CODSWALLOP

GTPase KRas

Homo sapiens · seed P01116 · 189 aa · family defined as ≥30% identity to that seed · compiled 09 August 2026

1,445Entries
1,494Polymer entities
706Distinct constructs
26Organisms
1,405Ligand-bound
0.95 ÅBest resolution
1.92 ÅMedian resolution

Every figure here is counted over the whole family rather than quoted from one entry.

Constructs, most-used first

706 distinct constructs across 1,445 entries. 1,286 polymer entities differ from the UniProt canonical sequence in some way, 107 carry a recognised expression tag and 0 carry a fusion partner.

"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.

EntitiesLengthBest (Å)Best entryWhat was made
62 166 1.26 1CTQ residues 1-166
58 185 1.31 7G83 residues 1-184
42 170 1.16 6TAN residues 1-169; G12C, C51S, C80L +7 more
35 167 1.20 8TBG residues 1-166
26 167 1.65 6V9M residues 1-166; Y64A
25 170 1.16 8R7W residues 1-169; G12D, R151G, E153D +4 more
15 167 1.67 4HDO residues 1-167
15 170 1.24 4OBE residues 1-169; R151G, E153D, Q165K +3 more
13 178 1.48 9HU8 residues 1-177
12 170 0.95 9IAY residues 1-169; C118S, R151G, E153D +4 more
12 172 1.14 9G4B residues 1-169; C118S
11 169 residues 1-169; G12V, C118S, R151G +5 more
10 170 1.15 4LDJ residues 1-169; G12C, R151G, E153D +4 more
10 170 1.27 7RT1 residues 1-169; G12D, C51S, C80L +7 more
9 170 1.04 8AZX residues 1-169; G12C, C118S, R151G +5 more
9 183 1.50 6PGP His7; residues 1-169; G12C, C51S, C80L +7 more
9 185 2.17 4US0 His6; TEV site; residues 1-166
9 186 1.18 6P0I residues 1-187; 1 internal deletion; M180L, D182H, S183H +4 more
9 189 2.61 9NI4 1 internal deletion; R151G, E153D, Q165K +15 more
8 166 1.30 3OIW residues 1-166; G12V
8 169 1.49 6MS9 residues 1-169; R151G, E153D, Q165K +3 more
8 170 1.02 8AZZ residues 1-169; G12V, C118S, R151G +5 more
8 170 1.09 8AZY residues 1-169; G12D, C118S, R151G +5 more
8 177 1.34 9IFK residues 1-177
8 193 1.75 6R3V matches the canonical sequence

Showing the 25 most-used of 706.

Positions people deliberately mutate

Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".

E153D 68% H95Q 63% K128E 62% P121A 60% S122A 60% Q165K 60% D126E 59% T127S 57% E107D 54% C118S 54% C80L 50% C51V 50% T87P 46% H94E 46% F141Y 45% G12S 45% L52K 45% A83S 45% L23F 44% H27Q 44% N85T 44% A11D 44% T124P 44% I24T 44% Q70L 44% T2I 43% Q150D 43% D154E 43% E76D 43% R149K 43%

What it assembles into

Oligomeric stateChainsEntriesShare
monomeric1 710 49.1%
dimeric2 506 35.0%
trimeric3 110 7.6%
tetrameric4 75 5.2%
hexameric6 15 1.0%
pentameric5 9 0.6%
octameric8 8 0.6%
heptameric7 4 0.3%

777 entries have the depositor's assembly corroborated by PISA, 627 carry the depositor's word alone and 41 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 70 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1DOA, 1FOE, 1NF3, 1NVU, 1NVV, 1NVW, 1S8F, 1TU4, 1YU9, 1Z08, 1Z0A, 1ZBD, 2ATX, 2DFK, 2IEY, 2IEZ, 2IF0, 2IL1, 2NZJ, 2OCY.

Domain architecture

DomainSourceSpan (seed)Chains
P-loop containing nucleotide triphosphate hydrolasesCATH 3.40.50.300 4–171 950
Ras-like P-loop GTPasesSCOP2B 8019405 1–166 223
Ras-like P-loop GTPasesSCOP2B 8057488 1–167 16
Ras-like P-loop GTPasesSCOP2B 8060856 2–165 462
Ras-like P-loop GTPasesSCOP2B 8057492 2–168 21
Ras-like P-loop GTPasesSCOP2B 8057406 3–178 49
Ras-like P-loop GTPasesSCOP2B 8057416 3–184 44
Ras-like P-loop GTPasesSCOP2B 8054292 4–171 16
Ras-like P-loop GTPasesSCOP2B 8057414 9–185 121
Ras-like P-loop GTPasesSCOP2B 8089844 11–179 19
Ras-like P-loop GTPasesSCOP2B 8057254 12–178 28
Ras-like P-loop GTPasesSCOP2B 8057282 15–183 16

What binds it

ComponentClassNameEntriesBest (Å)
MGion Magnesium Ion 1,125 0.95
GDPcofactor Guanosine-5'-Diphosphate 615 0.95
GNPcofactor Phosphoaminophosphonic Acid-Guanylate Ester 455 1.00
GOLcryoprotectant Glycerol 130 1.05
CAion Calcium Ion 122 1.18
GTPcofactor Guanosine-5'-Triphosphate 97 1.19
EDOcryoprotectant 1,2-Ethanediol 96 0.95
FMTbuffer Formic Acid 89 1.31
SO4ion Sulfate Ion 86 1.12
DMScryoprotectant Dimethyl Sulfoxide 65 1.31
CLion Chloride Ion 57 1.08
GSPcofactor 5'-Guanosine-Diphosphate-Monothiophosphate 49 1.40
NAion Sodium Ion 44 1.18
GCPligand Phosphomethylphosphonic Acid Guanylate Ester 37 1.12
ZNion Zinc Ion 37 1.81
PO4ion Phosphate Ion 35 1.60
ACTcryoprotectant Acetate Ion 29 1.18
AF3ligand Aluminum Fluoride 21 1.42
PEGcryoprotectant Di(Hydroxyethyl)ether 21 1.01
6ICligand 4-(4-[(1r,5s)-3,8-Diazabicyclo[3.2.1]octan-3-Yl]-8-Fluoro-2-{[(2 19 1.23

How it crystallises

Parsed from the free text 1,274 depositors typed into _exptl_crystal_grow.pdbx_details, out of 1,290 entries that recorded anything at all. Median pH 7.0 (range 1.0 to 10.5).

