RAB2B

Last updated
RAB2B
RAB2B.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases RAB2B , member RAS oncogene family, RAB protein-GTP binding protein- RAS protein
External IDs OMIM: 607466 MGI: 1923588 HomoloGene: 23789 GeneCards: RAB2B
Orthologs
SpeciesHumanMouse
Entrez

84932

76338

Ensembl

ENSG00000129472

ENSMUSG00000022159

UniProt

Q8WUD1

P59279

RefSeq (mRNA)

NM_001163380
NM_032846

NM_172601

RefSeq (protein)

NP_001156852
NP_116235

NP_766189

Location (UCSC) Chr 14: 21.46 – 21.48 Mb Chr 14: 52.5 – 52.52 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ras-related protein Rab-2B is a protein that in humans is encoded by the RAB2B gene.

Contents

RAB2B is required for protein transport from the endoplasmic reticulum to the Golgi complex. It belongs to the small GTPase superfamily, specifically to the RAB protein family. [5] Small GTPases are a type of hydrolase enzymes that can attach to a GTP to form a GDP. This process makes small GTPases active when bonded to a GTP and inactive when bonded to a GDP. Inside this small GTPase superfamily we can find the RAS subfamily. This family is divided into 5 groups: Ras, Rho, Ran, Rab and Arf GTPases. RAB2B’s main function is regulating vesicle transport and membrane fusion.

Structure

RAB2B is a human protein whose gene is located in the fourteenth chromosome. It has a core made of basic elements such as oxygen, carbon, nitrogen and phosphorus. Its secondary structure contains eight alpha helix and six beta strands. Moreover, it has attached a magnesium ion and a GDP. [6]

Mature RAB2B contains three post-translational modifications, a phosphoserine is found in the location 202 instead of a normal serine, and two lipidations can be found in locations 215-216. It has a motif domain between the amino acids 35 and 43.

Due to the alternative splicing, two isoforms of this same protein exist. Isoform 1 is the canonical sequence, meaning it is the most common one, having a molecular weight of 24,214 Da. [7] Isoform 2 consists just of 151 amino acids, having a mass of 16,667 Da.

Function

Small GTPases of the RAB superfamily are recognized as key players of the protein machinery involved in vesicular transport [8] and organelle dynamics in eukaryotic cells. RAB2B follows mainly exocytic pathways, from the endoplasmic reticulum to Golgi complex. RAB proteins are involved in docking and fusion of transport vesicles with their target membranes. These proteins associate with effector proteins (GARIL4 and GARIL5) to create complexes.

Representation of how RAB2B acts during an antiviral response and the elements it interacts with RAB2B in antiviral response.png
Representation of how RAB2B acts during an antiviral response and the elements it interacts with

In order to do its biological function, RAB2B has to switch from the GDP form to the GTP form, and this is possible thanks to the catalysation of GEF proteins, which are guanine exchange factors. On the other hand, when RAB2B are inactive in the cytosol, the GDP form is maintained due to the interaction with GDI proteins, which are GDP dissociation proteins. [9]

Studies have also shown that RAB2B affects the IFN antiviral response which is induced by cytosolic DNA. Because of this, RAB2B deficiency allows for vaccinia virus to replicate itself. After DNA stimulation, RAB2B attaches itself on the Golgi apparatus, along with stimulator of interferon genes (STING), the downstream signal mediator of cGAS. In order for RAB2B to adhere to the Golgi apparatus, RAB2B’s GTP-binding activity is required, as well as for the recruitment of GARIL5, so the RAB2B-GARIL5 complex can be formed. It is also shown that GARIL5 deficiency affects the IFN antiviral response, indicating that the entire RAB2B-GARIL5 complex regulates the cGAS-STING signalling axis, thus promoting IFN responses against cytosolic DNA (DNA viruses). [10]

RAB2B isoform knockdown affects the morphology of the Golgi complex in mammals, inducing its fragmentation. [11] Even though these RAB family proteins are highly homologous to each other (RAB2A and RAB2B have 85.8% amino acid identity), the knockdown of any of them (from RAB1A to RAB8A) causes Golgi complex to disperse through the cell's cytoplasm. Because of this, the RAB2B-GARIL5 complex stops functioning properly, affecting the IFN response [10] and enhancing the replication of many viruses, as seen previously.

Tissue distribution

The expression pattern of the human RAB2B gene reveals a transcript in kidney, prostate, lung, thymus, and colon, and a lower expression level in placenta, pancreas and skeletal muscle. Moreover, it is shown that the transcript is over-expressed in colon adenocarcinoma, as well as pancreatic cancer. [12] This observation entails that this protein could have a close relationship with colon tumours. [13]

Related Research Articles

GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a protein domain common to many GTPases.

Small GTPases, also known as small G-proteins, are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotrimeric G-proteins, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to form guanosine diphosphate (GDP). The best-known members are the Ras GTPases and hence they are sometimes called Ras subfamily GTPases.

The Coat Protein Complex II, or COPII, is a group of proteins that facilitate the formation of vesicles to transport proteins from the endoplasmic reticulum to the Golgi apparatus or endoplasmic-reticulum–Golgi intermediate compartment. This process is termed anterograde transport, in contrast to the retrograde transport associated with the COPI complex. COPII is assembled in two parts: first an inner layer of Sar1, Sec23, and Sec24 forms; then the inner coat is surrounded by an outer lattice of Sec13 and Sec31.

