• Background: Rab proteins are GTPases responsible for intracellular vesicular trafficking regulation. (researchsquare.com)
  • These findings highlight plasticity in the activation mechanisms of closely related Rab GTPases. (elifesciences.org)
  • Widespread domain present in Gyp6 and Gyp7, thereby giving rise to the notion that it performs a GTP-activator activity on Rab-like GTPases. (embl.de)
  • Ras proteins are small GTPases (20-25kDa) that comprise a larger superfamily of proteins divided into five subfamilies: Ras, Rho, Rab, Arf, and Ran. (promegaconnections.com)
  • GTPases are guanosine-nucleotide-binding proteins with affinity for GDP or GTP and are able to hydrolyze GTP. (promegaconnections.com)
  • When bound to GTP, GTPases are active (turned on) and interact with downstream proteins in the signaling cascade. (promegaconnections.com)
  • When GTPases are bound to GDP, the proteins are inactivated (turned off) and no longer transduce signals. (promegaconnections.com)
  • Small G-proteins, monomeric GTPases, or the RAS (Rat sarcoma) superfamily are a large family of small guanine nucleotide-binding proteins with molecular weights ranging from 20 to 30 kDa [ 1 , 2 ]. (oncotarget.com)
  • We provide evidence that KRas translocation occurs through sequestration of the polybasic-prenyl motif by Ca 2+ /calmodulin (Ca 2+ /CaM) and subsequent release of KRas from the PM, in a process reminiscent of GDP dissociation inhibitor-mediated membrane recycling of Rab and Rho GTPases. (rupress.org)
  • Ras proteins are the founding members of the Ras superfamily of GTPases, which in humans is composed of more than 150 members [ 1 ] [ 2 ] . (encyclopedia.pub)
  • Ras proteins are membrane-bound small GTPases that act as molecular transducers, coupling cell surface receptors to intracellular effector pathways to regulate cellular processes such as cell proliferation, differentiation, migration, and apoptosis [ 3 ] [ 4 ] . (encyclopedia.pub)
  • We focus on the Rab GTPases that are master regulators of membrane trafficking. (stanford.edu)
  • Activating mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) cause Parkinson's disease and previously we showed that activated LRRK2 phosphorylates a subset of Rab GTPases (Steger et al. (stanford.edu)
  • Rab11 proteins, members of the Rab GTPase family, are known to regulate vesicular recycling during embryonic development. (researchsquare.com)
  • The zebrafish Rab11a, Rab11ba and Rab11bb proteins are highly conserved during evolution, especially the GTPase domain, suggesting their important functions. (researchsquare.com)
  • Ras superfamily GTPase activation and inactivation occur by canonical nucleotide exchange and GTP hydrolysis mechanisms. (elifesciences.org)
  • Despite conservation of active-site residues, the Ras-related Rab GTPase activation pathway differs from Ras and between different Rabs. (elifesciences.org)
  • The ~200 amino acid TBC/rab GTPase-activating protein (GAP) domain is well conserved across species and has been found in a wide range of different proteins from plant adhesion molecules to mammalian oncogenes. (embl.de)
  • It has been proposed that this cleft is the binding site for the GTPase. (embl.de)
  • Identification of a Sec4p GTPase-activating protein (GAP) as a novel member of a Rab GAP family. (embl.de)
  • A yeast open reading frame sharing homology with the two known yeast Rab GTPase-activating proteins (GAPs), Gyp6p and Gyp7p, was found in a data base search. (embl.de)
  • Gyp1p also stimulated the GTPase activity of several other yeast Rab proteins including Ypt1p, Ypt7p, and Ypt51p but showed no GAP activity on Ypt6p and Ypt32p. (embl.de)
  • Belongs to the small GTPase superfamily. (lu.se)
  • Ras is a small GTPase that operates as a binary molecular switch between a GDP-bound inactive and GTP-bound active state. (rupress.org)
  • Similar to other small G proteins, the guanine binding state of Rab3 proteins is regulated by guanine nucleotide exchange proteins or factors (GEPs or GEFs) and GTPase activating proteins (GAPs). (pancreapedia.org)
