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FLASH GENE
Symbol HRAS contributors: mct/pgu - updated : 27-03-2019
HGNC name v-Ha-ras Harvey rat sarcoma viral oncogene homolog
HGNC id 5173
Corresponding disease
COSTS Costello syndrome
SMPS1 Schimmelpenning syndrome 1
Location 11p15.5      Physical location : 532.242 - 535.550
Synonym name
  • c-has/bas p21 protein
  • c-ras-Ki-2 protein
  • p21 protein
  • Ha-Ras1 proto-oncoprotein
  • p19 H-RasIDX protein
    • Synonym symbol(s) HRAS1, RASH, K-ras, N-ras, RASH1, c-bas/has, HAMSV, RAS, CTLO, p21ras
    DNA
    TYPE functioning gene
    STRUCTURE 3.31 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence
    text structure
  • including 1a,1b,1c
  • repetition of GGGCCT in intron 1
    • MAPPING cloned Y linked Y status confirmed
    Map see INS ,PTH PTH
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 1061 21 189 - 2012 22707223
    7 - 1251 - 170 - 2012 22707223
    5 - 1169 21 189 - 2012 22707223
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Digestivemouthtongue  highly
     salivary gland   highly
    Nervousbrain   moderately
    Respiratorylung   moderately
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    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
  • C-terminal HVR, especially the flexible linker domain with two consecutive proline residues Pro173 and Pro174, is a critical domain contributing to activation of HRAS and its invasive potential in breast epithelial cells
    • HOMOLOGY
    interspecies homolog to rattus Harvey sarcoma viral (v-Ha-ras1) oncogene
    intraspecies homolog to KRAS2
    homolog to NRAS
    homolog to RRAS2
    Homologene
    FAMILY
  • small GTPase superfamily
  • RAS family
    • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text attached to the membrane by a lipid anchor and shuttles between the internal side of plasma membrane and the golgi
    basic FUNCTION
  • binding GDP/GTP and possessing intrinsic GTPase activity
  • tumor type-specific mutation spectrum of Ras genesis dictated by their regulation of expression and that the altered Ras proteins that can be palmitoylated act as particularly potent oncoproteins
  • potent cell-autonomous negative regulator of the HH pathway, supporting an important role for paracrine HH signaling in tumors harboring KRAS mutations, such as those in lung and pancreatic cancer
  • activated HRAS can be found in primary cilia, the central organelle of HH signal transduction, but functions in a cilium-independent manner and interferes with GLI2 function and GLI3 processing
  • could modulate fibroblast activity by reducing ECM synthesis and upregulating both proliferation and migration
  • proto-oncogene that activates a variety of different pathways including the extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase pathway
  • involved primarily in regulating cell growth, division and apoptosis
  • relays signals from outside of the cell to the cell nucleus
  • newly recognized role for endomembrane-localized HRAS in mediating nitric oxide-dependent proangiogenic signaling
    • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    text cell cycle contr
    le
    PATHWAY
    metabolism
    signaling signal transduction
  • HRAS-PI3K signaling pathway targets specific epigenetic modifications in tumor cells
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction with PMAIP1 and BECN1 (HRAS-induced expression of PMAIP1 and Beclin-1 promotes autophagic cell death)
  • DPP9 and DPP8, associate with HRAS, a key signal molecule of the EGF receptor signaling pathway, suggesting an important signaling role of DPP9 in the regulation of survival and proliferation pathways
  • BNIP3 is a regulatory target of HRAS
  • regulates BRIP1 expression to induce dissociation of BRCA1 from chromatin, inhibit DNA repair, and promote senescence
  • PEA15 positively regulates HRAS/ERK signaling and increases the proliferation of HRAS-transformed epithelial cells through enhanced PLD1 expression and activation
  • CHST11 is a negatively regulated target gene of HRAS signaling
  • novel interplay between KRAS and HRAS, with possible implications for colorectal carcinogenesis
  • critical role of BACH1 in cell transformation and tumor growth induced by activated HRAS
  • TP53BP2 modulates oncogenic HRAS-induced autophagic activity to dictate the cellular response to HRAS: to proliferate or senescence
  • HRAS mediates VEGFA-induced activation of endothelial nitric-oxide synthase (NOS3) and migratory response of human endothelial cells
  • CIP2A physically associates with HRAS, which leads to the activation of the MEK/ERK signaling pathway and promotes EMT and cervical-cancer progression
  • HRAS downregulated thymine-DNA glycosylase (TDG), a DNA demethylation enzyme, by inhibiting the interaction of transcription activator ING4 with TDG promoter
  • role for CIB1 in neoplastic transformation, revaeling a novel mechanism facilitating oncogenic signalling by HRAS and PAPSS1
  • LZTR1-mediated ubiquitination inhibited RAS signaling by attenuating its association with the membrane
  • LZTR1 facilitates polyubiquitination and degradation of RAS-GTPases MRAS, HRAS, NRAS, and KRAS
  • cytosolic EPCAM cooperates with HRAS to regulate epithelial to mesenchymal transition through ZEB1
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) COSTS , SMPS1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in bladder cancer and in sporadic invasive breast cancer
    tumoral somatic mutation      
    in dedifferentiated liposarcoma and in papillary thyroid cancer with with poor prognosis
    tumoral       gain of function
    mutation activating in spermatocytic seminomas
    tumoral     --over  
    often associated with tumor aggressiveness in breast cancer
    Susceptibility
    Variant & Polymorphism repeat three GGGCCT repeats
    Candidate gene
    Marker
  • abnormal methylation of the HRAS gene may be an early event during urocystic tumorigenesis and may be further used as a cancer biomarker in bladder tissue for early diagnosis
    • Therapy target
    SystemTypeDisorderPubmed
    cancerurinary 
    abnormal methylation of the HRAS gene may be further used as a potential therapeutic target
    ANIMAL & CELL MODELS