RAB GEFs exchange GTP for GDP on RABs (Homo sapiens)

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9, 23, 37, 45, 50...12, 27, 45, 84, 95...52, 53, 128, 132, 143...11, 83, 1313, 22, 45, 63, 99...11, 83, 1317, 13, 18, 20, 24...28, 36, 61, 100, 108...6, 11, 21, 44, 46...45, 54, 84, 111, 118...42, 65, 79, 113, 118...14, 15, 25, 45, 64...19, 35, 40, 45, 55...24, 26, 29, 32, 34...1, 45, 67, 104, 117...31, 34, 36, 38, 45...10, 45, 69, 96, 101...5, 45, 49, 62, 66...17, 21, 41, 45, 88...4, 8, 78, 82, 90...1, 16, 67, 97, 104...2, 33, 39, 143, 177...transport vesicle membranetrans-Golgi network membraneGolgi membranecytoplasmic vesicle membraneendoplasmic reticulum membranesecretory granule membraneearly endosome membranelysosomal membranecytosolmelanosome membranerecycling endosome membraneGDI1 GGC-RAB9:GTPGGC-RAB13 p-T308,S473-AKT1 GDI1 YWHAE CHM GGC-RAB38 GGC-RAB1B GGC-RAB5C GCC-RAB12:GDP:GDIs,CHMsGGC-RAB12 GGC-RAB10 CHML CHML p-S536, S538 DENND1A GGC-RAB31 GTP GDPp-T305,S472-AKT3 TRAPPC12 CHM GDPDENND6A,BGGC-RAB27A GDIs,CHMsCHML GDI2 CHML CHM GDI1 HPS1 GDP GGC-RAB27B TRAPPC6B p-S472,S490-DENND3TRAPPC3 p-S472,S490-DENND3 DENND2D GGC-RAB8B GDI1 GAPVD1 RAB35 GEFsRGP1 RAB3IL1 GGC-RAB7A MON1A TRAPPC8 CHML DENND2A TRAPPC2L GGC-RAB6:GDP:GDIs,CHMsYWHAE dimerGTPGGC-RAB5C GGC-RAB39B GTP GDI1 GDPGGC-RAB3A:GTPRAB3IP CCZ1 RAB9 GEFsGGC-RAB7:GTPDENND5A,BRAB5 GEFsCHM GDIs,CHMsGTPRAB3GAP2 CHM CHM GDP GGC-RAB6A GGC-RAB5B GDI1 GDI2 CHML GTP GTPGGC-RAB9A GTP GDI1 TRAPPC5 RAB32,RAB38:GTPp-T180,S317,S467,S556,S638,T575-ULK1GDI1 GTP RAB31 GEFsDENND3GTPALS2CL GDP CHML GDI1 ATPGGC-RAB31:GTPGGC-RAB3A GDP GDI2 GGC-RAB10 GDP GGC-RAB13:GTPRAB21 GEFsCHM p-2S DENND1B GDI1 CHM HPS1:HPS4RABGEF1 CHM GGC-RAB39B GGC-RAB12:GTPGDPGDPCHM MON1:CCZ1DENND5A MADD GGC-RAB8B GDI2 GGC-RAB9B SBF2 RAB3GAP1 GGC-RAB18:GDP:GDIs,CHMsTRAPPC4 GTPp-T309,S474-AKT2 GDI2 GDP CHM GGC-RAB31:GDP:GDIs,CHMsp-T,p-S-AKTGDI2 RAB8 GEFsCHML GDI2 GGC-RAB6:GTPGDI2 ANKRD27 GDP DENND1C CHM GGC-RAB39:GDP:GDIs,CHMsGDP RAB3GAP1:RAB3GAP2GGC-RAB3A:GDP:GDIs,CHMsRIN1 GGC-RAB14 GGC-RAB7B RINL GDP GTP ST5 YWHAE DENND1A CHM CHML GDIs,CHMsGDI1 GDI1 p-2S DENND1B GDI2 GGC-RAB21 RIN2 CHM GGC-RAB1A GTP TRAPPCsGGC-RAB8A GGC-RAB39A CHML GTPGTP MADDGGC-RAB8:GTPTRAPPC6A CHM DENND6B GGC-RAB14 GGC-RAB1:GTPGAPVD1 DENND4sCHML DENND1C GGC-RAB27A GGC-RAB38 CHM GDP GGC-RAB7B CHML GTP GGC-RAB5A DENND6A GTPGDP GDIs,CHMsRAB3IL1 GTPGDP CHML CHM GGC-RAB21 GGC-RAB13:GDP:GDIs,CHMsGDP GDI2 GGC-RAB9A GDPGDPDENND4B GGC-RAB27B p-S536, S538 DENND1A ADPDENND1B MON1B DENND3GDI1 ADPGGC-RAB6B GDI1 GDI2 GTP GTP GGC-RAB21:GDP:GDIs,CHMsGGC-RAB3A GGC-RAB35:GDP:GDIs,CHMsGDI1 GDPGTPGGC-RAB1:GDP:GDIs,CHMsGGC-RAB6B GDI1 ATPGGC-RAB10:GDP:GDIs,CHMsGDI2 GDIs,CHMsGDI2 RIC1:RGP1CCZ1B GGC-RAB5:GTPGDI2 GGC-RAB18 GGC-RAB5B GGC-RAB14:GDP:GDIs,CHMsGDPGTP GDI2 CHM GGC-RAB6A DENND3 GDP GDI1 TRAPPC13 CHML GGC-RAB18:GTPGGC-RAB35 GGC-RAB32 GGC-RAB8:GDP:GDIs,CHMsGDI2 CHML p-2S-DENND1A,B:YWHAEdimerGDI1 ALS2 GDP GDPGDI1 GDPCHML CHML CHML GTPGTP GDPGDI2 DENND2C GDI2 GDI2 RIC1 GDPCHML CHM GTP GGC-RAB27:GDP:GDIs,CHMsGTPGGC-RAB9:GDP:GDIs,CHMsGGC-RAB39A GTP CHM TRAPPC9 GDI1 GTPDENND1C GGC-RAB1B GGC-RAB39:GTPGGC-RAB9B CHML YWHAE GTPGGC-RAB18 