Proteopedia

Ras-related protein Rab

Revision as of 11:03, 5 August 2024 by Michal Harel (talk | contribs)


Function

Ras-related protein Rab belongs to the Rab family of the small GTPase superfamily. It is associated with both constitutive and regulated secretory pathways and with pathways regulating protein traffic. Rab cycles between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors responsible for vesicle formation, movement, tethering and fusion.

  • Rab-1A is required in stress-induced autophagy[1].
  • Rab-1B is required for secretion.
  • Rab-2B regulates Golgi morphology[2].
  • Rab-3A is abundant in the brain and plays a role in recruitment of synaptic vesicles for exocytosis[3].
  • Rab-3B is essential for the transportation and secretion within cells and its expression is linked to progression of various malignancies[4].
  • Rab-3C promotes vesicle formation and packaging[5].
  • Rab-3D regulates intracellular vesicle transport during exocytosis[6].
  • Rab-4 regulates recycling vesicle formation[7].
  • Rab-5A regulates early endoscope fusion[8].
  • Rab-6A regulates vesicular trafficking within there Golgi and non-Golgi compartments[9].

Disease

Rab-11A, Rab-11B and Rab-25 are associated with Alzheimer disease, Huntington disease, type 2 diabetes and cancer[10].

Structural highlights

Rab-11A undergoes a conformation change of between its inactive GDP-bound structure and its active GTP-bound structure. located at the surface of the protein[11]. Water molecules are shown as red spheres.

Ras-related protein Rab 3D structures


Human Rab-11A complex with GDP, phosphate and Mg+2 ion (green) (PDB code 1oix)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Gyurkovska V, Murtazina R, Zhao SF, Shikano S, Okamoto Y, Segev N. Dual function of Rab1A in secretion and autophagy: hypervariable domain dependence. Life Sci Alliance. 2023 Feb 13;6(5):e202201810. PMID:36781179 doi:10.26508/lsa.202201810
  2. ↑ Aizawa M, Fukuda M. Small GTPase Rab2B and Its Specific Binding Protein Golgi-associated Rab2B Interactor-like 4 (GARI-L4) Regulate Golgi Morphology. J Biol Chem. 2015 Sep 4;290(36):22250-61. PMID:26209634 doi:10.1074/jbc.M115.669242
  3. ↑ Geppert M, Bolshakov VY, Siegelbaum SA, Takei K, De Camilli P, Hammer RE, Südhof TC. The role of Rab3A in neurotransmitter release. Nature. 1994 Jun 9;369(6480):493-7. PMID:7911226 doi:10.1038/369493a0
  4. ↑ Liu XS, Chen YL, Chen YX, Wu RM, Tan F, Wang YL, Liu ZY, Gao Y, Pei ZJ. Pan-cancer analysis reveals correlation between RAB3B expression and tumor heterogeneity, immune microenvironment, and prognosis in multiple cancers. Sci Rep. 2024 Apr 30;14(1):9881. PMID:38688977 doi:10.1038/s41598-024-60581-x
  5. ↑ Chang YC, Li CH, Chan MH, Fang CY, Zhang ZX, Chen CL, Hsiao M. Overexpression of synaptic vesicle protein Rab GTPase 3C promotes vesicular exocytosis and drug resistance in colorectal cancer cells. Mol Oncol. 2023 Mar;17(3):422-444. PMID:36652260 doi:10.1002/1878-0261.13378
  6. ↑ Millar AL, Pavios NJ, Xu J, Zheng MH. Rab3D: a regulator of exocytosis in non-neuronal cells. Histol Histopathol. 2002;17(3):929-36. PMID:12168804 doi:10.14670/HH-17.929
  7. ↑ Mohrmann K, Gerez L, Oorschot V, Klumperman J, van der Sluijs P. Rab4 function in membrane recycling from early endosomes depends on a membrane to cytoplasm cycle. J Biol Chem. 2002 Aug 30;277(35):32029-35. PMID:12036958 doi:10.1074/jbc.M203064200
  8. ↑ Khan FI, Aamir M, Wei DQ, Ahmad F, Hassan MI. Molecular mechanism of Ras-related protein Rab-5A and effect of mutations in the catalytically active phosphate-binding loop. J Biomol Struct Dyn. 2017 Jan;35(1):105-118. PMID:26727234 doi:10.1080/07391102.2015.1134346
  9. ↑ Del Nery E, Miserey-Lenkei S, Falguières T, Nizak C, Johannes L, Perez F, Goud B. Rab6A and Rab6A' GTPases play non-overlapping roles in membrane trafficking. Traffic. 2006 Apr;7(4):394-407. PMID:16536738 doi:10.1111/j.1600-0854.2006.00395.x
  10. ↑ Bhuin T, Roy JK. Rab11 in disease progression. Int J Mol Cell Med. 2015 Winter;4(1):1-8. PMID:25815277
  11. ↑ Pasqualato S, Senic-Matuglia F, Renault L, Goud B, Salamero J, Cherfils J. The structural GDP/GTP cycle of Rab11 reveals a novel interface involved in the dynamics of recycling endosomes. J Biol Chem. 2004 Mar 19;279(12):11480-8. Epub 2003 Dec 29. PMID:14699104 doi:10.1074/jbc.M310558200

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