Atlas of Genetics and Cytogenetics in Oncology and Haematology

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HRAS (Harvey rat sarcoma viral oncogene homolog)

Identity

Other namesc-Ha-ras 1
HGNC (Hugo) HRAS
LocusID (NCBI) 3265
Location 11p15.5
Location_base_pair Starts at 532242 and ends at 535550 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Note more on the RAS family is available as a deep insight.

DNA/RNA

Note to be quoted is the existence of a pseudogene, c-Ha-ras 2, inactivated, processed pseudogene which is located on Chromosome X.
 
  H-ras splicing variants : alternative splicing of H-ras precursor mRNA leads to the two transcripts p19 and p21 which differ by the ex- or inclusion of the Intron D Exon (IDX); 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 6.6kb of genomic DNA
Transcription alternative RNA splicing reveals two different transcripts (see Fig); if the Intron D Exon (IDX) is skipped exon 4 is directly joined to exon 3

Protein

Description 170 amino acids; 19kDa; shares a common effector region with regular RAS proteins; absence of residues 152-165, abrogating the GDP/GTP binding, and lack of a cysteine residue in the carboxy-terminus preventing the posttranslational modifications essential for the attachment of RAS proteins to the cytoplasmic membrane regular RAS protein - characterized in the RAS family page
Expression p19H-ras is expected to be produced at a much higher level than p21H-ras; the surprising low abundance of p19H-ras could be explained by instability of mRNA or unproductive splicing ubiquitously expressed
Localisation cytoplasmic anchored to the inner surface of the plasma membrane
Function no oncogenic ability; it has been assumed, that p19H-ras might act as a antagonist to p21H-ras; due to the intact effector region it would interact constitutively with candidate effector molecules or regulators such as GAP, thereby suppressing the biological function of p21H-ras; additionally the expression of p19H-ras was found to limit the production of p21H-ras 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, RAL, RAC, RHO, RAP, and RAB 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 with RAS proteins.

Implicated in

Entity tumor (frequency of H-RAS mutations); references in Full Bibliography
  
Entity stomach (0-40%)
  
Entity urinary bladder (0-65%)
  
Entity prostate (0-10%)
  
Entity skin (0-45%)
  
Entity thyroid (0-60%)
  
Entity breast (0-10%)
  
Entity head and neck (0-30%)
  
Entity endometrium (5%)
  

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

Solid Tumors ProstateOverviewID5041 ProstateOverviewID5041 ProstateOverviewID5041 ProstateOverviewID5041 ProstateOverviewID5041
softissuTumID5042 ProstateOverviewID5041