GGC-RAB31 GGC-RAB14:GTPGGC-RAB13 GGC-RAB35:GTPDENND1B RAB13 GEFsGGC-RAB32 TRAPPC11 GDI2 CHM GTP GGC-RAB35 SBF1 GDI2 RIN3 DENND1A, DENND1BGDI1 GDI2 RAB32,RAB38:GDP:GDIs,CHMsCHML GTP GDI1 ST5 GDI1 CHM DENND1A GGC-RAB10:GTPGDI2 p-2S DENND1B p-2S DENND1A,DENND1BHPS4 RIN3 DENND4A DENND4C p-S536, S538 DENND1A GDPCHML GGC-RAB8A RAB3 GEFsCHML GTP GTPTRAPPC10 GGC-RAB5A GGC-RAB7:GDP:GDIs,CHMsCHM GGC-RAB5:GDP:GDIs,CHMsGGC-RAB12 GTPGGC-RAB1A GDIs,CHMsRAB27:GTPGDI2 TRAPPC1 GDP CHML GDI1 DENND5B TRAPPC2 GGC-RAB7A GDP GGC-RAB21:GTPGDP GDPCHM 143


Description

Human cells have more than 60 RAB proteins that are key regulators of intracellular membrane trafficking. These small GTPases contribute to trafficking specificity by localizing to the membranes of different organelles and interacting with effectors such as sorting adaptors, tethering factors, kinases, phosphatases and tubular-vesicular cargo (reviewed in Stenmark et al, 2009; Wandinger-Ness and Zerial, 2014; Zhen and Stenmark, 2015).

RAB localization depends on a number of factors including C-terminal prenylation, the sequence of upstream hypervariable regions and what nucleotide is bound, as well as interaction with RAB-interacting proteins (Chavrier et al, 1991; Ullrich et al, 1993; Soldati et al, 1994; Farnsworth et al, 1994; Seabra, 1996; Wu et al, 2010; reviewed in Stenmark, 2009; Wandinger-Ness and Zerial, 2014). More recently, the activity of RAB GEFs has also been implicated in regulating the localization of RAB proteins (Blumer et al, 2103; Schoebel et al, 2009; Cabrera and Ungermann, 2013; reviewed in Barr, 2013; Zhen and Stenmark, 2015)

In the active, GTP-bound form, RAB proteins are membrane-associated, while in the inactive GDP-bound form, RABs are extracted from the target membrane and exist in a soluble form in complex with GDP dissociation inhibitors (GDIs) (Ullrich et al, 1993; Soldati et al, 1994; Gavriljuk et al, 2013). Conversion between the inactive and active form relies on the activities of RAB guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) (Yoshimura et al, 2010; Wu et al, 2011; Pan et al, 2006; Frasa et al, 2012; reviewed in Stenmark, 2009; Wandinger-Ness and Zerial, 2014; Ishida et al, 2016).

Newly synthesized RABs are bound to a RAB escort protein, CHM (also known as REP1) or CHML (REP2) (Alexandrov et al, 1994; Shen and Seabra, 1996). CHM/REP proteins are the substrate-binding component of the trimeric RAB geranylgeranyltransferase enzyme (GGTaseII) along with the two catalytic subunits RABGGTA and RABGGTB (reviewed in Gutkowska and Swiezewska, 2012; Palsuledesai and Distefano, 2015). REP proteins recruit the unmodified RAB in its GDP-bound state to the GGTase for sequential geranylgeranylation at one or two C-terminal cysteine residues (Alexandrov et al, 1994; Seabra et al 1996; Shen and Seabra, 1996; Baron and Seabra, 2008). After geranylation, CHM/REP proteins remain in complex with the geranylated RAB and escort it to its target membrane, where RAB activity is regulated by GAPs, GEFs, GDIs and membrane-bound GDI displacement factors (GDFs) (Sivars et al, 2003; reviewed in Stenmark, 2009; Wandinger-Ness and Zerial, 2014).