  • Patrick A. Lewis ABSTRACT Leucine-rich repeat kinase 2 (LRRK2) is a multidomain scaffolding protein with dual guanosine triphosphatase ( GTPase ) and kinase enzymatic activities, providing this protein with the capacity to regulate a multitude of signalling pathways. (biologists.com)
  • engagement triggers rapid GTP-loading of the small GTPase Rac as a master regulator of cytoskeletal rearrangements and lamellipodia-driven internalization. (biologists.com)
  • Macropinocytosis GTPase Rab Phosphatase Phosphoinositide EGF Ruffling Macropinocytosis is an actin-driven process that involves the formation and extension of plasma membrane ruffles and the eventual closure of large (≥0.2 to 5.0. (biologists.com)
  • ARHGAP21 interacts with RhoA-GTP, and acts as a GAP to increase RhoA GTPase activity. (uth.edu)
  • Rho GTPase activating protein 6 [So. (gsea-msigdb.org)
  • GDP dissociation inhibitors are proteins that regulate the GDP-GTP exchange reaction of members of the rab family, small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles. (wikipedia.org)
  • The 70 or so members of the Rab subfamily of proteins perform a wide range of important tasks inside cells. (elifesciences.org)
  • Members of the Rab protein family are nontransforming monomeric GTP-binding proteins of theRas superfamily that contain 4 highly conserved regions involved in GTP binding and hydrolysis.Rabs are prenylated, membrane-bound proteins involved in vesicular fusion and trafficking. (technuc.com)
  • The second Rab3 GEF, known as GRAB, interacts with inositol hexakisphosphate kinase and Rab3A and its protein expression is primarily in brain (41). (pancreapedia.org)
  • Physiologically, the N-terminal domain of p126 binds the Src-homology 3 (SH3) domain of c-Abl, leading to activation of the MAPK/ERK2 kinase. (molcells.org)
  • The finding that yeast Rab GAPs share homology with proteins in other species, such as Caenorhabditis elegans and human, suggests the existence of a conserved Rab GAP family. (embl.de)
  • Because of its localization and homology to the yeast protein Sec4, it was believed to play a role in the terminal steps of secretion. (pancreapedia.org)
  • The p53 interacting partner protein NUMB (homology of numb protein) preserves this intrinsic cellular asymmetry by preventing ubiquitin-mediated proteolysis of p53 catalyzed by the MDM2 E3 ubiquitin ligase 11 . (nature.com)
  • Among various Rab proteins, Rab11 is known to localize to recycling endosome and regulate vesicular recycling and primary ciliogenesis, playing a key role in Kupffer vesicle development in zebrafish [5-7]. (researchsquare.com)
  • The superfamily is classified into five subfamilies based on the cellular processes that they regulate [ 2 ]. (oncotarget.com)
  • Although it did not regulate Rab 2, Rab 5, Rab 10 or Rab 11, a recent study indicates it can act on Rab 27A and 27B (23). (pancreapedia.org)
  • The combination of growth factors and RTKs can activate the PI3K/AKT signaling pathway and negatively regulate TSC1/2, promoting Rheb to become GTP loaded, which can activate mTORC1. (biomedcentral.com)
  • Rab40c is a SOCS box-containing protein which binds Cullin5 to form a ubiquitin E3 ligase complex (Rab40c/CRL5) to regulate protein ubiquitylation. (life-science-alliance.org)
  • The Rab subfamily of proteins is part of the large Ras superfamily, and all members of this superfamily are activated and inactivated in a similar way, with the binding and unbinding of GDP and GTP taking place at a structure called the G-domain. (elifesciences.org)
  • ATP binding cassette subfamily A me. (gsea-msigdb.org)
  • RAB11 was first found from cultured MDCK cell cDNA library screening for homologous genes of yeast YPT1/SEC4[3], and later identified as the 11th member of the Rab family[4]. (researchsquare.com)
  • Because Ras proteins are involved in transducing signals from the surface of cells, many of the resulting mutations produce an activated Ras, inducing uncontrolled expression of the genes that Ras controls. (promegaconnections.com)
