RAB27A, member RAS oncogene family

Target id: 2916

Nomenclature: RAB27A, member RAS oncogene family

Family: RAB subfamily

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     RAB27A, member RAS oncogene family has curated GtoImmuPdb data

Gene and Protein Information
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
RAB27A
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
Nexinhib20 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
GO Annotations:  Associated to 4 GO processes
GO:0043312 neutrophil degranulation TAS
GO:0050766 positive regulation of phagocytosis IMP
click arrow to show/hide IEA associations
GO:0043316 cytotoxic T cell degranulation IEA
GO:0043320 natural killer cell degranulation IEA
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 2 GO processes
GO:0019882 antigen processing and presentation IMP
GO:0050766 positive regulation of phagocytosis IMP
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0097278 complement-dependent cytotoxicity IMP
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 3 GO processes
GO:0043312 neutrophil degranulation TAS
click arrow to show/hide IEA associations
GO:0043316 cytotoxic T cell degranulation IEA
GO:0043320 natural killer cell degranulation IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0043316 cytotoxic T cell degranulation IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0043316 cytotoxic T cell degranulation IEA
Clinically-Relevant Mutations and Pathophysiology
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]

How to cite this page

RAB subfamily: RAB27A, member RAS oncogene family. Last modified on 19/01/2017. Accessed on 16/07/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2916.