of the guanine nucleobase, the only difference being that nucleotides like GTP have a ribose sugar and three phosphates, with the nucleobase attached to the 1' and the triphosphate moiety attached to the 5' carbons of the ribose.
The protein plays an important role in the activation of the oxygen superoxide-generating NADPH oxidase of phagocytes. This process requires the interaction of membrane-associated cytochrome b559 with 3 cytosolic components: p47-phox, p67-phox and a heterodimer of the small G-protein p21Rac1 and rho GDI. [2] The association of p21rac and GDI inhibits dissociation of GDP from p21rac, thereby maintaining it in an inactive form. The proteins are attached via a lipid tail on p21rac that binds to the hydrophobic region of GDI. [3] Dissociation of these proteins might be mediated by the release of lipids (e.g., arachidonate and phosphatidate) from membranes through the action of phospholipases. [3] The lipids may then compete with the lipid tail on p21rac for the hydrophobic pocket on GDI.
A superoxide is a compound that contains the superoxide anion, which has the chemical formula O−
2. The systematic name of the anion is dioxide(1−). The reactive oxygen anion superoxide is particularly important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature. Molecular oxygen (dioxygen) is a diradical containing two unpaired electrons, and superoxide results from the addition of an electron which fills one of the two degenerate molecular orbitals, leaving a charged ionic species with a single unpaired electron and a net negative charge of −1. Both dioxygen and the superoxide anion are free radicals that exhibit paramagnetism.
NADPH oxidase is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white blood cells to engulf microorganisms. Human isoforms of the catalytic component of the complex include NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1, and DUOX2.
Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are essential for fighting infections and for subsequent immunity. Phagocytes are important throughout the animal kingdom and are highly developed within vertebrates. One litre of human blood contains about six billion phagocytes. They were discovered in 1882 by Ilya Ilyich Mechnikov while he was studying starfish larvae. Mechnikov was awarded the 1908 Nobel Prize in Physiology or Medicine for his discovery. Phagocytes occur in many species; some amoebae behave like macrophage phagocytes, which suggests that phagocytes appeared early in the evolution of life.
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.
The Rab family of proteins is a member of the Ras superfamily of small G proteins. Approximately 70 types of Rabs have now been identified in humans. Rab proteins generally possess a GTPase fold, which consists of a six-stranded beta sheet which is flanked by five alpha helixes. Rab GTPases regulate many steps of membrane trafficking, including vesicle formation, vesicle movement along actin and tubulin networks, and membrane fusion. These processes make up the route through which cell surface proteins are trafficked from the Golgi to the plasma membrane and are recycled. Surface protein recycling returns proteins to the surface whose function involves carrying another protein or substance inside the cell, such as the transferrin receptor, or serves as a means of regulating the number of a certain type of protein molecules on the surface.
Respiratory burst is the rapid release of reactive oxygen species from different types of cells.
NADPH oxidase 2 (Nox2), also known as cytochrome b(558) subunit beta or Cytochrome b-245 heavy chain, is a protein that in humans is encoded by the NOX2 gene. The protein is a super-oxide generating enzyme which forms reactive oxygen species (ROS).
Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity. Some GEFs can activate multiple GTPases while others are specific to a single GTPase.
The PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes.
Neutrophil cytosol factor 1, also known as p47phox, is a protein that in humans is encoded by the NCF1 gene.
NADPH oxidase 1 is an enzyme that in humans is encoded by the NOX1 gene.
Rab GDP dissociation inhibitor alpha is a protein that in humans is encoded by the GDI1 gene.
Rac2 is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RAC2.
Neutrophil cytosol factor 4 is a protein that in humans is encoded by the NCF4 gene.
Rho GDP-dissociation inhibitor 1 is a protein that in humans is encoded by the ARHGDIA gene.
RhoG is a small monomeric GTP-binding protein, and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small G proteins and is encoded by the gene RHOG.
Dock2, also known as DOCK2, is a large protein involved in intracellular signalling networks. It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock2 specifically activates isoforms of the small G protein Rac.
NADPH oxidase, EF-hand calcium binding domain 5, also known as NOX5, is a protein which in humans is encoded by the NOX5 gene.
NADPH oxidase organizer 1 is an enzyme that in humans is encoded by the NOXO1 gene.
Rho GDP-dissociation inhibitor 3 is a protein that in humans is encoded by the ARHGDIG gene.
NADPH oxidase 3 is an enzyme that in humans is encoded by the NOX3 gene.
NADPH oxidase activator 1 is an enzyme that in humans is encoded by the NOXA1 gene.
This article incorporates text from the public domain Pfam and InterPro IPR000406
The public domain consists of all the creative works to which no exclusive intellectual property rights apply. Those rights may have expired, been forfeited, expressly waived, or may be inapplicable.
Pfam is a database of protein families that includes their annotations and multiple sequence alignments generated using hidden Markov models. The most recent version, Pfam 32.0, was released in September 2018 and contains 17,929 families.
InterPro is a database of protein families, domains and functional sites in which identifiable features found in known proteins can be applied to new protein sequences in order to functionally characterise them.
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