KRAS

4WA7, 1D8D, 1D8E, 3GFT, 4DSN, 4DSO, 4EPR, 4EPT, 4EPV, 4EPW, 4EPX, 4EPY, 4L8G, 4LDJ, 4LPK, 4LRW, 4LUC, 4LV6, 4LYF, 4LYH, 4LYJ, 4M1O, 4M1S, 4M1T, 4M1W, 4M1Y, 4M21, 4M22, 4NMM, 4OBE, 4PZY, 4PZZ, 4Q01, 4Q02, 4Q03, 4QL3, 4TQ9, 4TQA, 4DST, 4DSU, 5F2E,%%s2MSC, 2MSD, 2MSE384516653ENSG00000133703ENSMUSG00000030265P01116P32883NM_004985NM_033360NM_001369786NM_001369787NM_021284NP_004976NP_203524NP_001356715NP_001356716NP_004976.2NP_067259KRAS ( K-ras or Ki-ras) is a gene that acts as an on/off switch in cell signalling. When it functions normally, it controls cell proliferation. When it is mutated, negative signalling is disrupted. Thus, cells can continuously proliferate, and often develop into cancer.121p: STRUKTUR UND GUANOSINTRIPHOSPHAT-HYDROLYSEMECHANISMUS DES C-TERMINAL VERKUERZTEN MENSCHLICHEN KREBSPROTEINS P21-H-RAS1aa9: HUMAN C-HA-RAS(1-171)(DOT)GDP, NMR, MINIMIZED AVERAGE STRUCTURE1agp: THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLY-12 MUTANT OF P21-H-RAS1bkd: COMPLEX OF HUMAN H-RAS WITH HUMAN SOS-11clu: H-RAS COMPLEXED WITH DIAMINOBENZOPHENONE-BETA,GAMMA-IMIDO-GTP1crp: THE SOLUTION STRUCTURE AND DYNAMICS OF RAS P21. GDP DETERMINED BY HETERONUCLEAR THREE AND FOUR DIMENSIONAL NMR SPECTROSCOPY1crq: THE SOLUTION STRUCTURE AND DYNAMICS OF RAS P21. GDP DETERMINED BY HETERONUCLEAR THREE AND FOUR DIMENSIONAL NMR SPECTROSCOPY1crr: THE SOLUTION STRUCTURE AND DYNAMICS OF RAS P21. GDP DETERMINED BY HETERONUCLEAR THREE AND FOUR DIMENSIONAL NMR SPECTROSCOPY1ctq: STRUCTURE OF P21RAS IN COMPLEX WITH GPPNHP AT 100 K1gnp: X-RAY CRYSTAL STRUCTURE ANALYSIS OF THE CATALYTIC DOMAIN OF THE ONCOGENE PRODUCT P21H-RAS COMPLEXED WITH CAGED GTP AND MANT DGPPNHP1gnq: X-RAY CRYSTAL STRUCTURE ANALYSIS OF THE CATALYTIC DOMAIN OF THE ONCOGENE PRODUCT P21H-RAS COMPLEXED WITH CAGED GTP AND MANT DGPPNHP1gnr: X-RAY CRYSTAL STRUCTURE ANALYSIS OF THE CATALYTIC DOMAIN OF THE ONCOGENE PRODUCT P21H-RAS COMPLEXED WITH CAGED GTP AND MANT DGPPNHP1he8: RAS G12V - PI 3-KINASE GAMMA COMPLEX1iaq: C-H-RAS P21 PROTEIN MUTANT WITH THR 35 REPLACED BY SER (T35S) COMPLEXED WITH GUANOSINE-5'- TRIPHOSPHATE1ioz: Crystal Structure of the C-HA-RAS Protein Prepared by the Cell-Free Synthesis1jah: H-RAS P21 PROTEIN MUTANT G12P, COMPLEXED WITH GUANOSINE-5'- TRIPHOSPHATE AND MAGNESIUM1jai: H-RAS P21 PROTEIN MUTANT G12P, COMPLEXED WITH GUANOSINE-5'- TRIPHOSPHATE AND MANGANESE1k8r: Crystal structure of Ras-Bry2RBD complex1lf0: Crystal Structure of RasA59G in the GTP-bound form1lf5: Crystal Structure of RasA59G in the GDP-bound Form1lfd: CRYSTAL STRUCTURE OF THE ACTIVE RAS PROTEIN COMPLEXED WITH THE RAS-INTERACTING DOMAIN OF RALGDS1nvu: Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS1nvv: Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS1nvw: Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS1nvx: Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS1p2s: H-Ras 166 in 50% 2,2,2 triflouroethanol1p2t: H-Ras 166 in Aqueous mother liquor, RT1p2u: H-Ras in 50% isopropanol1p2v: H-RAS 166 in 60 % 1,6 hexanediol1plj: CRYSTALLOGRAPHIC STUDIES ON P21H-RAS USING SYNCHROTRON LAUE METHOD: IMPROVEMENT OF CRYSTAL QUALITY AND MONITORING OF THE GTPASE REACTION AT DIFFERENT TIME POINTS1plk: CRYSTALLOGRAPHIC STUDIES ON P21H-RAS USING SYNCHROTRON LAUE METHOD: IMPROVEMENT OF CRYSTAL QUALITY AND MONITORING OF THE GTPASE REACTION AT DIFFERENT TIME POINTS1pll: CRYSTALLOGRAPHIC STUDIES ON P21H-RAS USING SYNCHROTRON LAUE METHOD: IMPROVEMENT OF CRYSTAL QUALITY AND MONITORING OF THE GTPASE REACTION AT DIFFERENT TIME POINTS1q21: CRYSTAL STRUCTURES AT 2.2 ANGSTROMS RESOLUTION OF THE CATALYTIC DOMAINS OF NORMAL RAS PROTEIN AND AN ONCOGENIC MUTANT COMPLEXED WITH GSP1qra: STRUCTURE OF P21RAS IN COMPLEX WITH GTP AT 100 K1rvd: H-RAS COMPLEXED WITH DIAMINOBENZOPHENONE-BETA,GAMMA-IMIDO-GTP1wq1: RAS-RASGAP COMPLEX1xcm: Crystal structure of the GppNHp-bound H-Ras G60A mutant1xd2: Crystal Structure of a ternary Ras:SOS:Ras*GDP complex1xj0: Crystal Structure of the GDP-bound form of the RasG60A mutant1zvq: Structure of the Q61G mutant of Ras in the GDP-bound form1zw6: Crystal Structure of the GTP-bound form of RasQ61G221p: THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES2c5l: STRUCTURE OF PLC EPSILON RAS ASSOCIATION DOMAIN WITH