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KRAS (Kirsten rat sarcoma 2 viral oncogene homolog)

Identity

Other namesK-RAS (Kirsten rat sarcoma 2 viral oncogene homolog)
c-Ki-ras 2
HGNC (Hugo) KRAS
LocusID (NCBI) 3845
Location 12p12.1
Location_base_pair Starts at 25357723 and ends at 25403865 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note more on the RAS family is available as a deep insight

DNA/RNA

 
  K-ras splicing variants alternative splicing of K-ras precursor mRNA leads to the two transcripts which differ by the ex- or inclusion of Exon 4a; Exons that encode protein are shown as black boxes, untranslated exons as white boxes; the upstream untranslated exon is indicated as Exon -1
Description consists of six exons, spread over 35kb of genomic DNA.
Transcription alternative RNA splicing reveals two different transcripts of 5.5 and 3.8kb (see Fig); if Exon 4a is skipped exon 4b is directly joined to exon 3; in 98% of the transcripts exon 4a is spliced out and only exon 4b is available for translation into protein.
Pseudogene c-Ki-ras 1, inactivated, processed pseudogene which is located on Chromosome 6

Protein

Description regular RAS protein - characterized in the RAS family page.
Expression ubiquitously expressed
Localisation anchored to the inner surface of the plasma membrane
Function analogously to other GTP-binding proteins (such as Translation Elongation Factor EFTu or signal transducing G-Proteins) RAS proteins are involved in signal transduction pathways
Homology ras gene family is part of the ras superfamily including the mammalian RAS, RAL, RAC, RHO, RAP, and RAB gene families and the yeast homologs like SEC4 and YPT1 genes; genes encode small monomeric proteins of low molecular mass (20-30 kDa) which share at least 30% homology to RAS proteins.

Implicated in

Entity tumor (frequency of K-RAS mutations); references in Full Bibliography
  
Entity pancreas (80-90%)
  
Entity colon and rectum (25-60%)
  
Entity lung (25-60%)
  
Entity prostate (0-25%)
  
Entity skin (0-25%)
  
Entity thyroid (0-60%)
  
Entity liver (10-25%)
  
Entity ovary (0-50%)
  
Entity endometrium (10-40%)
  
Entity kidney (0-50%)
  
Entity brain (0-15%)
  
Entity testis (seminoma) (10-45%)
  
Entity acute non lymphocytic leukemia and myelodysplasia (5-15%)
  
Entity urinary bladder (5%)
  
Entity head and neck (10%)
  
Entity breast (10%)
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004 rhabID5004 blad5001
bladID5001 colon5006 colonID5006 EmbryoRhabdomyoID5193 IrisHamartomaID5100
OvaryEpithTumID5230 rhab5004

