Tchem HRAS GTPase HRas

Protein Summary

Description

Involved in the activation of Ras protein signal transduction (PubMed:22821884). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:12740440, PubMed:14500341, PubMed:9020151). This gene belongs to the Ras oncogene family, whose members are related to the transforming genes of mammalian sarcoma retroviruses. The products encoded by these genes function in signal transduction pathways. These proteins can bind GTP and GDP, and they have intrinsic GTPase activity. This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus. Mutations in this gene cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, cognitive disability, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Defects in this gene are implicated in a variety of cancers, including bladder cancer, follicular thyroid cancer, and oral squamous cell carcinoma. Multiple transcript variants, which encode different isoforms, have been identified for this gene. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P01112
• B5BUA0
• Q14080
• Q6FHV9
• Q9BR65
• Q9UCE2

Gene Name

• HRAS

Ensembl ID

• ENST00000311189
• ENSP00000309845
• ENSG00000174775
• ENST00000397594
• ENSP00000380722
• ENST00000397596
• ENSP00000380723
• ENST00000417302
• ENSP00000388246
• ENST00000451590
• ENSP00000407586
• ENST00000493230
• ENSP00000434023
• ENST00000610977
• ENSP00000480686
• ENSG00000276536
• ENST00000615062
• ENSP00000482366
• ENST00000616241
• ENSP00000480317
• ENST00000631404
• ENSP00000488757
• ENST00000631967
• ENSP00000488225
• ENST00000634098
• ENSP00000488296

Symbol

• HRAS1
• CTLO
• KRAS
• HAMSV
• HRAS1
• KRAS2
• RASH1
• RASK2
• Ki-Ras
• p21ras
• C-H-RAS
• c-K-ras
• H-RASIDX
• c-Ki-ras
• C-BAS/HAS
• C-HA-RAS1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
pathway	1
chemical	0.99
hub protein	0.99
phenotype	0.94

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / G-protein / Small Gtpase / Gtpase Hras

DTO Classes

Protein / Enzyme Modulator / G-protein / Small Gtpase / Gtpase Hras

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 13112.46   (req: < 5)

Gene RIFs: 463   (req: <= 3)

Antibodies: 683   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 13112.46   (req: >= 5)

Gene RIFs: 463   (req: > 3)

Antibodies: 683   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 49

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 19

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2

Protein Sequence and Structure

Residue Counts

Protein Sequence

Find Targets by Sequence

Show Full Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (2)

Explore Approved Drugs

1 – 2 of 2

lonafarnib

HRASTchem Enzyme

INHIBITOR pIC50 : 8.55

stallimycin

HRASTchem Enzyme

pIC50 : 6.7

Active Ligands (19)

Explore Active Ligands

1 – 10 of 19

CHEMBL554247

HRASTchem Enzyme

pIC50 : 7.82

CHEMBL552690

HRASTchem Enzyme

pIC50 : 7.82

CHEMBL554353

HRASTchem Enzyme

pIC50 : 7.82

CHEMBL540313

HRASTchem Enzyme

pIC50 : 7.82

CHEMBL554189

HRASTchem Enzyme

pIC50 : 7.82

CHEMBL552863

HRASTchem Enzyme

pIC50 : 7.7

CHEMBL536328

HRASTchem Enzyme

pIC50 : 7.7

CHEMBL4456044

HRASTchem Enzyme

pKd : 7.29

CHEMBL326352

HRASTchem Enzyme

pIC50 : 7.06

CHEMBL407445

HRASTchem Enzyme

pIC50 : 6.75

Protein-Protein Interactions (1037)

Explore Interacting Targets

1 – 10 of 1037

• See Interactions on String-DB

RIN1

Tbio

Novelty:  0.02401084

p_int:  0.999920775

p_ni:  0.000079225

Score:  0.964

Data Source:  BioPlex,STRINGDB

BRAF

Tclin

Family:  Kinase

Novelty:  0.00253795

p_int:  0.998682404

p_ni:  0.001317591

p_wrong:  5e-9

Score:  0.997

Data Source:  BioPlex,Reactome,STRINGDB

RABGGTB

Tbio

Family:  Enzyme

Novelty:  0.06786314

p_int:  0.994792299

p_ni:  0.005207631

p_wrong:  7e-8

Score:  0.263

Data Source:  BioPlex,STRINGDB

RGL1

Tbio

Novelty:  0.0095933

p_int:  0.992532424

p_ni:  0.007165967

p_wrong:  0.000301609

Score:  0.948

Data Source:  BioPlex,STRINGDB

TMEM185A

Tdark

Novelty:  0.0262898

p_int:  0.992224121

p_ni:  0.007775844

p_wrong:  3.5e-8

Score:  0.285

Data Source:  BioPlex,STRINGDB

CYP2S1

Tbio

Novelty:  0.02967417

p_int:  0.989422085

p_ni:  0.010577901

p_wrong:  1.4e-8

Score:  0.295

Data Source:  BioPlex,STRINGDB

DUSP22

Tbio

Family:  Enzyme

Novelty:  0.01579003

p_int:  0.981653786

p_ni:  0.018345936

p_wrong:  2.77e-7

Score:  0.261

Data Source:  BioPlex,STRINGDB

SLC25A41

Tdark

Family:  Transporter

Novelty:  1.04918395

p_int:  0.977822329

p_ni:  0.015359264

p_wrong:  0.006818408

Data Source:  BioPlex

ATG3

Tbio

Novelty:  0.00541077

p_int:  0.977406914

p_ni:  0.020816048

p_wrong:  0.001777038

Score:  0.32

Data Source:  BioPlex,STRINGDB

VDAC3

Tbio

Novelty:  0.0095068

p_int:  0.977028169

p_ni:  0.022970652

p_wrong:  0.000001179

Score:  0.459

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (25)