Unlike the RAB GAPS, which (to date) all contain a shared TBC domain, RAB GEFs are structurally diverse and range from monomeric to multisubunit complexes (reviewed in Fukuda et al, 2011; Frasa et al, 2012; Cherfils and Zeghouf, 2013; Ishida et al, 2016). While many GEFs contain one of three conserved GEF domains identified to date - the DENN (differentially expressed in normal and neoplastic cell) domain, the VPS9 domain and the SEC2 domain- other GEFs lack a conserved domain (reviewed in Ishida et al, 2016). Based on sequence conservation and subunit organization, GEFs can be grouped into 6 general classes: the DENND-containing GEFs, the VPS9-containing GEFs (both monomeric), the SEC2-containing GEFs (homodimeric), heterodimeric GEF complexes such as RIC1:RGP1, the multisubunit TRAPPC GEF, and others (reviewed in Barr and Lambright, 2010; Marat et al, 2011; Ishida et al, 2016). GEFs for many RABs have still not been identified, however. View original pathway at:Reactome.

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Pathway is converted from Reactome ID: 8876198
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Reactome Author: Rothfels, Karen

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  94. Ioannou MS, Bell ES, Girard M, Chaineau M, Hamlin JN, Daubaras M, Monast A, Park M, Hodgson L, McPherson PS.; ''DENND2B activates Rab13 at the leading edge of migrating cells and promotes metastatic behavior.''; PubMed
  95. Liewen H, Meinhold-Heerlein I, Oliveira V, Schwarzenbacher R, Luo G, Wadle A, Jung M, Pfreundschuh M, Stenner-Liewen F.; ''Characterization of the human GARP (Golgi associated retrograde protein) complex.''; PubMed
  96. Chen Y, Wang Y, Zhang J, Deng Y, Jiang L, Song E, Wu XS, Hammer JA, Xu T, Lippincott-Schwartz J.; ''Rab10 and myosin-Va mediate insulin-stimulated GLUT4 storage vesicle translocation in adipocytes.''; PubMed
  97. Wong PM, Puente C, Ganley IG, Jiang X.; ''The ULK1 complex: sensing nutrient signals for autophagy activation.''; PubMed
  98. Kouranti I, Sachse M, Arouche N, Goud B, Echard A.; ''Rab35 regulates an endocytic recycling pathway essential for the terminal steps of cytokinesis.''; PubMed
  99. Maretzky T, Reiss K, Ludwig A, Buchholz J, Scholz F, Proksch E, de Strooper B, Hartmann D, Saftig P.; ''ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation.''; PubMed
  100. Wang F, Zhang H, Zhang X, Wang Y, Ren F, Zhang X, Zhai Y, Chang Z.; ''Varp interacts with Rab38 and functions as its potential effector.''; PubMed
  101. Chen YT, Holcomb C, Moore HP.; ''Expression and localization of two low molecular weight GTP-binding proteins, Rab8 and Rab10, by epitope tag.''; PubMed
  102. Baron RA, Seabra MC.; ''Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphate.''; PubMed
  103. Soldati T, Shapiro AD, Svejstrup AB, Pfeffer SR.; ''Membrane targeting of the small GTPase Rab9 is accompanied by nucleotide exchange.''; PubMed
  104. Matsui T, Itoh T, Fukuda M.; ''Small GTPase Rab12 regulates constitutive degradation of transferrin receptor.''; PubMed
  105. Szul T, Sztul E.; ''COPII and COPI traffic at the ER-Golgi interface.''; PubMed
  106. Lord C, Ferro-Novick S, Miller EA.; ''The highly conserved COPII coat complex sorts cargo from the endoplasmic reticulum and targets it to the golgi.''; PubMed
  107. Rodriguez-Gabin AG, Cammer M, Almazan G, Charron M, Larocca JN.; ''Role of rRAB22b, an oligodendrocyte protein, in regulation of transport of vesicles from trans Golgi to endocytic compartments.''; PubMed
  108. Tamura K, Ohbayashi N, Ishibashi K, Fukuda M.; ''Structure-function analysis of VPS9-ankyrin-repeat protein (Varp) in the trafficking of tyrosinase-related protein 1 in melanocytes.''; PubMed
