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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005343 6 - 1061 NP_005334 21 189 - 2012 22707223 NM_176795 7 - 1251 NP_789765 - 170 - 2012 22707223 NM_001130442 5 - 1169 NP_001123914 21 189 - 2012 22707223

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       moderately Digestive mouth tongue     highly   salivary gland       highly Nervous brain       moderately Respiratory lung       moderately Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone     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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer urinary   abnormal methylation of the HRAS gene may be further used as a potential therapeutic target

ANIMAL & CELL MODELS