Introduction

Rab protein is a member of monomeric G-protein, which regulates numerous essential process in the cell. Rab proteins were usually bound with GTP binding sites to perform various functions in biology molecules. According to the functional role in membrane trafficking and cell physiology, Rab proteins could be classified into four classes, they are Rab GDP-dissociation inhibitor (GDI) activity, Rab geranylgeranyltransferase activity (GGT), Rab GTPase binding, Rab guanyl-nucleotide exchange factor activity. Fig. 1 shows the process of Rab cycle including all the molecular functions. Rab GGT plays the role as an enzyme in Rab system to transfer the geranylgeranyl and deliver the Rab to its target membrane. GDI activity prevents the association of GTP binding in Rab proteins system, so that keeps the Rab proteins in inactive state. Rab GEF activity stimulates the exchange of GDP to GTP binding sites to activate the Rab. Under normal condition, the priority of GTP is higher than GDP, then Rab GEF activity is activated to replace GDP by GTP. A GTPase binding aims to interact Rab with the binding sites and molecules and thereby convert the Rab back to its inactive state. The Rab then interacts with GTPase activating protein (GAP) and removed from the membrane via GDI.

Numerous types of Rab proteins now identified in human and several studies demonstrated that a functional loss of Rab proteins at each of the membrane trafficking steps had been implicated in many diseases i.e., choroideremia, intellectual disability, cancer, Parkinson’s disease. For instance, the modulation of Rab GGT molecular function has been related to Hermansky-Pudlak syndrome. The Rab GGT also used to develop some drug targets related to bone diseases, such as osteoporosis. Mutations in the Rab3GAP, which is a human class of the GAP process lead to X-linked nonspecific mental retardation, Warburg Micro and Martsolf syndromes, diseases characterized by developmental abnormalities of the eye, nervous system, and genitalia. A Rab GEF has also been implicated in human disease. Thus classification of Rab protein is a crucial topic and there is a requirement to develop some computational techniques to identify them.

Method

We approached a precise model using 2D CNN and PSSM profiles to classify the Rabs molecular functions in membrane trafficking. The flowchart of the study included four subprocesses: data collection, feature set generation, CNN generation and model evaluation. We describe the details of the proposed approach as follows.

Dataset

All the dataset using in this web server are retrieved from UniProt and GeneOntoly. The detail of the dataset lists in the below table.

If you would like to build a model and evaluate our model, we provide the dataset as the below link.

Members

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