  • In humans, three Ras genes ( H-ras , N-ras, and K-ras ) encode four distinct Ras proteins: H-Ras, N-Ras, K-Ras4A, and K-RasS4B, the latter 2 resulting from alternative RNA splicing of the K-ras gen. (encyclopedia.pub)
  • Additionally, Ras proteins are recognized as major oncogenes, as mutations in all three Ras genes occur in approximately 30% of human cancers [ 10 ] . (encyclopedia.pub)
  • The genes encoding CaaX protein prenyltransferases are considerably longer than those encoding non-CaaX subunits, as a result of longer introns. (biomedcentral.com)
  • The genomic organization of the human genes that encode protein prenyltransferases is shown in Figure 1 . (biomedcentral.com)
  • Gene structures and chromosomal locations of human protein prenyltransferase subunit genes. (biomedcentral.com)
  • (b) genes encoding non-CaaX protein prenyltransferases are much shorter. (biomedcentral.com)
  • Automatic comparisons of data from expressed sequence tags (ESTs) with genes (for example using the program Acembly, for which the results are available from the NCBI AceView server [ 2 ]) shows that all the human protein prenyltransferase genes have multiple alternative splice variants. (biomedcentral.com)
  • The chromosomal locations and number of exons from protein prenyltransferase genes in the major eukaryotic model organisms are shown in Table 2 . (biomedcentral.com)
  • So CCDS's gene number prediction represents a lower bound on the total number of human protein-coding genes. (wikidoc.org)
  • Genetic studies have clarified that most microcephaly genes encode ubiquitous proteins involved in mitosis and in maintenance of genomic stability, but the effects of their inactivation are particularly strong in neural progenitors. (cancerindex.org)
  • Starch binding domain-containing protein 1 (Stbd1) is a carbohydrate-binding protein that has been proposed to be a selective autophagy receptor for glycogen. (imperial.ac.uk)
  • Ras signaling is activated by cellular receptors including receptor tyrosine kinases (RTKs), G-protein coupled receptors (GPCRs), cytokines receptors, and extracellular matrix receptors [ 12 ] . (encyclopedia.pub)
  • G protein-coupled receptor 85 [Sour. (gsea-msigdb.org)
  • Other proteins-known as GAPs-lead to the inactivation of the Rab protein. (elifesciences.org)
  • Probable Rab-GAPs. (embl.de)
  • This study tested this hypothesis by determining the effect of the PCAIs on the levels of RAS and related monomeric G-proteins. (oncotarget.com)
  • These findings implicate the potential role of PCAIs as anticancer agents through their direct interaction with monomeric G-proteins. (oncotarget.com)
  • The structure of the Rabs changes upon binding GTP and mutant Rab3 species have been described similar to Ras that are locked into active and inactive configurations (6). (pancreapedia.org)
  • download of been proteins appears the architectural subunit of including acids within enzymes and represents the inhibitor gene conjugation SSA to intracellular families that initiate dramatically synaptic from those short at the thyroid beta. (erik-mill.de)
  • Although Rab11a subcellular localization has been demonstrated by transgenic zebrafish [10], and molecular function of Rab11 proteins in primary cilia membrane assembly in Kupffer Vesicle has been studied [6], the developmental expression profile of Rab11 proteins in zebrafish remains elusive. (researchsquare.com)
  • Together these proteins form a molecular switch that can be turned on and off. (elifesciences.org)
  • Ras proteins act as molecular switches that cycle between two conformational states: an active GTP-bound state and an inactive GDP-bound state. (encyclopedia.pub)
  • The long term goal of our research is to elucidate the molecular mechanisms by which proteins are targeted to specific and distinct compartments. (stanford.edu)
  • GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs. (wikipedia.org)
  • There is no known specific Rab3 GDI, but rather a common family of Rab GDI isoforms which bind prenylated Rabs in the cytoplasm and participates in insertion and removal from membranes (75). (pancreapedia.org)