External links

Nomenclature
HGNC (Hugo)HRAS   5173
Cards
AtlasHRASID108
Entrez_Gene (NCBI)HRAS  3265  Harvey rat sarcoma viral oncogene homolog
GeneCards (Weizmann)HRAS
Ensembl (Hinxton)ENSG00000174775 [Gene_View]  chr11:532242-535550 [Contig_View]  HRAS [Vega]
ICGC DataPortalENSG00000174775
cBioPortalHRAS
AceView (NCBI)HRAS
Genatlas (Paris)HRAS
WikiGenes3265
SOURCE (Princeton)NM_001130442 NM_005343 NM_176795
Genomic and cartography
GoldenPath (UCSC)HRAS  -  11p15.5   chr11:532242-535550 -  11p15.5   [Description]    (hg19-Feb_2009)
EnsemblHRAS - 11p15.5 [CytoView]
Mapping of homologs : NCBIHRAS [Mapview]
OMIM109800   162900   163200   188470   190020   218040   
Gene and transcription
Genbank (Entrez)AB451336 AB451485 AF493916 AJ437024 BC006499
RefSeq transcript (Entrez)NM_001130442 NM_005343 NM_176795
RefSeq genomic (Entrez)AC_000143 NC_000011 NC_018922 NG_007666 NT_009237 NW_001838016 NW_004929378
Consensus coding sequences : CCDS (NCBI)HRAS
Cluster EST : UnigeneHs.37003 [ NCBI ]
CGAP (NCI)Hs.37003
Alternative Splicing : Fast-db (Paris)GSHG0005437
Alternative Splicing GalleryENSG00000174775
Gene ExpressionHRAS [ NCBI-GEO ]     HRAS [ SEEK ]   HRAS [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP01112 (Uniprot)
NextProtP01112  [Medical]
With graphics : InterProP01112
Splice isoforms : SwissVarP01112 (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 : CluSTrP01112
Domain families : Pfam (Sanger)Ras (PF00071)   
Domain families : Pfam (NCBI)pfam00071   
Domain families : Smart (EMBL)RAS (SM00173)  
DMDM Disease mutations3265
Blocks (Seattle)P01112
PDB (SRS)121P    1AA9    1AGP    1BKD    1CLU    1CRP    1CRQ    1CRR    1CTQ    1GNP    1GNQ    1GNR    1HE8    1IAQ    1IOZ    1JAH    1JAI    1K8R    1LF0    1LF5    1LFD    1NVU    1NVV    1NVW    1NVX    1P2S    1P2T    1P2U    1P2V    1PLJ    1PLK    1PLL    1Q21    1QRA    1RVD    1WQ1    1XCM    1XD2    1XJ0    1ZVQ    1ZW6    221P    2C5L    2CE2    2CL0    2CL6    2CL7    2CLC    2CLD    2EVW    2GDP    2LCF    2LWI    2Q21    2QUZ    2RGA    2RGB    2RGC    2RGD    2RGE    2RGG    2UZI    2VH5    2X1V    3DDC    3I3S    3K8Y    3K9L    3K9N    3KKM    3KKN    3KUD    3L8Y    3L8Z    3LBH    3LBI    3LBN    3LO5    3OIU    3OIV    3OIW    3RRY    3RRZ    3RS0    3RS2    3RS3    3RS4    3RS5    3RS7    3RSL    3RSO    3TGP    421P    4DLR    4DLS    4DLT    4DLU    4DLV    4DLW    4DLX    4DLY    4DLZ    4DST    4DSU    4EFL    4EFM    4EFN    4G0N    4G3X    4Q21    521P    5P21    621P    6Q21    721P    821P   
PDB (PDBSum)121P    1AA9    1AGP    1BKD    1CLU    1CRP    1CRQ    1CRR    1CTQ    1GNP    1GNQ    1GNR    1HE8    1IAQ    1IOZ    1JAH    1JAI    1K8R    1LF0    1LF5    1LFD    1NVU    1NVV    1NVW    1NVX    1P2S    1P2T    1P2U    1P2V    1PLJ    1PLK    1PLL    1Q21    1QRA    1RVD    1WQ1    1XCM    1XD2    1XJ0    1ZVQ    1ZW6    221P    2C5L    2CE2    2CL0    2CL6    2CL7    2CLC    2CLD    2EVW    2GDP    2LCF    2LWI    2Q21    2QUZ    2RGA    2RGB    2RGC    2RGD    2RGE    2RGG    2UZI    2VH5    2X1V    3DDC    3I3S    3K8Y    3K9L    3K9N    3KKM    3KKN    3KUD    3L8Y    3L8Z    3LBH    3LBI    3LBN    3LO5    3OIU    3OIV    3OIW    3RRY    3RRZ    3RS0    3RS2    3RS3    3RS4    3RS5    3RS7    3RSL    3RSO    3TGP    421P    4DLR    4DLS    4DLT    4DLU    4DLV    4DLW    4DLX    4DLY    4DLZ    4DST    4DSU    4EFL    4EFM    4EFN    4G0N    4G3X    4Q21    521P    5P21    621P    6Q21    721P    821P   
PDB (IMB)121P    1AA9    1AGP    1BKD    1CLU    1CRP    1CRQ    1CRR    1CTQ    1GNP    1GNQ    1GNR    1HE8    1IAQ    1IOZ    1JAH    1JAI    1K8R    1LF0    1LF5    1LFD    1NVU    1NVV    1NVW    1NVX    1P2S    1P2T    1P2U    1P2V    1PLJ    1PLK    1PLL    1Q21    1QRA    1RVD    1WQ1    1XCM    1XD2    1XJ0    1ZVQ    1ZW6    221P    2C5L    2CE2    2CL0    2CL6    2CL7    2CLC    2CLD    2EVW    2GDP    2LCF    2LWI    2Q21    2QUZ    2RGA    2RGB    2RGC    2RGD    2RGE    2RGG    2UZI    2VH5    2X1V    3DDC    3I3S    3K8Y    3K9L    3K9N    3KKM    3KKN    3KUD    3L8Y    3L8Z    3LBH    3LBI    3LBN    3LO5    3OIU    3OIV    3OIW    3RRY    3RRZ    3RS0    3RS2    3RS3    3RS4    3RS5    3RS7    3RSL    3RSO    3TGP    421P    4DLR    4DLS    4DLT    4DLU    4DLV    4DLW    4DLX    4DLY    4DLZ    4DST    4DSU    4EFL    4EFM    4EFN    4G0N    4G3X    4Q21    521P    5P21    621P    6Q21    721P    821P   
PDB (RSDB)121P    1AA9    1AGP    1BKD    1CLU    1CRP    1CRQ    1CRR    1CTQ    1GNP    1GNQ    1GNR    1HE8    1IAQ    1IOZ    1JAH    1JAI    1K8R    1LF0    1LF5    1LFD    1NVU    1NVV    1NVW    1NVX    1P2S    1P2T    1P2U    1P2V    1PLJ    1PLK    1PLL    1Q21    1QRA    1RVD    1WQ1    1XCM    1XD2    1XJ0    1ZVQ    1ZW6    221P    2C5L    2CE2    2CL0    2CL6    2CL7    2CLC    2CLD    2EVW    2GDP    2LCF    2LWI    2Q21    2QUZ    2RGA    2RGB    2RGC    2RGD    2RGE    2RGG    2UZI    2VH5    2X1V    3DDC    3I3S    3K8Y    3K9L    3K9N    3KKM    3KKN    3KUD    3L8Y    3L8Z    3LBH    3LBI    3LBN    3LO5    3OIU    3OIV    3OIW    3RRY    3RRZ    3RS0    3RS2    3RS3    3RS4    3RS5    3RS7    3RSL    3RSO    3TGP    421P    4DLR    4DLS    4DLT    4DLU    4DLV    4DLW    4DLX    4DLY    4DLZ    4DST    4DSU    4EFL    4EFM    4EFN    4G0N    4G3X    4Q21    521P    5P21    621P    6Q21    721P    821P   
