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HRAS (Harvey rat sarcoma viral oncogene homolog)

Identity

Other namesc-Ha-ras 1
HGNC (Hugo) HRAS
Location 11p15.5
Location_base_pair Starts at 532637 and ends at 534322 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%)
  

External links

Nomenclature
HGNC (Hugo)HRAS   5173
Entrez_Gene (NCBI)HRAS  3265  v-Ha-ras Harvey rat sarcoma viral oncogene homolog
Cards
AtlasHRASID108
GeneCards (Weizmann)HRAS
Ensembl (Hinxton)ENSG00000174775 [Gene_View]  HRAS [Vega]
AceView (NCBI)HRAS
Genatlas (Paris)HRAS
euGene (Indiana)3265
SOURCE (Stanford)NM_001130442 NM_005343 NM_176795
Gene Expression (Array Express) ENSG00000174775
Genomic and cartography
GoldenPath (UCSC)HRAS  -  11p15.5   chr11:532637-534322 -  11p15.5   [Description]    (hg19-Feb_2009)
EnsemblHRAS - 11p15.5 [CytoView]
Mapping of homologs : NCBIHRAS [Mapview]
OMIM109800   188470   190020   218040   
Gene and transcription
Gene : Genbank (Entrez)AB451336 AB451485 AF493916 AJ437024 BC006499
Reference sequence (RefSeq transcript) :SRSNM_001130442 NM_005343 NM_176795
Reference transcript : EntrezNM_001130442 NM_005343 NM_176795
RefSeq genomic : SRSAC_000054 AC_000143 NC_000011 NG_007666 NT_009237 NW_001838016 NW_924962
RefSeq genomic : EntrezAC_000054 AC_000143 NC_000011 NG_007666 NT_009237 NW_001838016 NW_924962
Consensus coding sequences : CCDS NCBIHRAS
Cluster EST : UnigeneHs.37003 [ SRS ] Hs.37003 [ NCBI ]
Alternative Splicing : Fast-db (Paris)290
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP01112 (SRS) P01112 (Expasy) P01112 (Uniprot)
With graphics : InterProP01112
Splice isoforms : VarSplice FASTAP01112(VarSplice FASTA)
Domaine pattern : Prosite (SRS)RAS (PS51421)   
Domain pattern : Prosite (Expaxy)RAS (PS51421)   
Domains : Interpro (SRS)GTPase_Ras    Ras    Ras_GTPase    Ras_Ras_related    Ras_small_GTPase    Small_GTP-bd   
Domains : Interpro (EBI)GTPase_Ras    Ras    Ras_GTPase    Ras_Ras_related    Ras_small_GTPase    Small_GTP-bd   
Related proteins : CluSTrP01112
Domain families : Pfam SRSRas (PF00071)   
Domain families : Pfam SangerRas (PF00071)   
Domain families : Pfam NCBIpfam00071   
Domain families : Smart EMBLRAS (SM00173)  
Blocks (Seattle)P01112
Crystal structure of protein : PDB SRS121P    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    2Q21    2QUZ    2RGA    2RGB    2RGC    2RGD    2RGE    2RGG    2UZI    2VH5    2X1V    3DDC    3I3S    3K8Y    3K9N    3KUD    3LBH    3LBI    3LBN    3LO5    421P    4Q21    521P    5P21    621P    6Q21    721P    821P   
Crystal structure of protein : PDBSum121P    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    2Q21    2QUZ    2RGA    2RGB    2RGC    2RGD    2RGE    2RGG    2UZI    2VH5    2X1V    3DDC    3I3S    3K8Y    3K9N    3KUD    3LBH    3LBI    3LBN    3LO5    421P    4Q21    521P    5P21    621P    6Q21    721P    821P   
Crystal structure of protein : IMB121P    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    2Q21    2QUZ    2RGA    2RGB    2RGC    2RGD    2RGE    2RGG    2UZI    2VH5    2X1V    3DDC    3I3S    3K8Y    3K9N    3KUD    3LBH    3LBI    3LBN    3LO5    421P    4Q21    521P    5P21    621P    6Q21    721P    821P   