  109. Pan X, Eathiraj S, Munson M, Lambright DG.; ''TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism.''; PubMed
  110. Pusapati GV, Luchetti G, Pfeffer SR.; ''Ric1-Rgp1 complex is a guanine nucleotide exchange factor for the late Golgi Rab6A GTPase and an effector of the medial Golgi Rab33B GTPase.''; PubMed
  111. Díaz E, Pfeffer SR.; ''TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking.''; PubMed
  112. Ozeki S, Cheng J, Tauchi-Sato K, Hatano N, Taniguchi H, Fujimoto T.; ''Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane.''; PubMed
  113. Burgo A, Sotirakis E, Simmler MC, Verraes A, Chamot C, Simpson JC, Lanzetti L, Proux-Gillardeaux V, Galli T.; ''Role of Varp, a Rab21 exchange factor and TI-VAMP/VAMP7 partner, in neurite growth.''; PubMed
  114. Wasmeier C, Romao M, Plowright L, Bennett DC, Raposo G, Seabra MC.; ''Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes.''; PubMed
  115. Geppert M, Bolshakov VY, Siegelbaum SA, Takei K, De Camilli P, Hammer RE, Südhof TC.; ''The role of Rab3A in neurotransmitter release.''; PubMed
  116. Chen Y, Lippincott-Schwartz J.; ''Rab10 delivers GLUT4 storage vesicles to the plasma membrane.''; PubMed
  117. Xu J, Fotouhi M, McPherson PS.; ''Phosphorylation of the exchange factor DENND3 by ULK in response to starvation activates Rab12 and induces autophagy.''; PubMed
  118. Ishida M, E Oguchi M, Fukuda M.; ''Multiple Types of Guanine Nucleotide Exchange Factors (GEFs) for Rab Small GTPases.''; PubMed
  119. Marat AL, McPherson PS.; ''The connecdenn family, Rab35 guanine nucleotide exchange factors interfacing with the clathrin machinery.''; PubMed
  120. Stenmark H.; ''Rab GTPases as coordinators of vesicle traffic.''; PubMed
  121. Klinkert K, Echard A.; ''Rab35 GTPase: A Central Regulator of Phosphoinositides and F-actin in Endocytic Recycling and Beyond.''; PubMed
  122. Siniossoglou S, Pelham HR.; ''An effector of Ypt6p binds the SNARE Tlg1p and mediates selective fusion of vesicles with late Golgi membranes.''; PubMed
  123. Ohbayashi N, Yatsu A, Tamura K, Fukuda M.; ''The Rab21-GEF activity of Varp, but not its Rab32/38 effector function, is required for dendrite formation in melanocytes.''; PubMed
  124. Pérez-Victoria FJ, Bonifacino JS.; ''Dual roles of the mammalian GARP complex in tethering and SNARE complex assembly at the trans-golgi network.''; PubMed
  125. Kachaner D, Filipe J, Laplantine E, Bauch A, Bennett KL, Superti-Furga G, Israël A, Weil R.; ''Plk1-dependent phosphorylation of optineurin provides a negative feedback mechanism for mitotic progression.''; PubMed
  126. Wang CW, Stromhaug PE, Shima J, Klionsky DJ.; ''The Ccz1-Mon1 protein complex is required for the late step of multiple vacuole delivery pathways.''; PubMed
  127. Allaire PD, Marat AL, Dall'Armi C, Di Paolo G, McPherson PS, Ritter B.; ''The Connecdenn DENN domain: a GEF for Rab35 mediating cargo-specific exit from early endosomes.''; PubMed
  128. Fukuda M.; ''Rab27 effectors, pleiotropic regulators in secretory pathways.''; PubMed
  129. Poteryaev D, Datta S, Ackema K, Zerial M, Spang A.; ''Identification of the switch in early-to-late endosome transition.''; PubMed
  130. Rahajeng J, Giridharan SS, Cai B, Naslavsky N, Caplan S.; ''MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a.''; PubMed
  131. Davey JR, Humphrey SJ, Junutula JR, Mishra AK, Lambright DG, James DE, Stöckli J.; ''TBC1D13 is a RAB35 specific GAP that plays an important role in GLUT4 trafficking in adipocytes.''; PubMed
  132. Mahoney TR, Liu Q, Itoh T, Luo S, Hadwiger G, Vincent R, Wang ZW, Fukuda M, Nonet ML.; ''Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis elegans.''; PubMed
  133. Bao X, Faris AE, Jang EK, Haslam RJ.; ''Molecular cloning, bacterial expression and properties of Rab31 and Rab32.''; PubMed
