GTPase KRas

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. Activates MAPK1/MAPK3 resulting in phosphorylation and ultimately degradation of GJA1 (By similarity). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner. 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 · 427

• 1D8D X-ray 2.00A
• 1D8E X-ray 3.00A
• 1KZO X-ray 2.20A
• 1KZP X-ray 2.10A
• 1N4P X-ray 2.65A
• 1N4Q X-ray 2.40A
• 1N4R X-ray 2.80A
• 1N4S X-ray 2.60A
• 2MSC NMR
• 2MSD NMR
• 2MSE NMR
• 3GFT X-ray 2.27A
• … and 415 more

A predicted model is available from AlphaFold.

Gene Ontology · 33

• GO:0005737 cytoplasm
• GO:0009898 cytoplasmic side of plasma membrane
• GO:0005829 cytosol
• GO:0005789 endoplasmic reticulum membrane
• GO:0005925 focal adhesion
• GO:0000139 Golgi membrane
• GO:0016020 membrane
• GO:0005741 mitochondrial outer membrane
• GO:0005886 plasma membrane
• GO:0003925 G protein activity
• GO:0019003 GDP binding
• GO:0019002 GMP binding
• GO:0005525 GTP binding
• GO:0003924 GTPase activity
• GO:0042802 identical protein binding
• GO:0030275 LRR domain binding
• GO:0044877 protein-containing complex binding
• GO:0043495 protein-membrane adaptor activity
• GO:0060038 cardiac muscle cell proliferation
• GO:0019221 cytokine-mediated signaling pathway
• GO:0007565 female pregnancy
• GO:0001889 liver development
• GO:0000165 MAPK cascade
• GO:0051450 myoblast proliferation
• GO:0008284 positive regulation of cell population proliferation
• GO:2000774 positive regulation of cellular senescence
• GO:0010628 positive regulation of gene expression
• GO:0046579 positive regulation of Ras protein signal transduction
• GO:0007265 Ras protein signal transduction
• GO:0051384 response to glucocorticoid
• GO:0009629 response to gravity
• GO:0035900 response to isolation stress
• GO:0051385 response to mineralocorticoid

Disease associations

• linear nevus sebaceous syndrome MONDO:0008097
• Toriello-Lacassie-Droste syndrome MONDO:0010854
• acute myeloid leukemia MONDO:0018874
• juvenile myelomonocytic leukemia MONDO:0011908
• Noonan syndrome 3 MONDO:0012371
• gastric cancer MONDO:0001056
• cardiofaciocutaneous syndrome 2 MONDO:0014112

Drugs targeting this protein · 3

• SALIRASIB inhibitor
• SOTORASIB inhibitor
• ADAGRASIB inhibitor

Related proteins · sequence + function similarity

• GTPase KRas 1.00
• GTPase KRas 1.00
• Ras-like protein 0.99
• GTPase NRas 0.98
• GTPase KRas 0.98
• GTPase HRas 0.98
• GTPase NRas 0.98
• GTPase NRas 0.98
• GTPase NRas 0.98
• GTPase NRas 0.98
• GTPase NRas 0.98
• GTPase NRas 0.98

Co-cited proteins · studied together in the literature

• GTPase NRas 9 shared papers
• 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid receptor 1 shared papers
• Ras-related protein R-Ras 2 shared papers
• GTPase HRas 8 shared papers
• Leucine-zipper-like transcriptional regulator 1 3 shared papers
• Ras-related protein M-Ras 6 shared papers
• Leucine-zipper-like transcriptional regulator 1 homolog 1 shared papers
• Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta 1 shared papers
• Target of rapamycin complex 2 subunit MAPKAP1 2 shared papers
• Serine/threonine-protein kinase B-raf 3 shared papers
• Leucine-rich repeat protein SHOC-2 5 shared papers
• Rap1 GTPase-GDP dissociation stimulator 1 2 shared papers

Literature · 59 cited papers

• Structural basis for LZTR1 recognition of RAS GTPases for degradation. Science · 2025
• The small GTPase MRAS is a broken switch. Nat. Commun. · 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
• Structural insights into Ras regulation by SIN1. Proc. Natl. Acad. Sci. U.S.A. · 2022
• KRAS A146 mutations are associated with distinct clinical behavior in patients with colorectal liver metastases. JCO Precis. Oncol. · 2021
• RAS interaction with Sin1 is dispensable for mTORC2 assembly and activity. Proc. Natl. Acad. Sci. U.S.A. · 2021
• Expansion of the phenotypic spectrum and description of molecular findings in a cohort of patients with oculocutaneous mosaic RASopathies. Mol. Genet. Genomic Med. · 2019
• LZTR1 is a regulator of RAS ubiquitination and signaling. Science · 2018
• Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination. Science · 2018
• … and 47 more in the literature graph