GTPase HRas
Also known as: HRAS, HRAS1
Function
Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival. Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Recognized by LZTR1 that mediates its ubiquitination by a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex.
Classification
- Family (Pfam)
- PF00071 Ras
- InterPro
- P-loop_NTPase, Small_GTP-bd, Small_GTPase, Small_GTPase_Ras-type
- Functional cluster
- Small GTPases (Ras/Rab) & related
Experimental structures · PDB · 235
- 121P X-ray 1.54A
- 1AA9 NMR
- 1AGP X-ray 2.30A
- 1BKD X-ray 2.80A
- 1CLU X-ray 1.70A
- 1CRP NMR
- 1CRQ NMR
- 1CRR NMR
- 1CTQ X-ray 1.26A
- 1GNP X-ray 2.70A
- 1GNQ X-ray 2.50A
- 1GNR X-ray 1.85A
- … and 223 more
A predicted model is available from AlphaFold.
Gene Ontology · 46
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005789 endoplasmic reticulum membrane
- GO:0098978 glutamatergic synapse
- GO:0005794 Golgi apparatus
- GO:0000139 Golgi membrane
- GO:0005654 nucleoplasm
- GO:0048471 perinuclear region of cytoplasm
- GO:0005886 plasma membrane
- GO:0003925 G protein activity
- GO:0019003 GDP binding
- GO:0005525 GTP binding
- GO:0003924 GTPase activity
- GO:0160185 phospholipase C activator activity
- GO:0043495 protein-membrane adaptor activity
- GO:0060612 adipose tissue development
- GO:0009887 animal organ morphogenesis
- GO:0007166 cell surface receptor signaling pathway
- GO:0071480 cellular response to gamma radiation
- GO:0090398 cellular senescence
- GO:0006935 chemotaxis
- GO:0008286 insulin receptor signaling pathway
- GO:0000165 MAPK cascade
- GO:0042552 myelination
- GO:0008285 negative regulation of cell population proliferation
- GO:0010629 negative regulation of gene expression
- GO:0030335 positive regulation of cell migration
- GO:0008284 positive regulation of cell population proliferation
- GO:0050679 positive regulation of epithelial cell proliferation
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:0046330 positive regulation of JNK cascade
- GO:0043410 positive regulation of MAPK cascade
- GO:2000630 positive regulation of miRNA metabolic process
- GO:0090314 positive regulation of protein targeting to membrane
- GO:0046579 positive regulation of Ras protein signal transduction
- GO:1900029 positive regulation of ruffle assembly
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0090303 positive regulation of wound healing
- GO:0007265 Ras protein signal transduction
- GO:0032956 regulation of actin cytoskeleton organization
- GO:0051726 regulation of cell cycle
- GO:0042127 regulation of cell population proliferation
- GO:0098696 regulation of neurotransmitter receptor localization to postsynaptic specialization membrane
- GO:0006357 regulation of transcription by RNA polymerase II
- GO:0014044 Schwann cell development
- GO:0007165 signal transduction
Disease associations
- urinary bladder cancer MONDO:0001187
- linear nevus sebaceous syndrome MONDO:0008097
- thyroid cancer, nonmedullary, 2 MONDO:0008566
- Costello syndrome MONDO:0009026
Drugs targeting this protein · 1
- SALIRASIB inhibitor
Related proteins · sequence + function similarity
- GTPase HRas 1.00
- GTPase HRas 1.00
- GTPase HRas 1.00
- GTPase HRas 1.00
- GTPase HRas 0.99
- GTPase NRas 0.99
- GTPase NRas 0.99
- GTPase NRas 0.99
- GTPase NRas 0.99
- GTPase NRas 0.99
- GTPase NRas 0.99
- GTPase NRas 0.98
Co-cited proteins · studied together in the literature
- GTPase NRas 11 shared papers
- Carabin 1 shared papers
- Ras association domain-containing protein 5 1 shared papers
- Cytotoxin-L 4 shared papers
- Zinc finger protein Aiolos 1 shared papers
- GTPase KRas 8 shared papers
- Ras GTPase-activating protein 1 1 shared papers
- ADP-ribosylation factor-like protein 2 1 shared papers
- Golgin subfamily A member 7 1 shared papers
- GTPase HRas 1 shared papers
- Ras-related protein M-Ras 4 shared papers
- Rap guanine nucleotide exchange factor 2 2 shared papers
Literature · 60 cited papers
- Structural basis for LZTR1 recognition of RAS GTPases for degradation. Science · 2025
- Structure of the SHOC2-MRAS-PP1c complex provides insights into RAF activation and Noonan syndrome. Nat. Struct. Mol. Biol. · 2022
- Structure-function analysis of the SHOC2-MRAS-PP1c holophosphatase complex. Nature · 2022
- Structural basis for SHOC2 modulation of RAS signalling. Nature · 2022
- Structural insights into Ras regulation by SIN1. Proc. Natl. Acad. Sci. U.S.A. · 2022
- Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination. Science · 2018
- SIRT2 and lysine fatty acylation regulate the transforming activity of K-Ras4a. Elife · 2017
- A novel HRAS substitution (c.266C>G; p.S89C) resulting in decreased downstream signaling suggests a new dimension of RAS pathway dysregulation in human development. Am. J. Med. Genet. A · 2012
- Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome. Nat. Genet. · 2012
- Duplication of Glu37 in the switch I region of HRAS impairs effector/GAP binding and underlies Costello syndrome by promoting enhanced growth factor-dependent MAPK and AKT activation. Hum. Mol. Genet. · 2010
- Distinct kinetics of (H/K/N)Ras glucosylation and Rac1 glucosylation catalysed by Clostridium sordellii lethal toxin. FEBS Lett. · 2009
- Human protein factory for converting the transcriptome into an in vitro-expressed proteome. Nat. Methods · 2008
- … and 48 more in the literature graph
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