HRAS2ce2: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GDP2cl0: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GPPNHP2cl6: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH S-CAGED GTP2cl7: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GTP2clc: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GTP (2)2cld: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GDP (2)2evw: Crystal structure analysis of a fluorescent form of H-Ras p21 in complex with R-caged GTP2q21: CRYSTAL STRUCTURES AT 2.2 ANGSTROMS RESOLUTION OF THE CATALYTIC DOMAINS OF NORMAL RAS PROTEIN AND AN ONCOGENIC MUTANT COMPLEXED WITH GSP421p: THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES521p: THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES5p21: REFINED CRYSTAL STRUCTURE OF THE TRIPHOSPHATE CONFORMATION OF H-RAS P21 AT 1.35 ANGSTROMS RESOLUTION: IMPLICATIONS FOR THE MECHANISM OF GTP HYDROLYSIS621p: THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES6q21: MOLECULAR SWITCH FOR SIGNAL TRANSDUCTION: STRUCTURAL DIFFERENCES BETWEEN ACTIVE AND INACTIVE FORMS OF PROTOONCOGENIC RAS PROTEINS721p: THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES821p: THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLYCINE-12 MUTANT OF P21H-RAS KRAS ( K-ras or Ki-ras) is a gene that acts as an on/off switch in cell signalling. When it functions normally, it controls cell proliferation. When it is mutated, negative signalling is disrupted. Thus, cells can continuously proliferate, and often develop into cancer. It is called KRAS because it was first identified as an oncogene in Kirsten RAt Sarcoma virus. The viral oncogene was derived from cellular genome. Thus, KRAS gene in cellular genome is called a proto-oncogene. The gene product was first found as a p21 GTPase. Like other members of the ras subfamily, the KRAS protein is a GTPase and is an early player in many signal transduction pathways. KRAS is usually tethered to cell membranes because of the presence of an isoprene group on its C-terminus. There are two protein products of the KRAS gene in mammalian cells that result from the use of alternative exon 4 (exon 4A and 4B respectively): K-Ras4A and K-Ras4B, these proteins have different structure in their C-terminal region and use different mechanisms to localize to cellular membranes including the plasma membrane. KRAS acts as a molecular on/off switch, using protein dynamics. Once it is allosterically activated, it recruits and activates proteins necessary for the propagation of growth factors, as well as other cell signaling receptors like c-Raf and PI 3-kinase. KRAS upregulates the GLUT1 glucose transporter, thereby contributing to the Warburg effect in cancer cells. KRAS binds to GTP in its active state. It also possesses an intrinsic enzymatic activity which cleaves the terminal phosphate of the nucleotide, converting it to GDP. Upon conversion of GTP to GDP, KRAS is deactivated. The rate of conversion is usually slow, but can be increased dramatically by an accessory protein of the GTPase-activating protein (GAP) class, for example RasGAP. In turn, KRAS can bind to proteins of the Guanine Nucleotide Exchange Factor (GEF) class (such as SOS1), which forces the release of bound nucleotide (GDP). Subsequently, KRAS binds GTP present in the cytosol and the GEF is released from ras-GTP. Other members of the Ras family include: HRAS and NRAS. These proteins all are regulated in the same manner and appear to differ in their sites of action within the cell. This proto-oncogene is a Kirsten ras oncogene homolog from the mammalian ras gene family. A single amino acid substitution, and in particular a single nucleotide substitution, is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal cancer. Several germline KRAS mutations have been found to be associated with Noonan syndrome and cardio-facio-cutaneous syndrome. Somatic KRAS mutations are found at high rates in leukemias, colorectal cancer, pancreatic cancer and lung cancer. The impact of KRAS mutations is heavily dependent on the order of mutations. Primary KRAS mutations generally lead to a self-limiting hyperplastic or borderline lesion, but if they occur after a previous APC mutation it often progresses to cancer. KRAS mutations are more commonly observed in cecal cancers than colorectal cancers located in any other places from ascending colon to rectum.