Human Protein AtlasENSG00000174775 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP01112
HPRD01813
IPIIPI00000006   IPI00741763   IPI00979370   
Protein Interaction databases
DIP (DOE-UCLA)P01112
IntAct (EBI)P01112
FunCoupENSG00000174775
BioGRIDHRAS
InParanoidP01112
Interologous Interaction database P01112
IntegromeDBHRAS
STRING (EMBL)HRAS
Ontologies - Pathways
Ontology : AmiGOGolgi membrane  MAPK cascade  activation of MAPKK activity  positive regulation of protein phosphorylation  GTPase activity  protein binding  GTP binding  nucleus  cytoplasm  Golgi apparatus  cytosol  plasma membrane  plasma membrane  endocytosis  chemotaxis  cell cycle arrest  cell cycle arrest  mitotic cell cycle checkpoint  signal transduction  cell surface receptor signaling pathway  epidermal growth factor receptor signaling pathway  small GTPase mediated signal transduction  Ras protein signal transduction  Ras protein signal transduction  synaptic transmission  axon guidance  blood coagulation  protein C-terminus binding  cell proliferation  positive regulation of cell proliferation  negative regulation of cell proliferation  insulin receptor signaling pathway  visual learning  fibroblast growth factor receptor signaling pathway  organ morphogenesis  negative regulation of gene expression  actin cytoskeleton organization  positive regulation of cell migration  regulation of synaptic transmission, GABAergic  positive regulation of Rac GTPase activity  negative regulation of Rho GTPase activity  positive regulation of Rac protein signal transduction  social behavior  Fc-epsilon receptor signaling pathway  positive regulation of MAP kinase activity  positive regulation of MAPK cascade  negative regulation of neuron apoptotic process  innate immune response  positive regulation of DNA replication  positive regulation of transcription from RNA polymerase II promoter  positive regulation of JNK cascade  neurotrophin TRK receptor signaling pathway  regulation of long-term neuronal synaptic plasticity  perinuclear region of cytoplasm  positive regulation of epithelial cell proliferation  leukocyte migration  striated muscle cell differentiation  protein heterooligomerization  positive regulation of ERK1 and ERK2 cascade  positive regulation of wound healing  cellular senescence  intrinsic apoptotic signaling pathway  positive regulation of ruffle assembly  positive regulation of actin cytoskeleton reorganization  positive regulation of miRNA metabolic process  
Ontology : EGO-EBIGolgi membrane  MAPK cascade  activation of MAPKK activity  positive regulation of protein phosphorylation  GTPase activity  protein binding  GTP binding  nucleus  cytoplasm  Golgi apparatus  cytosol  plasma membrane  plasma membrane  endocytosis  chemotaxis  cell cycle arrest  cell cycle arrest  mitotic cell cycle checkpoint  signal transduction  cell surface receptor signaling pathway  epidermal growth factor receptor signaling pathway  small GTPase mediated signal transduction  Ras protein signal transduction  Ras protein signal transduction  synaptic transmission  axon guidance  blood coagulation  protein C-terminus binding  cell proliferation  positive regulation of cell proliferation  negative regulation of cell proliferation  insulin receptor signaling pathway  visual learning  fibroblast growth factor receptor signaling pathway  organ morphogenesis  negative regulation of gene expression  actin cytoskeleton organization  positive regulation of cell migration  regulation of synaptic transmission, GABAergic  positive regulation of Rac GTPase activity  negative regulation of Rho GTPase activity  positive regulation of Rac protein signal transduction  social behavior  Fc-epsilon receptor signaling pathway  positive regulation of MAP kinase activity  positive regulation of MAPK cascade  negative regulation of neuron apoptotic process  innate immune response  positive regulation of DNA replication  positive regulation of transcription from RNA polymerase II promoter  positive regulation of JNK cascade  neurotrophin TRK receptor signaling pathway  regulation of long-term neuronal synaptic plasticity  perinuclear region of cytoplasm  positive regulation of epithelial cell proliferation  leukocyte migration  striated muscle cell differentiation  protein heterooligomerization  positive regulation of ERK1 and ERK2 cascade  positive regulation of wound healing  cellular senescence  intrinsic apoptotic signaling pathway  positive regulation of ruffle assembly  positive regulation of actin cytoskeleton reorganization  positive regulation of miRNA metabolic process  