  134. Westlake CJ, Baye LM, Nachury MV, Wright KJ, Ervin KE, Phu L, Chalouni C, Beck JS, Kirkpatrick DS, Slusarski DC, Sheffield VC, Scheller RH, Jackson PK.; ''Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosome.''; PubMed
  135. Ortiz Sandoval C, Simmen T.; ''Rab proteins of the endoplasmic reticulum: functions and interactors.''; PubMed
  136. Bultema JJ, Di Pietro SM.; ''Cell type-specific Rab32 and Rab38 cooperate with the ubiquitous lysosome biogenesis machinery to synthesize specialized lysosome-related organelles.''; PubMed
  137. Palsuledesai CC, Distefano MD.; ''Protein prenylation: enzymes, therapeutics, and biotechnology applications.''; PubMed
  138. Sun Y, Bilan PJ, Liu Z, Klip A.; ''Rab8A and Rab13 are activated by insulin and regulate GLUT4 translocation in muscle cells.''; PubMed
  139. Gutkowska M, Swiezewska E.; ''Structure, regulation and cellular functions of Rab geranylgeranyl transferase and its cellular partner Rab Escort Protein.''; PubMed
  140. Nishikimi A, Ishihara S, Ozawa M, Etoh K, Fukuda M, Kinashi T, Katagiri K.; ''Rab13 acts downstream of the kinase Mst1 to deliver the integrin LFA-1 to the cell surface for lymphocyte trafficking.''; PubMed
  141. Kajiho H, Sakurai K, Minoda T, Yoshikawa M, Nakagawa S, Fukushima S, Kontani K, Katada T.; ''Characterization of RIN3 as a guanine nucleotide exchange factor for the Rab5 subfamily GTPase Rab31.''; PubMed
  142. Ishikura S, Klip A.; ''Muscle cells engage Rab8A and myosin Vb in insulin-dependent GLUT4 translocation.''; PubMed
  143. Yoshimura S, Gerondopoulos A, Linford A, Rigden DJ, Barr FA.; ''Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors.''; PubMed
  144. Brunet S, Sacher M.; ''In sickness and in health: the role of TRAPP and associated proteins in disease.''; PubMed
  145. Ioannou MS, McPherson PS.; ''Regulation of Cancer Cell Behavior by the Small GTPase Rab13.''; PubMed
  146. Chavrier P, Gorvel JP, Stelzer E, Simons K, Gruenberg J, Zerial M.; ''Hypervariable C-terminal domain of rab proteins acts as a targeting signal.''; PubMed
  147. Suzuki-Utsunomiya K, Hadano S, Otomo A, Kunita R, Mizumura H, Osuga H, Ikeda JE.; ''ALS2CL, a novel ALS2-interactor, modulates ALS2-mediated endosome dynamics.''; PubMed
  148. Siniossoglou S, Peak-Chew SY, Pelham HR.; ''Ric1p and Rgp1p form a complex that catalyses nucleotide exchange on Ypt6p.''; PubMed
  149. Harrison RE, Bucci C, Vieira OV, Schroer TA, Grinstein S.; ''Phagosomes fuse with late endosomes and/or lysosomes by extension of membrane protrusions along microtubules: role of Rab7 and RILP.''; PubMed
  150. Reiss K, Maretzky T, Ludwig A, Tousseyn T, de Strooper B, Hartmann D, Saftig P.; ''ADAM10 cleavage of N-cadherin and regulation of cell-cell adhesion and beta-catenin nuclear signalling.''; PubMed
  151. Handley MT, Morris-Rosendahl DJ, Brown S, Macdonald F, Hardy C, Bem D, Carpanini SM, Borck G, Martorell L, Izzi C, Faravelli F, Accorsi P, Pinelli L, Basel-Vanagaite L, Peretz G, Abdel-Salam GM, Zaki MS, Jansen A, Mowat D, Glass I, Stewart H, Mancini G, Lederer D, Roscioli T, Giuliano F, Plomp AS, Rolfs A, Graham JM, Seemanova E, Poo P, García-Cazorla A, Edery P, Jackson IJ, Maher ER, Aligianis IA.; ''Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome.''; PubMed
  152. Köhler K, Louvard D, Zahraoui A.; ''Rab13 regulates PKA signaling during tight junction assembly.''; PubMed
  153. Sakane A, Honda K, Sasaki T.; ''Rab13 regulates neurite outgrowth in PC12 cells through its effector protein, JRAB/MICAL-L2.''; PubMed
  154. Schuck S, Gerl MJ, Ang A, Manninen A, Keller P, Mellman I, Simons K.; ''Rab10 is involved in basolateral transport in polarized Madin-Darby canine kidney cells.''; PubMed
