HRAS
Available structures PDB Ortholog search:PDBeRCSB List of PDB id codes 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,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,421P,4DLR,4DLS,4DLT,4DLU,4DLV,4DLW,4DLX,4DLY,4DLZ,4EFL,4EFM,4EFN,4G0N,4G3X,4K81,4Q21,521P,5P21,621P,6Q21,721P,821P,4L9S,4L9W,4NYI,4NYJ,4NYM,4URU,4URV,4URW,4URX,4URY,4URZ,4US0,4US1,4US2,2N42,2N46,4XVQ,4XVR,4RSG,5B30
Identifiers
Aliases	HRAS, C-BAS/HAS, C-H-RAS, C-HA-RAS1, CTLO, H-RASIDX, HAMSV, HRAS1, RASH1, p21ras, Harvey rat sarcoma viral oncogene homolog, HRas proto-oncogene, GTPase, RASK2
External IDs	OMIM:190020;MGI:96224;HomoloGene:55890;GeneCards:HRAS;OMA:HRAS - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p15.5 Start 532,242bp[1] End 537,321bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 F5|7 86.48 cM Start 140,769,018bp[2] End 140,773,918bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of abdomen skin of leg putamen caudate nucleus nucleus accumbens Hypothalamus Temporal Lobe Amygdala right hemisphere of cerebellum substantia nigra Top expressed in dentate gyrus of hippocampal formation granule cell lip molar superior frontal gyrus esophagus fetal liver hematopoietic progenitor cell yolk sac entorhinal cortex perirhinal cortex muscle of thigh More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding protein C-terminus binding protein binding GTPase activity GTP binding GDP binding Cellular component cytoplasm cytosol Golgi apparatus intracellular membrane-bounded organelle membrane Golgi membrane plasma membrane perinuclear region of cytoplasm nucleus glutamatergic synapse Biological process negative regulation of neuron apoptotic process defense response to protozoan positive regulation of protein phosphorylation regulation of long-term neuronal synaptic plasticity endocytosis positive regulation of MAP kinase activity positive regulation of miRNA metabolic process positive regulation of epithelial cell proliferation positive regulation of ruffle assembly mitotic cell cycle checkpoint signaling positive regulation of cell migration ephrin receptor signaling pathway positive regulation of wound healing positive regulation of Ras protein signal transduction positive regulation of interferon-gamma production stimulatory C-type lectin receptor signaling pathway positive regulation of JNK cascade negative regulation of gene expression MAPK cascade intrinsic apoptotic signaling pathway positive regulation of GTPase activity chemotaxis cell surface receptor signaling pathway positive regulation of gene expression negative regulation of GTPase activity positive regulation of cell population proliferation positive regulation of ERK1 and ERK2 cascade animal organ morphogenesis T-helper 1 type immune response Ras protein signal transduction cell population proliferation T cell receptor signaling pathway positive regulation of actin cytoskeleton reorganization positive regulation of MAPK cascade negative regulation of cell population proliferation positive regulation of transcription by RNA polymerase II signal transduction apoptotic process small GTPase mediated signal transduction cellular senescence response to isolation stress cellular response to gamma radiation positive regulation of DNA replication positive regulation of phospholipase C activity protein heterooligomerization positive regulation of protein targeting to membrane regulation of neurotransmitter receptor localization to postsynaptic specialization membrane Sources:Amigo /QuickGO
Orthologs Species Human Mouse Entrez 3265 15461 Ensembl ENSG00000276536 ENSG00000174775 ENSMUSG00000025499 UniProt P01112 Q61411 RefSeq (mRNA) NM_001130442 NM_005343 NM_176795 NM_001318054 NM_001130443 NM_001130444 NM_008284 RefSeq (protein) NP_001123914 NP_001304983 NP_005334 NP_789765 NP_001123915 NP_001123916 NP_032310 Location (UCSC) Chr 11: 0.53 – 0.54 Mb Chr 7: 140.77 – 140.77 Mb PubMed search [3] [4]
Wikidata
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GTPase HRas, from "Harvey Rat sarcoma virus", also known astransforming protein p21 is anenzyme that in humans is encoded by theHRASgene.^[5][6] TheHRAS gene is located on the short (p) arm ofchromosome 11 at position 15.5, frombase pair 522,241 to base pair 525,549.^[7] HRas is asmall G protein in theRas subfamily of theRas superfamily ofsmall GTPases. Once bound toGuanosine triphosphate, H-Ras will activate aRaf kinase likec-Raf, the next step in theMAPK/ERK pathway.

