RAB2B

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

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

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.

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

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