  155. Sung CH, Leroux MR.; ''The roles of evolutionarily conserved functional modules in cilia-related trafficking.''; PubMed
  156. Pan Y, Zhang Y, Chen L, Liu Y, Feng Y, Yan J.; ''The Critical Role of Rab31 in Cell Proliferation and Apoptosis in Cancer Progression.''; PubMed
  157. Soga T, Matsumoto Si, Oda T, Saito T, Hiyama H, Takasaki J, Kamohara M, Ohishi T, Matsushime H, Furuichi K.; ''Molecular cloning and characterization of prokineticin receptors.''; PubMed
  158. Miserey-Lenkei S, Colombo MI.; ''Small RAB GTPases Regulate Multiple Steps of Mitosis.''; PubMed
  159. Luo HR, Saiardi A, Nagata E, Ye K, Yu H, Jung TS, Luo X, Jain S, Sawa A, Snyder SH.; ''GRAB: a physiologic guanine nucleotide exchange factor for Rab3A, which interacts with inositol hexakisphosphate kinase.''; PubMed
  160. Horiuchi H, Lippé R, McBride HM, Rubino M, Woodman P, Stenmark H, Rybin V, Wilm M, Ashman K, Mann M, Zerial M.; ''A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function.''; PubMed
  161. Balderhaar HJ, Ungermann C.; ''CORVET and HOPS tethering complexes - coordinators of endosome and lysosome fusion.''; PubMed
  162. Espinosa EJ, Calero M, Sridevi K, Pfeffer SR.; ''RhoBTB3: a Rho GTPase-family ATPase required for endosome to Golgi transport.''; PubMed
  163. Jean S, Cox S, Nassari S, Kiger AA.; ''Starvation-induced MTMR13 and RAB21 activity regulates VAMP8 to promote autophagosome-lysosome fusion.''; PubMed
  164. Nordmann M, Cabrera M, Perz A, Bröcker C, Ostrowicz C, Engelbrecht-Vandré S, Ungermann C.; ''The Mon1-Ccz1 complex is the GEF of the late endosomal Rab7 homolog Ypt7.''; PubMed
  165. Fukui K, Sasaki T, Imazumi K, Matsuura Y, Nakanishi H, Takai Y.; ''Isolation and characterization of a GTPase activating protein specific for the Rab3 subfamily of small G proteins.''; PubMed
  166. Linford A, Yoshimura S, Nunes Bastos R, Langemeyer L, Gerondopoulos A, Rigden DJ, Barr FA.; ''Rab14 and its exchange factor FAM116 link endocytic recycling and adherens junction stability in migrating cells.''; PubMed
  167. Gerondopoulos A, Bastos RN, Yoshimura S, Anderson R, Carpanini S, Aligianis I, Handley MT, Barr FA.; ''Rab18 and a Rab18 GEF complex are required for normal ER structure.''; PubMed
  168. Knödler A, Feng S, Zhang J, Zhang X, Das A, Peränen J, Guo W.; ''Coordination of Rab8 and Rab11 in primary ciliogenesis.''; PubMed
  169. Kondo H, Shirakawa R, Higashi T, Kawato M, Fukuda M, Kita T, Horiuchi H.; ''Constitutive GDP/GTP exchange and secretion-dependent GTP hydrolysis activity for Rab27 in platelets.''; PubMed
  170. Wu YW, Oesterlin LK, Tan KT, Waldmann H, Alexandrov K, Goody RS.; ''Membrane targeting mechanism of Rab GTPases elucidated by semisynthetic protein probes.''; PubMed
  171. Wang J, Morita Y, Mazelova J, Deretic D.; ''The Arf GAP ASAP1 provides a platform to regulate Arf4- and Rab11-Rab8-mediated ciliary receptor targeting.''; PubMed
  172. Nokes RL, Fields IC, Collins RN, Fölsch H.; ''Rab13 regulates membrane trafficking between TGN and recycling endosomes in polarized epithelial cells.''; PubMed
  173. Loftus SK, Larson DM, Baxter LL, Antonellis A, Chen Y, Wu X, Jiang Y, Bittner M, Hammer JA, Pavan WJ.; ''Mutation of melanosome protein RAB38 in chocolate mice.''; PubMed
  174. Alexandrov K, Horiuchi H, Steele-Mortimer O, Seabra MC, Zerial M.; ''Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes.''; PubMed
  175. Barr F, Lambright DG.; ''Rab GEFs and GAPs.''; PubMed
  176. Mahadevan D, Spier C, Della Croce K, Miller S, George B, Riley C, Warner S, Grogan TM, Miller TP.; ''Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures.''; PubMed
