.doi.org/10.20517/cdr.2019.Figure 1. Amino acid sequences of RAS isoforms. The sequences of your RAS isoforms are compared and non-identical regions are marked by dashed rectangles. Amino acids 1-166 constitute the catalytic domain and amino acids 167-188/189 represent the hypervariable area. The amino acids are coloured depending on their physico-chemical properties. Hydrophobic (black), polar/neutral (green), acidic (red) und basic (blue)signal transduction pathways to regulate cell development, differentiation, and apoptosis[1]. Because of their protooncogenic character, RAS proteins are a popular target in the field of cancer research[2]. Essentially the most prominent members on the RAS family members will be the isoforms N-RAS, H-RAS, K-RAS 4A and K-RAS 4B. These proteins emerge from proto-oncogenes, as their point-mutations are regularly present in distinct types of cancer[3]. The amino acid sequence of all 4 isoforms is shown in Figure 1. The first 166 amino acids constitute the catalytic G-domain and share a sequence identity of 89 . The subsequent area spanning residues 167 to 188 and 189, respectively, differ amongst the isoforms. Hence, this C-terminal domain of RAS proteins is denoted as the hypervariable area. K-RAS 4A and 4B represent two splicing variants of the exon 4 from the K-RAS pre-mRNA and all four isoforms possess the C-terminal CaaX-Box. The cysteine at position 185 or 186 respectively is followed by two aliphatic amino acids and it is actually this cysteine that plays a vital part within the post-translational processing of RAS. All RAS isoforms are farnesylated to allow their anchoring for the membrane. Furthermore, K-RAS 4A is often palmitoylated at cysteine 180, N-RAS at cysteine 181, and H-RAS at cysteine 181 and 184. This extra palmitoylation increases the hydrophobicity with the protein. In contrast to this, K-RAS 4B isn’t palmitoylated but includes a poly lysine stretch (K175-K180) inside the hypervariable region alternatively. This positively charged sequence facilitates a much more transient anchorage for the negatively charged plasma membrane. RAS proteins function as binary molecular switches in signal transduction. They exist in an active GTPbound “ON”-state and an inactive GDP-bound “OFF”-state[4]. Within the active state, the G-protein is capable to bind to diverse effector proteins and transfer the signal. The intrinsic GTPase property enables the hydrolysis of GTP to GDP and hence the transition from the active to the inactive state. For the reactivation of RAS, the GDP nucleotide has to dissociate and the GTP nucleotide, that is present in a 10-fold excess, has to be incorporated. The intrinsic GDP-dissociation rate is 10-5 s-1[5] and hence as well low to become biologically substantial.Complement C3/C3a Protein Storage & Stability This price is enhanced 104-fold by guanine nucleotide exchange variables (GEFs)[6].NKp46/NCR1 Protein Purity & Documentation These GEFs are constructive regulators with the RAS activity.PMID:36014399 Hitherto, the protein encoded by the cell division cycle gene 25 (Cdc25) along with the son of sevenless (SOS) will be the greatest understood GEFs for RAS. GTPase activating proteins (GAPs)RAS – function and structureM chen et al . Cancer Drug Resist 2019;two:813-26 I http://dx.doi.org/10.20517/cdr.2019.PageFigure two. Crystal structure of K-RAS 4B GDP in ribbon representation (4EPY). The -helices (1-5), -sheets (1-6), the magnesiumion (Mg2+), plus the GDP nucleotide are labeled in black. The loops and switch regions are color-coded as follows: P-loop (red); switch I SW-I (green); G3-loop (blue); switch II – SW-II (yellow); G4-loop (magenta); G5-loop (orange)funct.