RASEF

RASEF belongs to the small GTPase family, which means that it's able to hydrolyse a molecule of GTP; known for its unusual conformation. In the small GTPase family it is classified in the RAS domain, a special group of oncogenes and oncoproteins that take part in the synthesis of molecules related to cell reproduction.^[7]

A feature of RASEF is its N-terminal EF-hand motif and C-terminal Rab-homology domain, that enables it to bind calcium.^[7] Lately, RASEF has been studied for its role as an oncoprotein. Investigating which mutations affect it and how we could inhibit them could allow us to fight cancers that have an elevated mortality rate, such as lung cancer.^[7]

When studying cancer's molecular biology we can identify two types of genes that intervene in its development:

• Tumor suppressor genes: Inhibit tumor formation.
• Oncogenes: Stimulate cell proliferation. It is in this group where members of the RAS family are found.

Oncogenes generally code for growth factors and their receptors, enzymes related to transduction signal or for DNA transcription factors. When those genes suffer some kind of mutation or translocation, they can change their conformation and cause a catalytic activity in cell reproduction that is normally inactivated, which causes abnormal cell proliferation. This could provoke a malignant tumor if combined with a separate mutation in a protein's RAS group.^[8]

RASEF or Rab 45 is classified in the Ras superfamily, which includes small (20kDa) guanosine triphosphatases (GTPases). The basic members of this group of proteins are Ras oncogenes. It's divided into five major families (Ras, Rho, Arf/Sar, Ran and Rab).^[9] RASEF is included in the Rab family (the largest family), which is responsible for vesicular traffic of proteins between organelles via endocytotic and secretory pathways. Their function is to make budding from the donor compartment, transport, vesicle fusion and cargo release easier.^[10]

RASEF is a 740 amino acids^[11] long protein which contains 3 distinct regions: 2 EF hand domains (which in turn contain 2 Calcium bindings and 3 nucleotide bindings -assumed by similarity with other proteins, without direct evidence-), a Coiled Coil region and a C-terminal Rab-homology domain.^[7]

Sequence found in RASEF protein that contains 35 amino acids (36 in the second one). The two EF hand domains are consecutively located at the “beginning” of the protein. Its name “N-terminal” indicates an amino group (characteristic of this group of biomolecules, as well as the C- terminal ending). The first one goes from the 8th amino acid to the 42nd, and the other to the 42nd to the 77th.^[9] “EF hand” refers to the shape of this domain (similarity with the right hand's morphology). Ca+2 ions are responsible for this structure, which by binding metals join two alpha helixes.^[12]

Structural motif in proteins: from two to seven alpha helixes entwined. Each one of these helixes is a repeated 7 amino acid sequence (HPPHCPC), where H refers to hydrophobic amino acids.^[13] The position of hydrophobic remains (alpha helix exterior) causes their amphipathic behaviour.^{[citation needed]} The bond between different chains, produced in cytoplasm (aqueous region), is extremely tight, as Van der Waals forces appear between the hydrophobic radicals (H), surrounded by the hydrophilic amino acids (amphipathic molecule). This bond is known as the “Knobs into holes packing”.^[14] Coiled coil motif, located in the intermediate region of the protein, is responsible for self-interaction.^[15]

Located at the end of the protein (opposite to N-terminal domain), it's a carboxyl group (COOH). In this region, there are guanine nucleotide bonds to tri-phosphates and di-phosphates. The variability of this domain is responsible for the high appearance of elements needed in the joints between proteins and their targets in the membrane.^[16] Both the C-Terminal Rab-homology domain and the intermediate region of the protein are responsible for the intracellular location of the protein (perinuclear region).^{[citation needed]}