  177. Miller VJ, Sharma P, Kudlyk TA, Frost L, Rofe AP, Watson IJ, Duden R, Lowe M, Lupashin VV, Ungar D.; ''Molecular insights into vesicle tethering at the Golgi by the conserved oligomeric Golgi (COG) complex and the golgin TATA element modulatory factor (TMF).''; PubMed
  178. Burgo A, Proux-Gillardeaux V, Sotirakis E, Bun P, Casano A, Verraes A, Liem RK, Formstecher E, Coppey-Moisan M, Galli T.; ''A molecular network for the transport of the TI-VAMP/VAMP7 vesicles from cell center to periphery.''; PubMed
  179. Sun Y, Jaldin-Fincati J, Liu Z, Bilan PJ, Klip A.; ''A complex of Rab13 with MICAL-L2 and α-actinin-4 is essential for insulin-dependent GLUT4 exocytosis.''; PubMed
  180. Liu S, Storrie B.; ''Are Rab proteins the link between Golgi organization and membrane trafficking?''; PubMed
  181. Morimoto S, Nishimura N, Terai T, Manabe S, Yamamoto Y, Shinahara W, Miyake H, Tashiro S, Shimada M, Sasaki T.; ''Rab13 mediates the continuous endocytic recycling of occludin to the cell surface.''; PubMed
  182. Pellinen T, Arjonen A, Vuoriluoto K, Kallio K, Fransen JA, Ivaska J.; ''Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of beta1-integrins.''; PubMed
  183. Marat AL, Dokainish H, McPherson PS.; ''DENN domain proteins: regulators of Rab GTPases.''; PubMed
  184. Kapfhamer D, Valladares O, Sun Y, Nolan PM, Rux JJ, Arnold SE, Veasey SC, Bućan M.; ''Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse.''; PubMed
  185. Pérez-Victoria FJ, Mardones GA, Bonifacino JS.; ''Requirement of the human GARP complex for mannose 6-phosphate-receptor-dependent sorting of cathepsin D to lysosomes.''; PubMed
  186. Reiter JF, Blacque OE, Leroux MR.; ''The base of the cilium: roles for transition fibres and the transition zone in ciliary formation, maintenance and compartmentalization.''; PubMed
  187. English AR, Voeltz GK.; ''Rab10 GTPase regulates ER dynamics and morphology.''; PubMed
  188. Matsui T, Fukuda M.; ''Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4.''; PubMed
  189. Sivars U, Aivazian D, Pfeffer SR.; ''Yip3 catalyses the dissociation of endosomal Rab-GDI complexes.''; PubMed
  190. Fukuda M.; ''Multiple Roles of VARP in Endosomal Trafficking: Rabs, Retromer Components and R-SNARE VAMP7 Meet on VARP.''; PubMed
  191. Lu R, Johnson DL, Stewart L, Waite K, Elliott D, Wilson JM.; ''Rab14 regulation of claudin-2 trafficking modulates epithelial permeability and lumen morphogenesis.''; PubMed
  192. Gutierrez MG, Munafó DB, Berón W, Colombo MI.; ''Rab7 is required for the normal progression of the autophagic pathway in mammalian cells.''; PubMed
  193. Rabquer BJ, Amin MA, Teegala N, Shaheen MK, Tsou PS, Ruth JH, Lesch CA, Imhof BA, Koch AE.; ''Junctional adhesion molecule-C is a soluble mediator of angiogenesis.''; PubMed
  194. Xu J, McPherson PS.; ''DENND3: a signaling/trafficking interface in autophagy.''; PubMed
  195. Zhang X, He X, Fu XY, Chang Z.; ''Varp is a Rab21 guanine nucleotide exchange factor and regulates endosome dynamics.''; PubMed
  196. Tamura K, Ohbayashi N, Maruta Y, Kanno E, Itoh T, Fukuda M.; ''Varp is a novel Rab32/38-binding protein that regulates Tyrp1 trafficking in melanocytes.''; PubMed
  197. Sirohi K, Chalasani ML, Sudhakar C, Kumari A, Radha V, Swarup G.; ''M98K-OPTN induces transferrin receptor degradation and RAB12-mediated autophagic death in retinal ganglion cells.''; PubMed
  198. Rodriguez-Gabin AG, Yin X, Si Q, Larocca JN.; ''Transport of mannose-6-phosphate receptors from the trans-Golgi network to endosomes requires Rab31.''; PubMed
  199. Cantalupo G, Alifano P, Roberti V, Bruni CB, Bucci C.; ''Rab-interacting lysosomal protein (RILP): the Rab7 effector required for transport to lysosomes.''; PubMed
  200. Cherfils J, Zeghouf M.; ''Regulation of small GTPases by GEFs, GAPs, and GDIs.''; PubMed

History