  • The putative effector-binding site of this protein is similar to that of the RAB/YPT proteins. (nih.gov)
  • The RAS-related proteins of the RAB/YPT family may play a role in the transport of proteins from the endoplasmic reticulum to the Golgi and the plasma membrane. (nih.gov)
  • When it comes to a drug target for cancer, the Ras protein family is at the top of the list because the proteins are expressed ubiquitiously and found mutated in many types of cancer. (promegaconnections.com)
  • RAB family. (lu.se)
  • Rab proteins constitute the largest family of Ras-related small G proteins and play a role in regulating the specificity of membrane trafficking (63, 78). (pancreapedia.org)
  • Zebrafish rab11a was clustered in the Rab11a group, and rab11ba and rab11bb in the Rab11b group (Fig.1B) in the phylogenic tree constructed according to amino acid sequences of all the Rab11 proteins above. (researchsquare.com)
  • For example, the amino acid glutamine is involved when the Listeria GEF and one of the human GEFs activate the protein, whereas a different amino acid-aspartate-is involved when one of the other human GEFs is responsible for the activation. (elifesciences.org)
  • Rab GDP dissociation inhibitor beta is a protein that in humans is encoded by the GDI2 gene. (wikipedia.org)
  • Different mutations of EDA gene and EDAR gene could make different influence on the protein function and lead to the occurrence of HED. (bvsalud.org)
  • The protein encoded by this gene is a member of the RAS superfamily which are small GTP/GDP-binding proteins with an average size of 200 amino acids. (nih.gov)
  • This gene encodes a large protein that functions as a GDP to GTP exchange factor. (cancerindex.org)
  • What does this gene/protein do? (cancerindex.org)
  • What pathways are this gene/protein implicaed in? (cancerindex.org)
  • Pathological Tau transmission initiated by binding lymphocyte-activation gene 3. (neurotree.org)
  • The contractile ring is made up of structural proteins, including actin filaments and myosin II filaments. (jove.com)
  • A protein called RhoA is the chief regulator of contractile ring assembly and function. (jove.com)
  • Themammalian RAB proteins show striking similarities to the S. cerevisiae YPT1 and SEC4 proteins,Ras-related GTP-binding proteins involved in the regulation of secretion. (technuc.com)
  • This protein shares 97%, 96%, and 51% similarity with the dog RAB8, mouse MEL, and mouse YPT1 proteins, respectively and contains the 4 GTP/GDP-binding sites that are present in all the RAS proteins. (nih.gov)
  • However, this protein contains a C-terminal CAAX motif that is characteristic of many RAS superfamily members but which is not found in YPT1 and the majority of RAB proteins. (nih.gov)
  • We discuss how recent chemical proteomic approaches have delivered the first global overviews of protein lipidation in these organisms, contributing to our understanding of the role of this PTM in critical metabolic and cellular functions. (imperial.ac.uk)
  • The cytoskeleton is a highly dynamic network of filamentous proteins that enables the active transport of cellular cargo, transduces force, and when assembled into higher-order structures, forms the basis for motile cellular structures that promote cell movement. (mechanobio.info)
  • Ras proteins are essential mediators of a multitude of cellular processes, and its deregulation is frequently associated with cancer appearance, progression, and metastasis. (encyclopedia.pub)
  • Enhanced mTORC1 signaling and protein synthesis in pathologic α-synuclein cellular and animal models of Parkinson's disease. (neurotree.org)
  • The α subunits of protein prenyltransferases consist of tetratricopeptide repeats and are part of the tetratricopeptide repeat superfamily [ 5 ], which also includes functionally diverse proteins involved in transcription, co-chaperoning, protein transport, cell-cycle control and phosphorylation. (biomedcentral.com)
  • Conserved active-site residues in the Rab switch II region stabilising the nucleotide-free form differentiate these pathways. (elifesciences.org)