The Rab family of proteins is a member of the Ras superfamily of small G proteins. Approximately 70 types of Rabs have now been identified in humans. Rab proteins generally possess a GTPase fold, which consists of a six-stranded beta sheet which is flanked by five alpha helices. Rab GTPases regulate many steps of membrane trafficking, 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.

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

GTPase HRas, from "Harvey Rat sarcoma virus", also known as transforming protein p21 is an enzyme that in humans is encoded by the HRAS gene. The HRAS gene is located on the short (p) arm of chromosome 11 at position 15.5, from base pair 522,241 to base pair 525,549. HRas is a small G protein in the Ras subfamily of the Ras superfamily of small GTPases. Once bound to Guanosine triphosphate, H-Ras will activate a Raf kinase like c-Raf, the next step in the MAPK/ERK pathway.

<span class="mw-page-title-main">RAS p21 protein activator 1</span> Protein-coding gene in the species Homo sapiens

RAS p21 protein activator 1 or RasGAP, also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities:

<span class="mw-page-title-main">RAB7A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-7a is a protein that in humans is encoded by the RAB7A gene.

<span class="mw-page-title-main">RAB6A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-6A is a protein that in humans is encoded by the RAB6A gene located in the eleventh chromosome. Its main function is the regulation of protein transport from the Golgi complex to the endoplasmic reticulum and the exocytosis along with the microtubules.

<span class="mw-page-title-main">GDI1</span> Protein-coding gene in the species Homo sapiens

Rab GDP dissociation inhibitor alpha is a protein that in humans is encoded by the GDI1 gene.

<span class="mw-page-title-main">RAC2</span> Protein-coding gene in the species Homo sapiens

Rac2 is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RAC2.

<span class="mw-page-title-main">RAP2A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rap-2a is a protein that in humans is encoded by the RAP2A gene. RAP2A is a member of the Ras-related protein family.

<span class="mw-page-title-main">RAB1A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-1A is a protein that in humans is encoded by the RAB1A gene.

<span class="mw-page-title-main">RAB8A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-8A is a protein that in humans is encoded by the RAB8A gene.

<span class="mw-page-title-main">RAB1B</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-1B is a protein that in humans is encoded by the RAB1B gene.

<span class="mw-page-title-main">RAB2A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-2A is a protein that in humans is encoded by the RAB2A gene.

<span class="mw-page-title-main">RAB11B</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-11B is a protein that in humans is encoded by the RAB11B gene. Rab11b is reported as most abundantly expressed in brain, heart and testes.

<span class="mw-page-title-main">RAB33A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-33A is a protein that in humans is encoded by the RAB33A gene.

<span class="mw-page-title-main">RAB8B</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-8B is a protein that in humans is encoded by the RAB8B gene.

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

Ras-related GTP-binding protein B is a protein that in humans is encoded by the RRAGB gene.

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

Ras and EF-hand domain-containing protein also known as Ras-related protein Rab-45 is a protein that in humans is encoded by the RASEF gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000129472 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022159 - 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. ↑ "RAB2B - Ras-related protein Rab-2B - Homo sapiens (Human) - RAB2B gene & protein". www.uniprot.org. Retrieved 2019-10-18.
  6. ↑ "iCn3D: Web-based 3D Structure Viewer". www.ncbi.nlm.nih.gov. Retrieved 2019-10-26.
  7. ↑ "RAB2B (human)". www.phosphosite.org. Retrieved 2019-10-26.
  8. ↑ Martinez O, Goud B (August 1998). "Rab proteins". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1404 (1–2): 101–12. doi: 10.1016/S0167-4889(98)00050-0 . PMID   9714762.
  9. ↑ Martinez, Olivier; Goud, Bruno (1998-08-14). "Rab proteins". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1404 (1): 101–112. doi: 10.1016/S0167-4889(98)00050-0 . ISSN   0167-4889. PMID   9714762.
  10. 1 2 Takahama M, Fukuda M, Ohbayashi N, Kozaki T, Misawa T, Okamoto T, et al. (September 2017). "The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses". Cell Reports. 20 (12): 2944–2954. doi:10.1016/j.celrep.2017.08.085. PMC   5614515 . PMID   28930687.
  11. ↑ Aizawa M, Fukuda M (September 2015). "Small GTPase Rab2B and Its Specific Binding Protein Golgi-associated Rab2B Interactor-like 4 (GARI-L4) Regulate Golgi Morphology". The Journal of Biological Chemistry. 290 (36): 22250–61. doi: 10.1074/jbc.M115.669242 . PMC   4571976 . PMID   26209634.
  12. ↑ Jin J, Wu Y, Zhou D, Sun Q, Wang W (September 2018). "miR‑448 targets Rab2B and is pivotal in the suppression of pancreatic cancer". Oncology Reports. 40 (3): 1379–1389. doi:10.3892/or.2018.6562. PMC   6072403 . PMID   30015954.
  13. ↑ Ni X, Ma Y, Cheng H, Jiang M, Guo L, Ji C, et al. (2002). "Molecular cloning and characterization of a novel human Rab ( Rab2B) gene". Journal of Human Genetics. 47 (10): 548–51. doi: 10.1007/s100380200083 . PMID   12376746.
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