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CompareRevisionActionTimeUserComment
101400view11:28, 1 November 2018ReactomeTeamreactome version 66
100938view21:04, 31 October 2018ReactomeTeamreactome version 65
100475view19:38, 31 October 2018ReactomeTeamreactome version 64
100020view16:22, 31 October 2018ReactomeTeamreactome version 63
99573view14:55, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93395view11:22, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

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<
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
ALS2 ProteinQ96Q42 (Uniprot-TrEMBL)
ALS2CL ProteinQ60I27 (Uniprot-TrEMBL)
ANKRD27 ProteinQ96NW4 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
CCZ1 ProteinP86791 (Uniprot-TrEMBL)
CCZ1B ProteinP86790 (Uniprot-TrEMBL)
CHM ProteinP24386 (Uniprot-TrEMBL)
CHML ProteinP26374 (Uniprot-TrEMBL)
DENND1A ProteinQ8TEH3 (Uniprot-TrEMBL)
DENND1A, DENND1BComplexR-HSA-8933359 (Reactome)
DENND1B ProteinQ6P3S1 (Uniprot-TrEMBL)
DENND1C ProteinQ8IV53 (Uniprot-TrEMBL)
DENND2A ProteinQ9ULE3 (Uniprot-TrEMBL)
DENND2C ProteinQ68D51 (Uniprot-TrEMBL)
DENND2D ProteinQ9H6A0 (Uniprot-TrEMBL)
DENND3 ProteinA2RUS2 (Uniprot-TrEMBL)
DENND3ProteinA2RUS2 (Uniprot-TrEMBL)
DENND3ComplexR-HSA-8876437 (Reactome)
DENND4A ProteinQ7Z401 (Uniprot-TrEMBL)
DENND4B ProteinO75064 (Uniprot-TrEMBL)
DENND4C ProteinQ5VZ89 (Uniprot-TrEMBL)
DENND4sComplexR-HSA-8876092 (Reactome)
DENND5A ProteinQ6IQ26 (Uniprot-TrEMBL)
DENND5A,BComplexR-HSA-8877802 (Reactome)
DENND5B ProteinQ6ZUT9 (Uniprot-TrEMBL)
DENND6A ProteinQ8IWF6 (Uniprot-TrEMBL)
DENND6A,BComplexR-HSA-8876608 (Reactome)
DENND6B ProteinQ8NEG7 (Uniprot-TrEMBL)
GAPVD1 ProteinQ14C86 (Uniprot-TrEMBL)
GCC-RAB12:GDP:GDIs,CHMsComplexR-HSA-8876453 (Reactome)
GDI1 ProteinP31150 (Uniprot-TrEMBL)
GDI2 ProteinP50395 (Uniprot-TrEMBL)
GDIs,CHMsComplexR-HSA-8875305 (Reactome)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GGC-RAB10 ProteinP61026 (Uniprot-TrEMBL)
GGC-RAB10:GDP:GDIs,CHMsComplexR-HSA-8876131 (Reactome)
GGC-RAB10:GTPComplexR-HSA-8876128 (Reactome)
GGC-RAB12 ProteinQ6IQ22 (Uniprot-TrEMBL)
GGC-RAB12:GTPComplexR-HSA-8876448 (Reactome)
GGC-RAB13 ProteinP51153 (Uniprot-TrEMBL)
GGC-RAB13:GDP:GDIs,CHMsComplexR-HSA-8876604 (Reactome)
GGC-RAB13:GTPComplexR-HSA-8876599 (Reactome)
GGC-RAB14 ProteinP61106 (Uniprot-TrEMBL)
GGC-RAB14:GDP:GDIs,CHMsComplexR-HSA-8876596 (Reactome)
GGC-RAB14:GTPComplexR-HSA-8876595 (Reactome)
GGC-RAB18 ProteinQ9NP72 (Uniprot-TrEMBL)
GGC-RAB18:GDP:GDIs,CHMsComplexR-HSA-8877994 (Reactome)
GGC-RAB18:GTPComplexR-HSA-8877989 (Reactome)
GGC-RAB1:GDP:GDIs,CHMsComplexR-HSA-8877473 (Reactome)
GGC-RAB1:GTPComplexR-HSA-8877468 (Reactome)
GGC-RAB1A ProteinP62820 (Uniprot-TrEMBL)
GGC-RAB1B ProteinQ9H0U4 (Uniprot-TrEMBL)
GGC-RAB21 ProteinQ9UL25 (Uniprot-TrEMBL)
GGC-RAB21:GDP:GDIs,CHMsComplexR-HSA-8876836 (Reactome)
GGC-RAB21:GTPComplexR-HSA-8876838 (Reactome)
GGC-RAB27:GDP:GDIs,CHMsComplexR-HSA-8877298 (Reactome)
GGC-RAB27A ProteinP51159 (Uniprot-TrEMBL)
GGC-RAB27B ProteinO00194 (Uniprot-TrEMBL)
GGC-RAB31 ProteinQ13636 (Uniprot-TrEMBL)
GGC-RAB31:GDP:GDIs,CHMsComplexR-HSA-8877287 (Reactome)
GGC-RAB31:GTPComplexR-HSA-8877284 (Reactome)
GGC-RAB32 ProteinQ13637 (Uniprot-TrEMBL)
GGC-RAB35 ProteinQ15286 (Uniprot-TrEMBL)
GGC-RAB35:GDP:GDIs,CHMsComplexR-HSA-8877604 (Reactome)
GGC-RAB35:GTPComplexR-HSA-8877601 (Reactome)
GGC-RAB38 ProteinP57729 (Uniprot-TrEMBL)
GGC-RAB39:GDP:GDIs,CHMsComplexR-HSA-8877806 (Reactome)
GGC-RAB39:GTPComplexR-HSA-8877804 (Reactome)
GGC-RAB39A ProteinQ14964 (Uniprot-TrEMBL)
GGC-RAB39B ProteinQ96DA2 (Uniprot-TrEMBL)
GGC-RAB3A ProteinP20336 (Uniprot-TrEMBL)
GGC-RAB3A:GDP:GDIs,CHMsComplexR-HSA-8875313 (Reactome)
GGC-RAB3A:GTPComplexR-HSA-8875326 (Reactome)
GGC-RAB5:GDP:GDIs,CHMsComplexR-HSA-8875330 (Reactome)