KRAS (G12C), Isoform A, His-Tag, GppNHp-Loaded Recombinant

• Background:

  RAS is a group of small GTPase proteins encoded by 3 genes (HRAS, NRAS, and KRAS), which play critical roles in regulating cell proliferation. KRAS mutations are responsible for more than 30% of human cancers. The G12C mutation favors the activated (GTP-bound) state of KRAS, amplifying signaling pathways that lead to oncogenesis. Recent studies have led to the discovery of a small molecule called AMG510 (Amgen) that locks KRAS conformation in the GDP-bound (inactive) state, thereby blocking KRAS (G12C) -mediated signaling pathway.The KRAS (Kirsten rat sarcoma virus) gene is subject to alternative splicing, resulting in two isoforms: KRAS-A and KRAS-B. These isoforms differ by amino acids 151,153,165, and 166 and within the hypervariable region (amino acids 167-189) . KRAS-B contains a long polybasic stretch, while KRAS-A has a shorter polybasic region with a palmitoylation site. These differences confer distinct biological characteristics to the two isoforms. When studying a mutant of KRAS, it is important to know which isoform is being studied to make sure that the correct wild-type isoform is used for comparison. The identification of new strategies targeting KRAS G12C will bring large benefits in cancer therapy.

• Description:

  Recombinant human KRAS (GTPase), isoform a, encompassing amino acids 2-186. In this construct the N-terminal end of the protein contains a His-tag (6xHis) followed by an optimal TEV protease target sequence (TEV: tobacco etch virus cysteine protease #50308) . The protein also contains the cancer-associated mutation G12C. The protein was affinity purified and loaded with GppNHp, a non-hydrolyzable GTP analog. Unbound GppNHp was removed by spin column.

• UniProt:

  P01116

• Tag:

  N-terminal His-tag

• Applications:

  Useful for KRAS-RAF (rapidly accelerated fibrosarcoma) binding studies or inhibitor assays.

• Purity:

  ≥ 90%

• Shipping Conditions:

  -80°C

• Storage Conditions:

  At least 6 months at -80°C.

• Calculated Molecular Weight:

  23 kDa

• Formulation:

  20 mM HEPES, pH 7.4,150 mM NaCl, and 1 mM DTT.