External links

Nomenclature
HGNC (Hugo)KRAS   6407
Cards
AtlasKRASID91
Entrez_Gene (NCBI)KRAS  3845  Kirsten rat sarcoma viral oncogene homolog
GeneCards (Weizmann)KRAS
Ensembl (Hinxton)ENSG00000133703 [Gene_View]  chr12:25357723-25403865 [Contig_View]  KRAS [Vega]
ICGC DataPortalENSG00000133703
cBioPortalKRAS
AceView (NCBI)KRAS
Genatlas (Paris)KRAS
WikiGenes3845
SOURCE (Princeton)NM_004985 NM_033360
Genomic and cartography
GoldenPath (UCSC)KRAS  -  12p12.1   chr12:25357723-25403865 -  12p12.1   [Description]    (hg19-Feb_2009)
EnsemblKRAS - 12p12.1 [CytoView]
Mapping of homologs : NCBIKRAS [Mapview]
OMIM109800   114480   137215   163200   190070   211980   260350   609942   615278   
Gene and transcription
Genbank (Entrez)AA812162 AF493917 AI539465 AK292510 AW117295
RefSeq transcript (Entrez)NM_004985 NM_033360
RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NG_007524 NT_009714 NW_001838052 NW_004929383
Consensus coding sequences : CCDS (NCBI)KRAS
Cluster EST : UnigeneHs.505033 [ NCBI ]
CGAP (NCI)Hs.505033
Alternative Splicing : Fast-db (Paris)GSHG0007335
Alternative Splicing GalleryENSG00000133703
Gene ExpressionKRAS [ NCBI-GEO ]     KRAS [ SEEK ]   KRAS [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP01116 (Uniprot)
NextProtP01116  [Medical]
With graphics : InterProP01116
Splice isoforms : SwissVarP01116 (Swissvar)
Domaine pattern : Prosite (Expaxy)RAS (PS51421)   
Domains : Interpro (EBI)P-loop_NTPase [organisation]   Small_GTP-bd_dom [organisation]   Small_GTPase [organisation]   Small_GTPase_Ras [organisation]  
Related proteins : CluSTrP01116
Domain families : Pfam (Sanger)Ras (PF00071)   
Domain families : Pfam (NCBI)pfam00071   
Domain families : Smart (EMBL)RAS (SM00173)  
DMDM Disease mutations3845
Blocks (Seattle)P01116
PDB (SRS)1D8D    1D8E    1KZO    1KZP    3GFT    4DSN    4DSO    4EPR    4EPT    4EPV    4EPW    4EPX    4EPY    4L8G    4LPK    4LRW    4LUC    4LV6    4LYF    4LYH    4LYJ    4M1O    4M1S    4M1T    4M1W    4M1Y    4M21    4M22   
PDB (PDBSum)1D8D    1D8E    1KZO    1KZP    3GFT    4DSN    4DSO    4EPR    4EPT    4EPV    4EPW    4EPX    4EPY    4L8G    4LPK    4LRW    4LUC    4LV6    4LYF    4LYH    4LYJ    4M1O    4M1S    4M1T    4M1W    4M1Y    4M21    4M22   
PDB (IMB)1D8D    1D8E    1KZO    1KZP    3GFT    4DSN    4DSO    4EPR    4EPT    4EPV    4EPW    4EPX    4EPY    4L8G    4LPK    4LRW    4LUC    4LV6    4LYF    4LYH    4LYJ    4M1O    4M1S    4M1T    4M1W    4M1Y    4M21    4M22   
PDB (RSDB)1D8D    1D8E    1KZO    1KZP    3GFT    4DSN    4DSO    4EPR    4EPT    4EPV    4EPW    4EPX    4EPY    4L8G    4LPK    4LRW    4LUC    4LV6    4LYF    4LYH    4LYJ    4M1O    4M1S    4M1T    4M1W    4M1Y    4M21    4M22   
Human Protein AtlasENSG00000133703 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP01116
HPRD01817
IPIIPI00423568   IPI00423570   IPI01026223   IPI01026118   
Protein Interaction databases
DIP (DOE-UCLA)P01116
IntAct (EBI)P01116
FunCoupENSG00000133703
BioGRIDKRAS
InParanoidP01116
Interologous Interaction database P01116
IntegromeDBKRAS
STRING (EMBL)KRAS
Ontologies - Pathways
Ontology : AmiGOMAPK cascade  activation of MAPKK activity  positive regulation of protein phosphorylation  protein binding  GTP binding  mitochondrion  plasma membrane  GTP catabolic process  epidermal growth factor receptor signaling pathway  small GTPase mediated signal transduction  Ras protein signal transduction  axon guidance  blood coagulation  positive regulation of cell proliferation  insulin receptor signaling pathway  visual learning  fibroblast growth factor receptor signaling pathway  positive regulation of gene expression  membrane  GMP binding  GDP binding  cytokine-mediated signaling pathway  actin cytoskeleton organization  LRR domain binding  regulation of synaptic transmission, GABAergic  protein complex binding  positive regulation of Rac protein signal transduction  social behavior  Fc-epsilon receptor signaling pathway  positive regulation of MAP kinase activity  negative regulation of neuron apoptotic process  innate immune response  membrane raft  neurotrophin TRK receptor signaling pathway  regulation of long-term neuronal synaptic plasticity  leukocyte migration  positive regulation of nitric-oxide synthase activity  positive regulation of NF-kappaB transcription factor activity  striated muscle cell differentiation  response to glucocorticoid  response to mineralocorticoid  
