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K-ras 2 proto-oncogene protein (GTPase KRas, K-Ras 2, Ki-Ras, c-K-ras, c-Ki-ras, KRAS, KRAS2, RASK2)

Function: - Ras proteins bind GDP/GTP & possess intrinsic GTPase activity - interacts with PHLPP (putative) - alternates between an inactive form bound to GDP & an active form bound to GTP - activated by a guanine nucleotide-exchange factor (GEF) & inactivated by a GTPase-activating protein (GAP) - p21ras binds to & activates raf1 protein probably in association with other proteins; raf1 activates MEK which in turn activates MAP kinases Structure: belongs to the small GTPase superfamily. Ras family Compartment: cell membrane, lipid-anchor, cytoplasmic side Alternative splicing: named isoforms=2 isoforms 2A & 2B differ in the C-terminal region encoded by two alternative exons (IVA & IVB) variant in position: 153:D->V (in CFC syndrome) Pathology: - defects in KRAS are a cause of a) acute myelogenous leukemia b) juvenile myelomonocytic leukemia c) Noonan syndrome 3 d) cardiofaciocutaneous syndrome e) KRAS mutations are involved in cancer development, colorectal carcinoma - KRAS-dependent tumor cells are dependent upon activity of STK33 [5]

Related

K-ras 2 proto-oncogene

Specific

K-ras 2A proto-oncogene protein K-ras 2B proto-oncogene protein

General

K-ras proto-oncogene protein (Kirsten ras)

Properties

SIZE: entity length = 189 aa MW = 22 kD COMPARTMENT: cytoplasm MOTIF: GTP-binding site SITE: 10-17 Effector region {32-40} GTP-binding site SITE: 57-61 GTP-binding site SITE: 116-119 Hypervariable region {166-185} MOTIF: cysteine residue {C180} MODIFICATION: palmitate COMPARTMENT: membrane CaaX motif SITE: C-TERMINUS QUALITIES: AAX-TRUNCATED CARBOXYMETHYLATED EFFECTOR-BOUND: farnesyl BOUND-VIA: cysteine residue

Database Correlations

OMIM correlations MORBIDMAP 190070 UniProt P01116 Pfam PF00071

References

  1. UniProt :accession P01116
  2. Atlas of genetics & cytogenetics in oncology & Haematology http://atlasgeneticsoncology.org/genes/KRASID91.html
  3. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=KRAS
  4. SHMPD; Note: The Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=KRAS
  5. Scholl C et al Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell 2009 May 29; 137:821 PMID: 19490892