Ras-related protein Rab: Difference between revisions

Revision as of 13:34, 4 August 2024

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].

Disease

Rab-11A, Rab-11B and Rab-25 are associated with Alzheimer disease, Huntington disease, type 2 diabetes and cancer^[7].

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^[8]. 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

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Bhuin T, Roy JK. Rab11 in disease progression. Int J Mol Cell Med. 2015 Winter;4(1):1-8. PMID:25815277
↑ 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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Michal Harel, Alexander Berchansky

[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] Bhuin T, Roy JK. Rab11 in disease progression. Int J Mol Cell Med. 2015 Winter;4(1):1-8. PMID:25815277

[8] 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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 *'''Rab-3B''' is essential for the transportation and secretion within cells and its expression is linked to progression of various malignancies<ref>PMID:38688977</ref>.
 *'''Rab-3C''' promotes vesicle formation and packaging<ref>PMID:36652260</ref>.
+*'''Rab-3D''' regulates intracellular vesicle transport during exocytosis<ref>PMID:12168804</ref>.
 == Disease ==