RAB4B

Last updated
RAB4B
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases RAB4B , member RAS oncogene family
External IDs OMIM: 612945 MGI: 105071 HomoloGene: 100632 GeneCards: RAB4B
Orthologs
SpeciesHumanMouse
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]

Contents

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. RAB exocytosis.png
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:

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]

Related Research Articles

Glucose transporter type 4 (GLUT4), also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the SLC2A4 gene. GLUT4 is the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle. The first evidence for this distinct glucose transport protein was provided by David James in 1988. The gene that encodes GLUT4 was cloned and mapped in 1989.

<span class="mw-page-title-main">RAB5A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-5A is a protein that in humans is encoded by the RAB5A gene.

<span class="mw-page-title-main">SNAP23</span> Protein-coding gene in the species Homo sapiens

Synaptosomal-associated protein 23 is a protein that in humans is encoded by the SNAP23 gene. Two alternative transcript variants encoding different protein isoforms have been described for this gene.

<span class="mw-page-title-main">RAB11A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-11A is a protein that in humans is encoded by the RAB11A gene.

<span class="mw-page-title-main">RAB4A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-4A is a protein that in humans is encoded by the RAB4A gene.

<span class="mw-page-title-main">STX4</span> Protein-coding gene in the species Homo sapiens

Syntaxin-4 is a protein that in humans is encoded by the STX4 gene.

<span class="mw-page-title-main">VAMP2</span> Protein-coding gene in the species Homo sapiens

Vesicle-associated membrane protein 2 (VAMP2) is a protein that in humans is encoded by the VAMP2 gene.

<span class="mw-page-title-main">PIKFYVE</span> Protein-coding gene in the species Homo sapiens

PIKfyve, a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene.

<span class="mw-page-title-main">RAB11FIP1</span> Protein-coding gene in the species Homo sapiens

Rab11 family-interacting protein 1 (Rab11-FIP1) also known as Rab-coupling protein is a protein that in humans is encoded by the RAB11FIP1 gene.

<span class="mw-page-title-main">TBC1D4</span> Protein-coding gene in the species Homo sapiens

AS160, which was originally known as TBC1 domain family member 4 (TBC1D4), is a Rab GTPase-activating protein that in humans is encoded by the TBC1D4 gene.

<span class="mw-page-title-main">NISCH</span> Protein-coding gene in the species Homo sapiens

Nischarin is a protein that in humans is encoded by the NISCH gene.

<span class="mw-page-title-main">RAB11FIP5</span> Protein-coding gene in the species Homo sapiens

Rab11 family-interacting protein 5 is a protein that in humans is encoded by the RAB11FIP5 gene.

<span class="mw-page-title-main">RABEP1</span> Protein-coding gene in the species Homo sapiens

Rab GTPase-binding effector protein 1 is an enzyme that in humans is encoded by the RABEP1 gene. It belongs to rabaptin protein family.

<span class="mw-page-title-main">KIF3B</span> Protein-coding gene in the species Homo sapiens

Kinesin-like protein KIF3B is a protein that in humans is encoded by the KIF3B gene. KIF3B is an N-type protein that complexes with two other kinesin proteins to form two-headed anterograde motors. First, KIF3B forms a heterodimer with KIF3A ; (KIF3A/3B), that is membrane-bound and has ATPase activity. Then KIFAP3 binds to the tail domain to form a heterotrimeric motor. This motor has a plus end-directed microtubule sliding activity that exhibits a velocity of ~0.3 μm/s a. There are 14 kinesin protein families in the kinesin superfamily and KIF3B is part of the Kinesin-2 family, of kinesins that can all form heterotrimeric complexes. Expression of the three motor subunits is ubiquitous. The KIG3A/3B/KAP3 motors can transport 90 to 160 nm in diameter organelles.

<span class="mw-page-title-main">RAB22A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-22A is a protein that in humans is encoded by the RAB22A gene.

<span class="mw-page-title-main">STXBP5</span> Protein-coding gene in the species Homo sapiens

Syntaxin-binding protein 5 is a protein that in humans is encoded by the STXBP5 gene. It is also known as tomosyn, after 友, "friend" in Japanese, for its role as a binding protein.

<span class="mw-page-title-main">GAPVD1</span> Protein-coding gene in the species Homo sapiens

GTPase activating protein and VPS9 domains 1, also known as GAPVD1, Gapex-5 and RME-6 is a protein which in humans is encoded by the GAPVD1 gene.

The EHD protein family is a relatively small group of proteins which have been shown to play a role in several physiological functions, the most notable being the regulation of endocytotic vesicles. This family is recognized by its highly conserved EH domain, a structural motif that has been shown to facilitate specificity and interaction between protein and ligand. The four mammalian EHD proteins that have been classified are: EHD1, EHD2, EHD3, and EHD4.

<span class="mw-page-title-main">Rabaptin</span>

Rabaptin is a key protein involved in regeneration of injured axons.

<span class="mw-page-title-main">TBC domain</span>

The TBC domain is an evolutionarily conserved protein domain found in all eukaryotes. It is approximately 180 to 200 amino acids long. The domain is named for its initial discovery in the proteins Tre-2, Bub2, and Cdc16.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000167578 – Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 1 2 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. 1 2 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.
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