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RAB27A, member RAS oncogene family

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Target id: 2916

Nomenclature: RAB27A, member RAS oncogene family

Family: RAB subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 221 15q21.3 RAB27A RAB27A, member RAS oncogene family
Mouse - 221 9 40.08 cM Rab27a RAB27A, member RAS oncogene family
Rat - 221 8q24 Rab27a RAB27A, member RAS oncogene family
Previous and Unofficial Names Click here for help
RAB27A
Database Links Click here for help
Alphafold P51159 (Hs), Q9ERI2 (Mm), P23640 (Rn)
ChEMBL Target CHEMBL4105702 (Hs)
Ensembl Gene ENSG00000069974 (Hs), ENSMUSG00000032202 (Mm), ENSRNOG00000052499 (Rn)
Entrez Gene 5873 (Hs), 11891 (Mm), 50645 (Rn)
Human Protein Atlas ENSG00000069974 (Hs)
KEGG Gene hsa:5873 (Hs), mmu:11891 (Mm), rno:50645 (Rn)
OMIM 607624 (Hs)
Pharos P51159 (Hs)
RefSeq Nucleotide NM_004580 (Hs), NM_001301230 (Mm), NM_017317 (Rn)
RefSeq Protein NP_004571 (Hs), NP_001288159 (Mm), NM_017317 (Rn)
UniProtKB P51159 (Hs), Q9ERI2 (Mm), P23640 (Rn)
Wikipedia RAB27A (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
Nexinhib20 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 5.6 pIC50 4
⤷ pIC50 5.6 (IC50 2.6x10-6 M) [4]
Immunopharmacology Comments
Small molecule inhibitors of Rab27a-JFC1 binding, termed Nexinhibs (neutrophil exocytosis inhibitors) demonstrate the druggability of Rab GTPases and inhibition of exocytosis of azurophilic granules in human neutrophils without affecting other important innate immune responses, including phagocytosis and neutrophil extracellular trap production. These thus have potential use as an inhibitor of systemic inflammation [4].
Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   neutrophil (CL:0000775)
Comment:  RAB27A and its effector JFC1 (synaptotagmin like 1) act to regulate neutrophil exocytosis.
References:  1-3
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Antigen presentation
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Griscelli syndrome, type 2
Description: Hypomelanosis with immunologic abnormalities with or without neurologic impairment, is caused by mutation in the RAB27A gene (MIM 603868).
OMIM: 607624

References

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1. Brzezinska AA, Johnson JL, Munafo DB, Crozat K, Beutler B, Kiosses WB, Ellis BA, Catz SD. (2008) The Rab27a effectors JFC1/Slp1 and Munc13-4 regulate exocytosis of neutrophil granules. Traffic, 9 (12): 2151-64. [PMID:18939952]

2. Catz SD. (2014) The role of Rab27a in the regulation of neutrophil function. Cell Microbiol, 16 (9): 1301-10. [PMID:24964030]

3. Johnson JL, Monfregola J, Napolitano G, Kiosses WB, Catz SD. (2012) Vesicular trafficking through cortical actin during exocytosis is regulated by the Rab27a effector JFC1/Slp1 and the RhoA-GTPase-activating protein Gem-interacting protein. Mol Biol Cell, 23 (10): 1902-16. [PMID:22438581]

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]

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