Ontology : EGO-EBIMAPK cascade  activation of MAPKK activity  positive regulation of protein phosphorylation  protein binding  GTP binding  mitochondrion  plasma membrane  GTP catabolic process  epidermal growth factor receptor signaling pathway  small GTPase mediated signal transduction  Ras protein signal transduction  axon guidance  blood coagulation  positive regulation of cell proliferation  insulin receptor signaling pathway  visual learning  fibroblast growth factor receptor signaling pathway  positive regulation of gene expression  membrane  GMP binding  GDP binding  cytokine-mediated signaling pathway  actin cytoskeleton organization  LRR domain binding  regulation of synaptic transmission, GABAergic  protein complex binding  positive regulation of Rac protein signal transduction  social behavior  Fc-epsilon receptor signaling pathway  positive regulation of MAP kinase activity  negative regulation of neuron apoptotic process  innate immune response  membrane raft  neurotrophin TRK receptor signaling pathway  regulation of long-term neuronal synaptic plasticity  leukocyte migration  positive regulation of nitric-oxide synthase activity  positive regulation of NF-kappaB transcription factor activity  striated muscle cell differentiation  response to glucocorticoid  response to mineralocorticoid  
Pathways : BIOCARTATelomeres, Telomerase, Cellular Aging, and Immortality [Genes]   
Pathways : KEGGMAPK signaling pathway    ErbB signaling pathway    Ras signaling pathway    Rap1 signaling pathway    Chemokine signaling pathway    FoxO signaling pathway    PI3K-Akt signaling pathway    Dorso-ventral axis formation    Axon guidance    VEGF signaling pathway    Tight junction    Gap junction    Natural killer cell mediated cytotoxicity    T cell receptor signaling pathway    B cell receptor signaling pathway    Fc epsilon RI signaling pathway    Long-term potentiation    Neurotrophin signaling pathway    Cholinergic synapse    Serotonergic synapse    Long-term depression    Regulation of actin cytoskeleton    Insulin signaling pathway    GnRH signaling pathway    Progesterone-mediated oocyte maturation    Estrogen signaling pathway    Melanogenesis    Prolactin signaling pathway    Thyroid hormone signaling pathway    Aldosterone-regulated sodium reabsorption    Alcoholism    Hepatitis C    Hepatitis B    HTLV-I infection    Pathways in cancer    Viral carcinogenesis    Proteoglycans in cancer    MicroRNAs in cancer    Colorectal cancer    Renal cell carcinoma    Pancreatic cancer    Endometrial cancer    Glioma    Prostate cancer    Thyroid cancer    Melanoma    Bladder cancer    Chronic myeloid leukemia    Acute myeloid leukemia    Non-small cell lung cancer   
Protein Interaction DatabaseKRAS
Wikipedia pathwaysKRAS
Gene fusion - rearrangments
Rearrangement : COSMICUBE2L3 [22q11.21]  -  KRAS [12p12.1]  
  [COSF1298] [COSF1299] 
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)KRAS
snp3D : Map Gene to Disease3845
SNP (GeneSNP Utah)KRAS
SNP : HGBaseKRAS
Genetic variants : HAPMAPKRAS
Exome VariantKRAS
1000_GenomesKRAS 
ICGC programENSG00000133703 
Cancer Gene: CensusKRAS 
Somatic Mutations in Cancer : COSMICKRAS 
CONAN: Copy Number AnalysisKRAS 
Mutations and Diseases : HGMDKRAS
Mutations and Diseases : intOGenKRAS
Genomic VariantsKRAS  KRAS [DGVbeta]
dbVarKRAS
ClinVarKRAS
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM109800    114480    137215    163200    190070    211980    260350    609942    615278   
MedgenKRAS
GENETestsKRAS
Disease Genetic AssociationKRAS
Huge Navigator KRAS [HugePedia]  KRAS [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneKRAS
Homology/Alignments : Family Browser (UCSC)KRAS
Phylogenetic Trees/Animal Genes : TreeFamKRAS
Chemical/Protein Interactions : CTD3845
Chemical/Pharm GKB GenePA30196
Drug Sensitivity KRAS
Clinical trialKRAS
Cancer Resource (Charite)ENSG00000133703
Other databases
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=KRAS
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineKRAS
iHOPKRAS
OncoSearchKRAS

Bibliography

Human cancer and cellular oncogenes.
Nishimura S, Sekiya T
The Biochemical journal. 1987 ; 243 (2) : 313-327.
PMID 3307760
 
ras oncogenes in human cancer: a review.
Bos JL
Cancer research. 1989 ; 49 (17) : 4682-4689.
PMID 2547513
 
ras oncogenes: their role in neoplasia.
Barbacid M
European journal of clinical investigation. 1990 ; 20 (3) : 225-235.
PMID 2114981
 
ras activation in experimental carcinogenesis.
Mangues R, Pellicer A
Seminars in cancer biology. 1992 ; 3 (4) : 229-239.
PMID 1421167
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written02-1999Franz Watzinger and Thomas Lion

Citation

This paper should be referenced as such :
Watzinger, F ; Lion, T
KRAS (Kirsten rat sarcoma viral oncogene homolog)
Atlas Genet Cytogenet Oncol Haematol. 1999;3(2):66-67.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/KRASID91.html

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indexed on : Tue Aug 26 15:29:30 CEST 2014

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