RAB4B

RAB4B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2O52
Identifiers
Aliases	RAB4B , member RAS oncogene family
External IDs	OMIM: 612945; MGI: 105071; HomoloGene: 100632; GeneCards: RAB4B; OMA:RAB4B - orthologs
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19q13.2 Start 40,778,216 bp [1] End 40,796,942 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7 A3|7 15.84 cM Start 26,867,849 bp [2] End 26,878,321 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in C1 segment granulocyte primary visual cortex substantia nigra Brodmann area 9 monocyte hippocampus proper hypothalamus putamen right frontal lobe Top expressed in granulocyte spleen islet of Langerhans cerebellar cortex adrenal gland superior frontal gyrus primary visual cortex hippocampus proper striatum of neuraxis thymus More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding GTP binding GTPase activity protein binding molecular function Cellular component perinuclear region of cytoplasm recycling endosome insulin-responsive compartment membrane plasma membrane secretory granule membrane endosome Biological process protein transport regulation of endocytosis glucose import neutrophil degranulation intracellular protein transport Rab protein signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 53916 19342 Ensembl ENSG00000167578 ENSMUSG00000053291 UniProt P61018 Q91ZR1 RefSeq (mRNA) NM_016154 NM_029391 RefSeq (protein) NP_057238 NP_083667 Location (UCSC) Chr 19: 40.78 – 40.8 Mb Chr 7: 26.87 – 26.88 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ras-related protein Rab-4B is a protein that in humans is encoded by the RAB4B gene. ^{[5] [6] [7]}

Ras-related protein Rab-4B is involved in the vesicle recycling process of endocytosis. Eukaryotic cells uptake cargo from their external environment via donor vesicle budding and fusion of the bud with its target cell membrane. Many proteins are required to maintain homeostasis through this process and to tightly regulate the transport, docking and recycling of materials within the cell. Rab-4B proteins contribute to the regulation of endocytotic recycling in order to control vesicular trafficking. ^{[8] [9] [10]}

Function

RAB proteins are a family of small GTPases that play a role in vesicular transportation regulation. Rab-4B has been shown to be localized to the initial stages of endocytosis, through its interaction with the early endosome. ^{[11] [12]}

Shows the role of RAB4B in its interactions with the early endosome.

In addition, Rab-4B is thought to be important in the insulin pathway with its involvement with GLUT4 trafficking. GLUT4 plays a crucial role in maintaining glucose balance, and is primarily found in cells that respond to insulin for glucose uptake, such as adipocytes. Upon stimulation by insulin, RAB-4B is activated and able to contribute to the translocation of GLUT4 to the cell membrane, facilitating glucose uptake. ^{[10] [13]}

RAB-4B has been shown to contribute to the recycling of transferrin receptors through the early endosome interaction. ^[14]

Interactions

Rab-4B has also been shown to interact with kinesin and dynein motor proteins during endocytosis and exocytosis. KIF3B is a kinesin motor protein that is also involved in the transport of GLUT4. RAB-4b is activated due to insulin stimulation, which is then associated with KIF3B. Therefore, it is indicated that the KIF3B motor protein can then attach to the microtubule, allowing GLUT4 exocytosis. ^{[15] [9]}

Another protein Rab-4B interacts with is STX4. STX4 is involved in the translocation of GLUT4, and this is facilitated when RAB4B is activated and can directly interact with STX4. ^{[16] [17]}

Rab4B has also been shown to interact with:

• CD2AP ^[18]
• RABEP1 ^[19]
• RAB11FIP1 ^[20]

Regulation

Rab-4B proteins have been found to be co-regulated with MHC Class II genes. ^[11]

Clinical significance

Rab4B is involved in cellular trafficking and has been revealed to play an important role in inflammation and insulin response, specifically through T cells. Obesity alters the composition of T cells in adipose tissue, which can cause the levels of Rab4B to be reduced, further leading to insulin resistance and dysfunctional adipose tissue. ^[21]

