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FLASH GENE
Symbol KRAS contributors: mct - updated : 21-05-2012
HGNC name v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
HGNC id 6407
Corresponding disease
CFC5 cardio-facio-cutaneous syndrome
NS3 Noonan syndrome 3
Location 12p12.1      Physical location : 25.358.179 - 25.403.854
Synonym name
  • oncogene KRAS2
  • cellular c-ki-ras2 protooncogene
  • v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog
  • PR310 c-K-ras oncogene
  • Kirsten rat sarcoma-2 viral (v-Ki-ras2) oncogene homolog
  • Synonym symbol(s) RASK2, KI-RAS, K-RAS2A, K-RAS4A, K-RAS4B, K-RAS2B, C-K-RAS, KRAS2, EVI80, KRAS1, RAS, NS
    DNA
    TYPE functioning gene
    STRUCTURE 45.68 kb     6 Exon(s)
    MAPPING cloned Y linked Y status confirmed
    Map pter - D12S363 - D12S301 - (D12S1085 , IAPP , KCNJ8 , RECQL , GYS2 , D12S1066 , LDHB ) - D12S849 - (D12S1027 , D12S310 ) - D12S863 - D12S1669 - D12S1452 - D12S205 - (D12S1168E , D12S1155E ) - D12S2048 - D12S1606 - D12S1057 - D12S1435 - KRAS - D12S1134E - D12S1313 - D12S1596 - D12S1034 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 5436 21 189 - 2008 18818716
  • also called variant a or K-RAS4A
  • including exon 4a
  • shares with HRAS and NRAS a post-translational modification that includes covalent attachment of a palmitoyl moiety
  • importance in tumorigenesis, retaining a critical role in tumor relapses, for example,by supporting the self-renewal capacity of tumor-initiating cells
  • 5 splicing 5312 21 188 - 2008 18818716
  • also called variant b or K-RAS4B
  • lacking exon 4a compared to variant a
  • having C-terminal hexa-lysine motif
  • this predominant variant b has a cds terminating in exon 4b
  • mutation associated to severe Noonan syndrome
  • limited to farnesylation or geranylgeranylation
  • its hypervariable region is responsible for its specific interactions with CALM1
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas    
     thyroid   highly
    Lymphoid/Immunelymph node   highly
    Nervousbrain    
    Reproductivefemale systemovary  highly
    Urinarykidney    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • terminating with a CAAX motif, clipped off by RCE1, an integral membrane endoprotease of the endoplasmic reticulum
  • HOMOLOGY
    interspecies ortholog to murine Kras
    ortholog to rattus Kras2
    Homologene
    FAMILY
  • GTP binding protein family
  • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,nucleus,nucleolus
    text
  • associated with the mitochondrial outer membrane
  • CALM1 colocalized with KRAS mainly at the plasma membrane
  • basic FUNCTION
  • GTPase, p21 Ras (signal transduction), involved in genetic instability and apoptosis
  • involved in the regulation of cell division as a result of its ability to relay external signals to the cell nucleus
  • not phosphorylated, it exhibits a remarkably decreased ability to stimulate proliferation in non-saturated serum conditions
  • modulates mitochondrial metabolism inbcolon cancer cells by inducing HIF1A and HIF2A target genes
  • in pancreatic ductal adenocarcinoma (PDAC), oncogenic KRAS plays a critical role in coordinating the shift in Gln metabolism to maintain tumour growth and survival
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    key regulator of the RAS-RAF-MEK-ERK pathway
    a component
  • pro-apoptotic pathway linking KRAS, RASSF1 and BAX that is specifically impaired in some human tumors
  • part of a novel regulatory network composed of RASSF5, the mitotic kinase Aurora A, the small GTPase KRAS, and the microtubule cytoskeleton
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • GTP
  • protein
  • with RAC1 and RHoA, bind to RAP1GDS1 in both active and inactive forms which requires the presence of poly-basic residues in the C-termini of the GTPases
  • galectin-3 interacts with activated KRAS through the hypervariable C-terminal region and stimulates KRAS activity triggering a RAS signal that attenuates ERK, but not PI3K
  • CALM1 binds to KRAS and KRAS phosphorylation inhibits its interaction with CALM1
  • interaction with HIF1A nd HIF2A (HIF1A and HIF2A work together to modulate cancer metabolism and regulate genes signature overlapping with oncogenic KRAS)
  • NFE2L2 interacting with KRAS and MYC (KRAS and MYC oncogenes can constitutively increase the transcription of NFE2L2 to elevate the basal activity of the antioxidant and cellular detoxification program)
  • regulates BRIP1 expression to induce dissociation of BRCA1 from chromatin, inhibit DNA repair, and promote senescence
  • KRAS stimulates BMP7 secretion and BMP signaling, leading to MAP3K7 activation and enhancement of Wnt-dependent transcription
  • novel interplay between KRAS and HRAS, with possible implications for colorectal carcinogenesis
  • critical role for the cell surface molecule CD44 in mediating cell proliferation downstream of oncogenic KRAS signaling
  • cell & other
    REGULATION
    Other CALM1 interaction and PKC phosphorylation is essential to regulate non-oncogenic and oncogenic KRAS activity and functionality
    phosphorylated in the presence of growth factors, or upon PKC stimulation and this phosphorylation is inhibited by CALM1 interaction
    ASSOCIATED DISORDERS
    corresponding disease(s) NS3 , CFC5
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in non small cell lung adenocarcinomas, in pancreatic cancer, in endometrial carcinoma (not in endometrial hyperplasia)and in thyroid cancer with poor prognosis
    tumoral somatic mutation      
    in MM and PPCL at an early stage, in rectal cancer and adenoma, and in colorectal tumors with poor prognosis
    tumoral somatic mutation      
    in high hyperdiploid childhood acute lymphoblastic leukemia
    tumoral somatic mutation      
    promotes colon cancer progression (mutation arise after loss of APC during colon cancer progression)
    tumoral somatic mutation      
    in colorectal cancer is correlated with increased proliferation and spontaneous apoptosis
    tumoral somatic mutation     gain of function
    activating mutations in the KRAS gene impair the ability of the KRAS protein to switch between active and inactive states, leading to cell transformation and increased resistance to chemotherapy and biological therapies targeting epidermal growth factor receptor
    tumoral somatic mutation     gain of function
    activating KRAS mutations is significantly correlated to an upregulation of 13 genes among them DUSP4, a MAP-kinase phosphatase, and SMYD3 in colorectal cancer
    tumoral somatic mutation      
    in autoimmune lymphoproliferative syndrome
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    importance of KRAS alterations as a potential therapeutic target for Colorectal cancer
    osteoarticular  
    RAS/ERK1/2 inhibition could be a potent strategy to treat RASopathies, including Noonan sdr
    cancerdigestivepancreas
    therapy target in pancreatic ductal adenocarcinoma (PDAC)
    ANIMAL & CELL MODELS