Crystal structure of protein : PDB RSDB121P    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    2Q21    2QUZ    2RGA    2RGB    2RGC    2RGD    2RGE    2RGG    2UZI    2VH5    2X1V    3DDC    3I3S    3K8Y    3K9N    3KUD    3LBH    3LBI    3LBN    3LO5    421P    4Q21    521P    5P21    621P    6Q21    721P    821P   
Human Protein AtlasENSG00000174775
HPRD01813
Protein Interaction databases
DIP (DOE-UCLA)P01112
IntAct (EBI)P01112
FunCoupENSG00000174775
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIHRAS
SNP : GeneSNP UtahHRAS
SNP : HGBaseHRAS
Genetic variants : HAPMAPHRAS
Cancer Gene: CensusHRAS 
Somatic Mutations in Cancer : COSMICHRAS 
Mutations and Diseases : HGMDHRAS
Hereditary diseases : OMIM109800    188470    190020    218040   
Hereditary diseases : GENETests109800    188470    190020    218040   
Diseases : Genetic AssociationHRAS
General knowledge
Homologs : HomoloGeneHRAS
Homology/Alignments : Family Browser UCSCHRAS
Phylogenetic Trees/Animal Genes : TreeFamHRAS
Chemical/Protein Interactions : CTD3265
Keywords Ontology : AmiGOGolgi membrane  nucleotide binding  GTPase activity  protein binding  GTP binding  intracellular  soluble fraction  cytoplasm  microsome  Golgi apparatus  cytosol  plasma membrane  apoptosis  chemotaxis  cell cycle arrest  cell cycle arrest  signal transduction  cell surface receptor linked signaling pathway  small GTPase mediated signal transduction  Ras protein signal transduction  protein C-terminus binding  positive regulation of cell proliferation  negative regulation of cell proliferation  organ morphogenesis  G1/S transition checkpoint  social behavior  positive regulation of MAPKKK cascade  positive regulation of DNA replication  protein heterooligomerization  positive regulation of ERK1 and ERK2 cascade  
Keywords Ontology : EGO-EBIGolgi membrane  nucleotide binding  GTPase activity  protein binding  GTP binding  intracellular  soluble fraction  cytoplasm  microsome  Golgi apparatus  cytosol  plasma membrane  apoptosis  chemotaxis  cell cycle arrest  cell cycle arrest  signal transduction  cell surface receptor linked signaling pathway  small GTPase mediated signal transduction  Ras protein signal transduction  protein C-terminus binding  positive regulation of cell proliferation  negative regulation of cell proliferation  organ morphogenesis  G1/S transition checkpoint  social behavior  positive regulation of MAPKKK cascade  positive regulation of DNA replication  protein heterooligomerization  positive regulation of ERK1 and ERK2 cascade  
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 ?-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 : KEGGInsulin signaling pathwayFc epsilon RI signaling pathwayB cell receptor signaling pathwayT cell receptor signaling pathwayVEGF signaling pathwayGnRH signaling pathwayTight junctionAxon guidanceLong-term depressionRegulation of actin cytoskeletonFocal adhesionLong-term potentiationMAPK signaling pathwayNatural killer cell mediated cytotoxicityGap junction
Other databases
Probes
ProbeCancer Cytogenetics (Bari)
Probes : ImagenesHRAS Related clones (RZPD - Berlin)
Literature
PubMed408 Pubmed reference(s) in Entrez
PubGeneHRAS

