RAB subfamily | Enzymes | IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY

RAB subfamily C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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The Rab family of proteins is a member of the Ras superfamily of monomeric G proteins. Rab GTPases regulate many steps of membrane traffic, 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 ( see HGNC RAB, 65 genes ).

Enzymes

Targets of relevance to immunopharmacology are highlighted in blue

RAB27A, member RAS oncogene family Show summary »« Hide summary More detailed page go icon to follow link

RAB32, member RAS oncogene family Show summary »« Hide summary

Target Id	3292
Nomenclature	RAB32, member RAS oncogene family
Genes	RAB32 (Hs), Rab32 (Mm), Rab32 (Rn)
Ensembl ID	ENSG00000118508 (Hs), ENSMUSG00000019832 (Mm), ENSRNOG00000014258 (Rn)
UniProtKB AC	Q13637 (Hs), Q3TXU7 (Mm)
Comment	A genetic variant encoding a S71R substitution in the RAB32 small GTPase has been identified as a risk factor in familial Parkinson's disease [3]. RAB32^S71R appears to increase leucine rich repeat kinase 2 (LRRK2) autophosphorylation and kinase activity. Activating mutations in LRRK2 are already known to be associated with the pathobiology of the disease [1-2,6], with pharmacological inhibitors of LRRK2 being evaluated for clinical potential [5].

References

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1. Alessi DR, Pfeffer SR. (2024) Leucine-Rich Repeat Kinases. Annu Rev Biochem, 93 (1): 261-287. [PMID:38621236]

2. El Otmani H, Daghi M, Tahiri Jouti N, Lesage S. (2023) An overview of the worldwide distribution of LRRK2 mutations in Parkinson's disease. Neurodegener Dis Manag, 13 (6): 335-350. [PMID:38305913]

3. Hop PJ, Lai D, Keagle PJ, Baron DM, Kenna BJ, Kooyman M, Shankaracharya, Halter C, Straniero L, Asselta R et al.. (2024) Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson's disease. Nat Genet, 56 (7): 1371-1376. [PMID:38858457]

4. Johnson JL, Ramadass M, He J, Brown SJ, Zhang J, Abgaryan L, Biris N, Gavathiotis E, Rosen H, Catz SD. (2016) Identification of Neutrophil Exocytosis Inhibitors (Nexinhibs), Small Molecule Inhibitors of Neutrophil Exocytosis and Inflammation: DRUGGABILITY OF THE SMALL GTPase Rab27a. J Biol Chem, 291 (50): 25965-25982. [PMID:27702998]

5. Komori T, Kuwahara T. (2023) An Update on the Interplay between LRRK2, Rab GTPases and Parkinson's Disease. Biomolecules, 13 (11). [PMID:38002327]

6. Navarro E, Efthymiou AG, Parks M, Riboldi GM, Vialle RA, Udine E, Muller BZ, Humphrey J, Allan A, Argyrou CC et al.. (2024) LRRK2 G2019S variant is associated with transcriptional changes in Parkinson's disease human myeloid cells under proinflammatory environment. bioRxiv,. [PMID:38854101]

How to cite this family page

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Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.