RAS Proteins

Ras is a family of related proteins which is expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells (cellular signal transduction).

The 3 Ras genes in humans (HRas, KRas, and NRas) are the most common oncogenes in human cancer.

High occurrences of KRAS mutations in some types of cancers make KRAS one of the most important targets in oncology for drug development.  The five most frequent KRAS mutations are G12C, G12D, G12V, G13D, and Q61H. For this reason, Ras inhibitors are being studied as a treatment for cancer and other diseases with Ras overexpression.

Amid Biosciences offers most comprehensive set of recombinant biotinylated and non-biotinylated forms of KRAS proteins to advance drug discovery and medical research. Loading of the KRAS proteins with nucleotides or nucleotides' analogs can be performed if requested as a custom service.

Available biotinylated and non-biotinylated KRAS proteins: KRAS ("wild type"), KRAS G12C, KRAS G12D, KRAS G12R, KRAS G12V, KRAS G13D, KRAS Q61H, and KRAS Y96D (Table 1).

In addition, Amid Biosciences offers biomolecules (Raf1-RBD, SOS1, and SPH2)) involved in regulation of KRAS proteins (Table 1), RasA, RasB, Rheb proteins with sequence homology to Ras proteins, and  MEK1 protein which is a key player of Ras/MAP kinase signal transduction pathway. 

The Raf1 RBD protein binds specifically to GTP-bound Ras proteins. Ras proteins, like other small GTPases, regulate molecular events by cycling between an inactive GDP-bound form and an active GTP-bound form. In its active (GTP-bound) state, Ras binds specifically to the Ras-binding domain (RBD) of Raf1 to control downstream signaling cascades. 

The SOS1 (guanine nucleotide exchange factor) binds and activates GDP-bound RAS family proteins at its catalytic binding site and in this way promotes exchange of GDP for GTP. SOS1 plays a pivotal role in regulating receptor-ligand induced Ras activity. 

The SHP2 is tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf1 and activate downstream proliferative Ras/ERK/MAPK signalling.

The RAS-like oncoproteins A and B (RALA and RALB) are small G proteins which are critical downstream of effectors of RAS, along with RAF and PI3K.

The Rheb protein shares about 30–40% sequence identity with members of the Ras/Rap subfamily of small GTPases.

MEK1 and MEK2 proteins are substrates of RAF kinases.

Table 1. List of Ras and Ras-related Proteins.