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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PMID 6089200
 
Oncogenes and bladder cancer.
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A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases.
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Human cancer and cellular oncogenes.
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PMID 3307760
 
Oncogene activation in malignant transformation: a study of H-ras in human breast cancer.
Spandidos DA
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PMID 3435051
 
Activated ras oncogenes in human thyroid cancers.
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PMID 2667764
 
High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis.
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ras gene mutations in human prostate cancer.
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Infrequent point mutations of ras oncogenes in gastric cancers.
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PMID 2179035
 
Low incidence of ras oncogene activation in human squamous cell carcinomas.
Rumsby G, Carter RL, Gusterson BA
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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.
Victor T, Du Toit R, Jordaan AM, Bester AJ, van Helden PD
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PMID 2199031
 
Correlation of mutations of oncogene C-Ha-ras at codon 12 with metastasis and survival of gastric cancer patients.
Deng GR, Liu XH, Wang JR
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PMID 1671796
 
Activated ras alleles in human carcinoma of the prostate are rare.
Gumerlock PH, Poonamallee UR, Meyers FJ, deVere White RW
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PMID 1998954
 
K-ras activation in gastric epithelial tumors in Japanese.
Miki H, Ohmori M, Perantoni AO, Enomoto T
Cancer letters. 1991 ; 58 (1-2) : 107-113.
PMID 2049776
 
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.
Tˆrmˆ§nen VT, Pfeifer GP
Oncogene. 1992 ; 7 (9) : 1729-1736.
PMID 1501884
 
Codon 12 Harvey-ras mutations are rare events in non-melanoma human skin cancer.
Campbell C, Quinn AG, Rees JL
The British journal of dermatology. 1993 ; 128 (2) : 111-114.
PMID 8096149
 
The absence of Harvey ras mutations during development and progression of squamous cell carcinomas of the head and neck.
Clark LJ, Edington K, Swan IR, McLay KA, Newlands WJ, Wills LC, Young HA, Johnston PW, Mitchell R, Robertson G
British journal of cancer. 1993 ; 68 (3) : 617-620.
PMID 8353052
 
Mutations, expression and genomic instability of the H-ras proto-oncogene in squamous cell carcinomas of the head and neck.
Kiaris H, Spandidos DA, Jones AS, Vaughan ED, Field JK
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PMID 7599040
 
Ras oncogene mutations in thyroid tumors: polymerase chain reaction-restriction-fragment-length polymorphism analysis from paraffin-embedded tissues.
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PMID 8919545
 
A PCR-RFLP method for the detection of activated H-ras oncogene with a point mutation at codon 12 and 61.
Hong SJ, Lee T, Park YS, Lee KO, Chung BH, Lee SH
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PMID 9048488
 
ras gene mutations in human endometrial carcinoma.
Varras MN, Koffa M, Koumantakis E, Ergazaki M, Protopapa E, Michalas S, Spandidos DA
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PMID 8960147
 
A splicing enhancer in the 3'-terminal c-H-ras exon influences mRNA abundance and transforming activity.
Hwang DY, Cohen JB
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PMID 9261359
 
Mutation of ras oncogene in gastric adenocarcinoma: association with histological phenotype.
Kim TY, Bang YJ, Kim WS, Kang SH, Lee KU, Choe KJ, Kim NK
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PMID 9137494
 
Comparison of ras activation in prostate carcinoma in Japanese and American men.
Konishi N, Hiasa Y, Tsuzuki T, Tao M, Enomoto T, Miller GJ
The Prostate. 1997 ; 30 (1) : 53-57.
PMID 9018336
 
Screening of H-ras gene point mutations in 50 cases of bladder carcinoma.
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International journal of urology : official journal of the Japanese Urological Association. 1997 ; 4 (2) : 178-185.
PMID 9179693
 
Variability of Ha-ras (codon 12) proto-oncogene mutations in diverse thyroid cancers.
Bouras M, Bertholon J, Dutrieux-Berger N, Parvaz P, Paulin C, Revol A
European journal of endocrinology / European Federation of Endocrine Societies. 1998 ; 139 (2) : 209-216.
PMID 9724079
 
Low-frequency mutation of Ha-ras and Ki-ras oncogenes in transitional cell carcinoma of the bladder.
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Anticancer research. 1998 ; 18 (4A) : 2675-2678.
PMID 9703927
 
Mutations of ras genes are relatively frequent in Japanese prostate cancers: pointing to genetic differences between populations.
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PMID 9713462
 
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Contributor(s)

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 and Lion T . HRAS (Harvey rat sarcoma viral oncogene homolog). Atlas Genet Cytogenet Oncol Haematol. February 1999 .
URL : http://AtlasGeneticsOncology.org/Genes/HRASID108.html

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