  • These proteins share a core structure, the conserved G-box (GDP/GTP) binding domain, of approximately 170 residues [ 3 ]. (oncotarget.com)
  • Here we define the precise Rab29 binding region of the LRRK2 Armadillo domain between residues 360-450 and show that this domain, termed 'Site #1', can also bind additional LRRK2 substrates, Rab8A and Rab10. (stanford.edu)
  • Rab3 GEP is identical to the human DENN/MADD protein and contains a death domain which can bind the TNFR1 (15). (pancreapedia.org)
  • In the trans-Golgi network (TGN), phosphorylated lysosomal enzymes bind to M-6-P receptors, which direct the enzymes into clathrin-coated vesicles. (biomedcentral.com)
  • 2017). Moreover, Golgi-associated Rab29 can recruit LRRK2 to the surface of the Golgi and activate it there for both auto- and Rab substrate phosphorylation. (stanford.edu)
  • A Rab protein is always bound to another molecule, which determines whether it is inactive or active. (elifesciences.org)
  • Binding to a molecule called GDP makes the Rab protein inactive, while binding to GTP makes it active. (elifesciences.org)
  • Mechanistically, we found that Rab40c binds the protein phosphatase 6 (PP6) complex and ubiquitylates one of its subunits, ankyrin repeat domain 28 (ANKRD28), thus leading to its lysosomal degradation. (life-science-alliance.org)
  • The extracellular signaling protein Sonic hedgehog (Shh) requires dual lipidation for functional signaling, whereby N-terminal palmitoylation is performed by the enzyme Hedgehog acyltransferase (Hhat). (imperial.ac.uk)
  • It is hypothesized that PCAIs work as anticancer agents by disrupting polyisoprenylation-dependent functional interactions of the G-Proteins. (oncotarget.com)
  • These include four regions participating in guanine nucleotide binding, and effector region corresponding to the effector region in Ras, and a CXC prenylation motif at the C-terminal (45). (pancreapedia.org)
  • There are three different protein prenyltransferases in humans: farnesyltransferase (FT) and geranylgeranyltransferase 1 (GGT1) share the same motif (the CaaX box) around the cysteine in their substrates, and are thus called CaaX prenyltransferases, whereas geranylgeranyltransferase 2 (GGT2, also called Rab geranylgeranyltransferase) recognizes a different motif and is thus called a non-CaaX prenyltransferase [ 1 ]. (biomedcentral.com)
  • other download history and gis epistemologies considerations and proteins have normally subsequent and mediate to explore to endocytosis and repair through tyrosine of the ERK and AKT being cells( increased in Parker et al, 2014). (erik-mill.de)
  • Finding effective therapies against cancers driven by mutant and/or overexpressed hyperactive G-proteins remains an area of active research. (oncotarget.com)
  • Resolution of the 3D structure of the TBC/rab GAP domain of GYP1 has shown that it is a fully alpha-helical V-shaped molecule. (embl.de)
  • Taxonomic distribution of proteins containing TBC domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with TBC domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing TBC domain in the selected taxonomic class. (embl.de)
  • RBD, Ras-binding domain of Raf-1. (rupress.org)
  • HECT domain E3 ubiquitin protein li. (gsea-msigdb.org)
  • protein_coding" "Cz10g14210.t1","No alias","Chromochloris zofingiensis","DEAD/DEAH box helicase domain [Interproscan]. (ntu.edu.sg)
  • The experiments showed that different amino acids in the active site of the Rab protein are involved when the GEFs mediate the release of the GDP during the activation process. (elifesciences.org)
  • GTP binding to Ras induces changes in conformation, mainly in two regions named switch I and switch II, that greatly increase the affinity of Ras for its downstream effectors [ 14 ] [ 15 ] . (encyclopedia.pub)
  • protein_coding" "Cz12g19130.t1","No alias","Chromochloris zofingiensis","Clp protease proteolytic subunit /Translocation-enhancing protein TepA [Interproscan]. (ntu.edu.sg)
  • Polyisoprenylated cysteinyl amide inhibitors (PCAIs) are agents that mimic the essential posttranslational modifications of G-proteins. (oncotarget.com)