GTPase NRas

UniProt P01111 Organism Homo sapiens Gene HRAS1, NRAS EC 3.6.5.2

Also known as: HRAS1, NRAS

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 · 29

2N9C NMR
3CON X-ray 1.65A
5UHV X-ray 1.67A
6E6H X-ray 1.99A
6MPP NMR
6ULI X-ray 1.88A
6ULK X-ray 1.90A
6ULN X-ray 2.01A
6ULR X-ray 3.20A
6UON X-ray 3.50A
6WGH X-ray 1.65A
6ZIO X-ray 1.55A
… and 17 more

A predicted model is available from AlphaFold.

Gene Ontology · 17

Disease associations

large congenital melanocytic nevus MONDO:0044792
nevus, epidermal MONDO:0008093
thyroid cancer, nonmedullary, 2 MONDO:0008566
neurocutaneous melanocytosis MONDO:0009578
juvenile myelomonocytic leukemia MONDO:0011908
Noonan syndrome 6 MONDO:0013186
autoimmune lymphoproliferative syndrome type 4 MONDO:0013767

Drugs targeting this protein · 1

SALIRASIB inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

GTPase HRas 11 shared papers
GTPase KRas 9 shared papers
Ras association domain-containing protein 7 1 shared papers
Winged helix repair factor 1 1 shared papers
Ras-related protein M-Ras 5 shared papers
Alpha/beta hydrolase domain-containing protein 17A 1 shared papers
Alpha/beta hydrolase domain-containing protein 17B 1 shared papers
Alpha/beta hydrolase domain-containing protein 17C 1 shared papers
Golgin subfamily A member 7 1 shared papers
Leucine-rich repeat protein SHOC-2 4 shared papers
Leucine-zipper-like transcriptional regulator 1 1 shared papers
Leucine-zipper-like transcriptional regulator 1 2 shared papers

Literature · 34 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
Structure of the MRAS-SHOC2-PP1C phosphatase complex. Nature · 2022
Structural basis for SHOC2 modulation of RAS signalling. Nature · 2022
Pharmacological targeting of STK19 inhibits oncogenic NRAS-driven melanomagenesis. Cell · 2019
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
ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization. Elife · 2015
N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS. J. Invest. Dermatol. · 2013
Keratinocytic epidermal nevi are associated with mosaic RAS mutations. J. Med. Genet. · 2012
… and 22 more in the literature graph

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