GTPase HRas is involved in regulating cell division in response togrowth factor stimulation.Growth factors act by binding cell surfacereceptors that span the cell's plasma membrane. Once activated, receptors stimulate signal transduction events in thecytoplasm, a process by which proteins and second messengers relay signals from outside the cell to the cell nucleus and instructs the cell to grow or divide. The HRAS protein is aGTPase and is an early player in many signal transduction pathways and is usually associated withcell membranes due to the presence of anisoprenyl group on itsC-terminus. HRAS acts as a molecular on/off switch, once it is turned on it recruits and activates proteins necessary for the propagation of the receptor's signal, such asc-Raf andPI 3-kinase. HRAS binds toGTP in the active state and possesses an intrinsic enzymatic activity that cleaves the terminal phosphate of this nucleotide converting it toGDP. Upon conversion of GTP to GDP, HRAS is turned off. The rate of conversion is usually slow but can be sped up dramatically by an accessory protein of the GTPase activating protein (GAP) class, for exampleRasGAP. In turn HRAS can bind to proteins of the Guanine Nucleotide Exchange Factor (GEF) class, for exampleSOS1, which forces the release of bound nucleotide. Subsequently, GTP present in thecytosol binds and HRAS-GTP dissociates from the GEF, resulting in HRAS activation. HRAS is in theRas family, which also includes two other proto-oncogenes:KRAS andNRAS. These proteins all are regulated in the same manner and appear to differ largely in their sites of action within the cell.

At least five inheritedmutations in theHRAS gene have been identified in people withCostello syndrome. Each of these mutations changes an amino acid in a critical region of the HRAS protein. The most common mutation replaces theamino acidglycine with the amino acidserine at position 12 (written as Gly12Ser or G12S). The mutations responsible for Costello syndrome lead to the production of an HRAS protein that is permanently active. Instead of triggering cell growth in response to particular signals from outside the cell, the overactive protein directs cells to grow and divide constantly. This uncontrolled cell division can result in the formation of noncancerous and cancerous tumors. Researchers are uncertain how mutations in theHRAS gene cause the other features of Costello syndrome (such as mental retardation, distinctive facial features, and heart problems), but many of the signs and symptoms probably result from cell overgrowth and abnormal cell

HRAS has been shown to be aproto-oncogene. When mutated, proto-oncogenes have the potential to cause normal cells to becomecancerous. Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes are calledsomatic mutations and are not inherited. Somatic mutations in theHRAS gene in bladder cells have been associated withbladder cancer. One specific mutation has been identified in a significant percentage of bladder tumors; this mutation substitutes one protein building block (amino acid) for another amino acid in the HRAS protein. Specifically, the mutation replaces the amino acidglycine with the amino acidvaline at position 12 (written as Gly12Val, G12V, or H-RasV¹²). The altered HRAS protein is permanently activated within the cell. This overactive protein directs the cell to grow and divide in the absence of outside signals, leading to uncontrolled cell division and the formation of a tumor. Mutations in theHRAS gene also have been associated with the progression of bladder cancer and an increased risk of tumor recurrence after treatment.

Somatic mutations in theHRAS gene are probably involved in the development of several other types of cancer. These mutations lead to an HRAS protein that is always active and can direct cells to grow and divide without control. Recent studies suggest thatHRAS mutations are common in thyroid, salivary duct carcinoma,^[8] epithelial-myoepithelial carcinoma,^[9] and kidney cancers. DNA copy-number gain of a segment containingHRAS is included in a genome-wide pattern, which was found to be correlated with anastrocytoma patient's outcome.^[10][11]The HRAS protein also may be produced at higher levels (overexpressed) in other types of cancer cells.

• GeneReviews/NCBI/NIH/UW entry on Costello syndrome
• HRAS+protein,+human at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

• Genes on human chromosome 11
• Oncogenes

• Articles with short description
• Short description is different from Wikidata
• CS1: long volume value