References

1. GRCh38: Ensembl release 89: ENSG00000167578 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000053291 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "UniProt". www.uniprot.org. Retrieved 2024-03-07.
6. "RAB4B RAB4B, member RAS oncogene family [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-03-07.
7. "Gene symbol report | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2024-03-08.
8. Zerial M, McBride H (February 2001). "Rab proteins as membrane organizers". Nature Reviews. Molecular Cell Biology. 2 (2): 107–117. doi:10.1038/35052055. PMID   11252952.
9. Jordens I, Marsman M, Kuijl C, Neefjes J (December 2005). "Rab proteins, connecting transport and vesicle fusion". Traffic. 6 (12): 1070–1077. doi:10.1111/j.1600-0854.2005.00336.x. PMID   16262719.
10. Kaddai V, Gonzalez T, Keslair F, Grémeaux T, Bonnafous S, Gugenheim J, et al. (April 2009). "Rab4b is a small GTPase involved in the control of the glucose transporter GLUT4 localization in adipocyte". PLOS ONE. 4 (4) e5257. Bibcode:2009PLoSO...4.5257K. doi: 10.1371/journal.pone.0005257 . PMC   2707114 . PMID   19590752.
11. Krawczyk M, Leimgruber E, Seguín-Estévez Q, Dunand-Sauthier I, Barras E, Reith W (January 2007). "Expression of RAB4B, a protein governing endocytic recycling, is co-regulated with MHC class II genes". Nucleic Acids Research. 35 (2): 595–605. doi:10.1093/nar/gkl980. PMC   1802633 . PMID   17175541.
12. Mohrmann K, Gerez L, Oorschot V, Klumperman J, van der Sluijs P (August 2002). "Rab4 function in membrane recycling from early endosomes depends on a membrane to cytoplasm cycle". The Journal of Biological Chemistry. 277 (35): 32029–32035. doi: 10.1074/jbc.M203064200 . PMID   12036958.
13. Hou L, Cai MJ, Liu W, Song Q, Zhao XF (November 2012). "Small GTPase Rab4b participates in the gene transcription of 20-hydroxyecdysone and insulin pathways to regulate glycogen level and metamorphosis". Developmental Biology. 371 (1): 13–22. doi: 10.1016/j.ydbio.2012.06.015 . PMID   22824427.
14. Perrin L, Lacas-Gervais S, Gilleron J, Ceppo F, Prodon F, Benmerah A, et al. (November 2013). "Rab4b controls an early endosome sorting event by interacting with the γ-subunit of the clathrin adaptor complex 1". Journal of Cell Science. 126 (Pt 21): 4950–62. doi:10.1242/jcs.130575. PMID   24006255.
15. Imamura T, Huang J, Usui I, Satoh H, Bever J, Olefsky JM (July 2003). "Insulin-induced GLUT4 translocation involves protein kinase C-lambda-mediated functional coupling between Rab4 and the motor protein kinesin". Molecular and Cellular Biology. 23 (14): 4892–4900. doi:10.1128/MCB.23.14.4892-4900.2003. PMC   162221 . PMID   12832475.
16. Li L, Omata W, Kojima I, Shibata H (February 2001). "Direct interaction of Rab4 with syntaxin 4". The Journal of Biological Chemistry. 276 (7): 5265–5273. doi: 10.1074/jbc.m003883200 . PMID   11063739.
17. Hutagalung AH, Novick PJ (January 2011). "Role of Rab GTPases in membrane traffic and cell physiology". Physiological Reviews. 91 (1): 119–149. doi:10.1152/physrev.00059.2009. PMC   3710122 . PMID   21248164.
18. Cormont M, Metón I, Mari M, Monzo P, Keslair F, Gaskin C, et al. (February 2003). "CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl". Traffic. 4 (2): 97–112. doi:10.1034/j.1600-0854.2003.40205.x. PMID   12559036.
19. Vitale G, Rybin V, Christoforidis S, Thornqvist P, McCaffrey M, Stenmark H, et al. (April 1998). "Distinct Rab-binding domains mediate the interaction of Rabaptin-5 with GTP-bound Rab4 and Rab5". The EMBO Journal. 17 (7): 1941–1951. doi:10.1093/emboj/17.7.1941. PMC   1170540 . PMID   9524117.
20. Lindsay AJ, Hendrick AG, Cantalupo G, Senic-Matuglia F, Goud B, Bucci C, et al. (April 2002). "Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein". The Journal of Biological Chemistry. 277 (14): 12190–12199. doi: 10.1074/jbc.m108665200 . PMID   11786538.
21. Gilleron J, Bouget G, Ivanov S, Meziat C, Ceppo F, Vergoni B, et al. (December 2018). "Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance". Cell Reports. 25 (12): 3329–3341.e5. doi:10.1016/j.celrep.2018.11.083. PMID   30566860.