Pathways : BIOCARTACalcium Signaling by HBx of Hepatitis B virus [Genes]    Bioactive Peptide Induced Signaling Pathway [Genes]    Cadmium induces DNA synthesis and proliferation in macrophages [Genes]    EGF Signaling Pathway [Genes]    Erk1/Erk2 Mapk Signaling pathway [Genes]    Keratinocyte Differentiation [Genes]    mCalpain and friends in Cell motility [Genes]    Inhibition of Matrix Metalloproteinases [Genes]    Influence of Ras and Rho proteins on G1 to S Transition [Genes]    BCR Signaling Pathway [Genes]    IL 2 signaling pathway [Genes]    How Progesterone Initiates the Oocyte Maturation [Genes]    NFAT and Hypertrophy of the heart (Transcription in the broken heart) [Genes]    T Cell Receptor Signaling Pathway [Genes]    Trefoil Factors Initiate Mucosal Healing [Genes]    Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling [Genes]    Role of EGF Receptor Transactivation by GPCRs in Cardiac Hypertrophy [Genes]    Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia [Genes]    fMLP induced chemokine gene expression in HMC-1 cells [Genes]    Role of MAL in Rho-Mediated Activation of SRF [Genes]    Ras Signaling Pathway [Genes]    Aspirin Blocks Signaling Pathway Involved in Platelet Activation [Genes]    Integrin Signaling Pathway [Genes]    MAPKinase Signaling Pathway [Genes]    Inhibition of Cellular Proliferation by Gleevec [Genes]    IGF-1 Signaling Pathway [Genes]    IL 3 signaling pathway [Genes]    IL 6 signaling pathway [Genes]    Links between Pyk2 and Map Kinases [Genes]    Trka Receptor Signaling Pathway [Genes]    Phosphorylation of MEK1 by cdk5/p35 down regulates the MAP kinase pathway [Genes]    EPO Signaling Pathway [Genes]    Role of Erk5 in Neuronal Survival [Genes]    Signaling of Hepatocyte Growth Factor Receptor [Genes]    Regulation of transcriptional activity by PML [Genes]    Regulation of Splicing through Sam68 [Genes]    CCR3 signaling in Eosinophils [Genes]    TPO Signaling Pathway [Genes]    CXCR4 Signaling Pathway [Genes]    Fc Epsilon Receptor I Signaling in Mast Cells [Genes]    Growth Hormone Signaling Pathway [Genes]    Signaling Pathway from G-Protein Families [Genes]    Insulin Signaling Pathway [Genes]    The IGF-1 Receptor and Longevity [Genes]    p38 MAPK Signaling Pathway [Genes]    Sprouty regulation of tyrosine kinase signals [Genes]    Roles of ø-arrestin-dependent Recruitment of Src Kinases in GPCR Signaling [Genes]    Transcription factor CREB and its extracellular signals [Genes]    METS affect on Macrophage Differentiation [Genes]    Role of ERBB2 in Signal Transduction and Oncology [Genes]    Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]    Nerve growth factor pathway (NGF) [Genes]    PDGF Signaling Pathway [Genes]    VEGF, Hypoxia, and Angiogenesis [Genes]   
Pathways : KEGGMAPK signaling pathway    ErbB signaling pathway    Ras signaling pathway    Rap1 signaling pathway    Chemokine signaling pathway    FoxO signaling pathway    Endocytosis    PI3K-Akt signaling pathway    Axon guidance    VEGF signaling pathway    Focal adhesion    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    Estrogen signaling pathway    Melanogenesis    Prolactin signaling pathway    Thyroid hormone signaling pathway    Alcoholism    Hepatitis C    Hepatitis B    HTLV-I infection    Pathways in cancer    Viral carcinogenesis    Proteoglycans in cancer    MicroRNAs in cancer    Renal cell carcinoma    Endometrial cancer    Glioma    Prostate cancer    Thyroid cancer    Melanoma    Bladder cancer    Chronic myeloid leukemia    Acute myeloid leukemia    Non-small cell lung cancer   
Protein Interaction DatabaseHRAS
Wikipedia pathwaysHRAS
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)HRAS
snp3D : Map Gene to Disease3265
SNP (GeneSNP Utah)HRAS
SNP : HGBaseHRAS
Genetic variants : HAPMAPHRAS
Exome VariantHRAS
1000_GenomesHRAS 
ICGC programENSG00000174775 
Cancer Gene: CensusHRAS 
Somatic Mutations in Cancer : COSMICHRAS 
CONAN: Copy Number AnalysisHRAS 
Mutations and Diseases : HGMDHRAS
Genomic VariantsHRAS  HRAS [DGVbeta]
dbVarHRAS
ClinVarHRAS
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM109800    162900    163200    188470    190020    218040   
MedgenHRAS
GENETestsHRAS
Disease Genetic AssociationHRAS
Huge Navigator HRAS [HugePedia]  HRAS [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneHRAS
Homology/Alignments : Family Browser (UCSC)HRAS
Phylogenetic Trees/Animal Genes : TreeFamHRAS
Chemical/Protein Interactions : CTD3265
Chemical/Pharm GKB GenePA29444
Drug Sensitivity HRAS
Clinical trialHRAS
Cancer Resource (Charite)ENSG00000174775
Other databases
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=HRAS
Probes
ProbeCancer Cytogenetics (Bari)
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineHRAS
iHOPHRAS