Explore Nearest Tclin Targets

Upstream (20)

Downstream (5)

1 – 5 of 20

EGFR

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  37

1: PI3K-Akt signaling pathway

2: Central carbon metabolism in cancer

3: EGFR tyrosine kinase inhibitor resistance

4: Endocrine resistance

more:  33 more common pathways

KIT

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  10

1: PI3K-Akt signaling pathway

2: Central carbon metabolism in cancer

3: Acute myeloid leukemia

4: Breast cancer

more:  6 more common pathways

FGFR1

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  13

1: PI3K-Akt signaling pathway

2: Central carbon metabolism in cancer

3: Melanoma

4: Breast cancer

more:  9 more common pathways

PDGFRA

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  19

1: PI3K-Akt signaling pathway

2: Central carbon metabolism in cancer

3: EGFR tyrosine kinase inhibitor resistance

4: Focal adhesion

more:  15 more common pathways

IGF1R

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  22

1: PI3K-Akt signaling pathway

2: EGFR tyrosine kinase inhibitor resistance

3: Endocrine resistance

4: Focal adhesion

more:  18 more common pathways

Pathways (334)

Reactome (126)

KEGG (77)

PathwayCommons (72)

WikiPathways (59)

Activated NTRK2 signals through FRS2 and FRS3 (R-HSA-9028731)

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Items per page:

5

1 – 5 of 126

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activated NTRK2 signals through FRS2 and FRS3	11 targets	R-HSA-9028731
Reactome	Activated NTRK2 signals through RAS	9 targets	R-HSA-9026519
Reactome	Activated NTRK3 signals through RAS	8 targets	R-HSA-9034864
Reactome	Activation of NMDA receptors and postsynaptic events	74 targets	R-HSA-442755
Reactome	Activation of RAS in B cells	5 targets	R-HSA-1169092

Name	Explore in Pharos	Explore in Source
Activated NTRK2 signals through FRS2 and FRS3	11 targets	R-HSA-9028731
Activated NTRK2 signals through RAS	9 targets	R-HSA-9026519
Activated NTRK3 signals through RAS	8 targets	R-HSA-9034864
Activation of NMDA receptors and postsynaptic events	74 targets	R-HSA-442755
Activation of RAS in B cells	5 targets	R-HSA-1169092

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (57)

Functions (4)

Components (8)

Processes (45)

Find Similar Targets

Items per page:

10

1 – 4 of 4

GO Term	Evidence	Assigned by
GTP binding	Inferred from Direct Assay (IDA)	UniProtKB
GTPase activity	Inferred from Direct Assay (IDA)	WormBase
protein C-terminus binding	Inferred from Physical Interaction (IPI)	UniProtKB
GDP binding	Inferred from Mutant Phenotype (IMP)	CAFA

Disease Associations ()

No disease associations found

GWAS Traits (6)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 6

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
systemic lupus erythematosus	EFO_0002690	8	7	0	1.2	91.3
reticulocyte measurement	EFO_0010700	2	2	2		64.4
systemic scleroderma	EFO_0000717	2	2	0	1.2	46.9
reticulocyte count	EFO_0007986	1	1	1		11.2
myositis	EFO_0000783	1	1	0	1.1	9.6

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 6

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
systemic lupus erythematosus	EFO_0002690	0	1.2	91.3
reticulocyte measurement	EFO_0010700	2		64.4
systemic scleroderma	EFO_0000717	0	1.2	46.9
reticulocyte count	EFO_0007986	1		11.2
myositis	EFO_0000783	0	1.1	9.6

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Golgi apparatus
GTP-binding

GWAS Trait Find Similar Targets

No Header	No Header
myositis
reticulocyte count
reticulocyte measurement
rheumatoid arthritis
systemic lupus erythematosus
systemic scleroderma

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype

IDG Resources

No IDG generated resources found

Orthologs (8)

1 – 5 of 8

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	HRas proto-oncogene, GTPase	VGNC:50562	466302
Macaque	HRas proto-oncogene, GTPase		698830
Mouse	Harvey rat sarcoma virus oncogene	MGI:96224	15461
Rat	HRas proto-oncogene, GTPase	RGD:2827	293621
Horse	HRas proto-oncogene, GTPase	VGNC:18868	100055481

Species	Name	OMA	EggNOG	Inparanoid
Chimp	HRas proto-oncogene, GTPase
Macaque	HRas proto-oncogene, GTPase
Mouse	Harvey rat sarcoma virus oncogene
Rat	HRas proto-oncogene, GTPase
Horse	HRas proto-oncogene, GTPase

Publication Statistics

PubMed Score 13112.46

PubMed score by year

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PubTator Score 1772.19

PubTator score by year

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Related Publications

Text Mined References (666)

GeneRif Annotations (463)

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10

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PMID	Year	Title