Bibliography

A position 12-activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient.
Kraus MH, Yuasa Y, Aaronson SA
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Spandidos DA
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PMID 3144694
 
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PMID 2667764
 
High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis.
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Infrequent point mutations of ras oncogenes in gastric cancers.
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Low incidence of ras oncogene activation in human squamous cell carcinomas.
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PMID 2183872
 
No evidence for point mutations in codons 12, 13, and 61 of the ras gene in a high-incidence area for esophageal and gastric cancers.
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Activated ras alleles in human carcinoma of the prostate are rare.
Gumerlock PH, Poonamallee UR, Meyers FJ, deVere White RW
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K-ras activation in gastric epithelial tumors in Japanese.
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High frequency mutation in codons 12 and 61 of H-ras oncogene in chewing tobacco-related human oral carcinoma in India.
Saranath D, Chang SE, Bhoite LT, Panchal RG, Kerr IB, Mehta AR, Johnson NW, Deo MG
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PMID 2021541
 
ras activation in experimental carcinogenesis.
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PMID 1421167
 
Mapping of UV photoproducts within ras proto-oncogenes in UV-irradiated cells: correlation with mutations in human skin cancer.
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PMID 1501884
 
Codon 12 Harvey-ras mutations are rare events in non-melanoma human skin cancer.
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PMID 8096149
 
The absence of Harvey ras mutations during development and progression of squamous cell carcinomas of the head and neck.
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Ras oncogene mutations in thyroid tumors: polymerase chain reaction-restriction-fragment-length polymorphism analysis from paraffin-embedded tissues.
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A PCR-RFLP method for the detection of activated H-ras oncogene with a point mutation at codon 12 and 61.
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ras gene mutations in human endometrial carcinoma.
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A splicing enhancer in the 3'-terminal c-H-ras exon influences mRNA abundance and transforming activity.
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Written02-1999Franz Watzinger and Thomas Lion
Childrenīs Cancer Research Institute, Kinderspitalgasse 6, A-1090 Vienna, Austria

Citation

This paper should be referenced as such :
Watzinger, F ; Lion, T
HRAS (Harvey rat sarcoma viral oncogene homolog)
Atlas Genet Cytogenet Oncol Haematol. 1999;3(2):63-65.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/HRASID108.html

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