Precipitants

PEG × Magnesium chloride × Sodium chloride × Ammonium sulfate × Sodium formate × Calcium chloride × Sodium citrate × Lithium sulfate × MPD × Isopropanol × PEG (unspecified) × Sodium malonate × Dioxane × Tacsimate ×

Buffers

Tris × Sodium acetate × MES × Citrate × HEPES × Bis-Tris × Sodium cacodylate × Phosphate × Imidazole × Bis-Tris propane × Glycine × CHES ×

Which entries to trust

1,445 entries carry a wwPDB validation report: 613 clean, 574 worth a check and 258 with something to explain. Median clashscore 4.68, median RSRZ outliers 4.25%, median R-free minus R-work 0.037. 1,391 have released structure factors.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Homo sapiens1,313 0.95 1291 100%
Mus musculus35 1.20 34 96%
Saccharomyces cerevisiae20 1.35 12 100%
Rattus norvegicus15 1.00 15 96%
Arabidopsis thaliana12 1.53 10 94%
Saccharomyces cerevisiae S288C9 1.70 7 86%
Hordeum vulgare5 1.33 5 93%
Drosophila melanogaster5 1.39 3 87%
Leishmania donovani4 1.80 3 84%
Saguinus oedipus3 1.50 3 85%
Candidatus Thorarchaeota archaeon SMTZ1-453 1.50 3 84%
Avena sativa3 1.60 3 84%

Seed sequence

189 residues. Every identity figure in this document is measured against this sequence.

MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQRVEDAFYTLVREIRQYRLKKISKEEKTPGCVKIKKCIIM

Primary citations

One record per paper, not per entry.

YearCitation
2026 Expanding Addressable KRAS Mutations through the Structure- and Property-Based Design of Dual-State (GDP/GTP), Reversible Pan-KRAS Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.6c01325
2026 Selective Inhibition of KRASG13C Reveals an Increased Dependence on Wild-Type RAS Isoforms in Codon 13 RAS-Mutant Cancers. Cancer Discov doi:10.1158/2159-8290.CD-25-0886
2026 From KRAS G12D to Pan-KRAS Inhibitors─A Journey Enabled by Synthetic Innovation and Structure-Based Drug Design. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03662
2026 Nucleotide-dependent switching and RIPb effector recognition of the barley susceptibility factor RACB. Commun Biol doi:10.1038/s42003-026-10316-7
2026 Discovery of BBO-11818, a Potent and Selective Noncovalent Inhibitor of (ON) and (OFF) KRAS with Activity against Multiple Oncogenic Mutants. Cancer Discov doi:10.1158/2159-8290.CD-25-1280
2026 Structure of SHOC2-KRAS-PP1C complex reveals RAS isoform-specific determinants and insights into targeting complex assembly by RAS inhibitors. Nat Commun doi:10.1038/s41467-026-68319-1
2026 Targeting the H/KRAS alpha 4-beta 6-alpha 5 Allosteric Lobe with Macrocyclic Peptides. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.6c00078
2026 Discovering Targetable Conformation of RhoA Mutant by Integrating Native Mass Spectrometry, Ultraviolet Photodissociation, and X-ray Diffraction. J.Am.Chem.Soc. doi:10.1021/jacs.5c20067
2026 Optimization of Covalent Warhead Trajectory for KRAS G12C Active-State Inhibition. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03306
2026 Optimization of Covalent 6-Cyanoquinazoline KRAS G12C Inhibitors for the Treatment of Solid Tumors. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03610
2026 Systematic cysteine scanning identifies a druggable pocket in oncogenic KRAS. Cell Chem Biol doi:10.1016/j.chembiol.2026.01.007
2026 Covalent inhibitor design confers activity against both GDP- and GTP-bound forms of KRAS G12C. Nat Commun doi:10.1038/s41467-026-69003-0
2026 Structure-Guided Development of NRAS G12D Inhibitors Based on a 5‐Azaindole Core. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.5c00647
2026 Disrupted molecular glue complex drives RAS inhibitor resistance. Cell doi:10.1016/j.cell.2026.03.031
2026 Targeting Multiple KRAS Mutations with High-Affinity Macrocyclic Inhibitors: From Discovery to Preclinical Validation. J.Med.Chem. doi:10.1021/acs.jmedchem.6c00127
2026 Structure-Activity Relationship Analysis of Macrocyclic Peptide RAS Inhibitors: Spotlight on the Solvent-Exposed Region. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.6c00122
2026 Analysis of structure and stability of Leishmania donovani Rab5a and Rab5b. Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2026.152349
2026 The cytokinesis regulator RacGAP1 is a Rac1-specific GAP on membranes. Protein Sci. doi:10.1002/pro.70488
2026 Discovery and Characterization of Divarasib (GDC-6036), a Potent Covalent Inhibitor of KRAS G12C. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02272
2026 Discovery and Optimization of a Potent, Efficacious, and Brain-Penetrant Inhibitor of KRAS G12C. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02279
2026 An evolutionarily conserved salt bridge stabilizes the active site for GTP hydrolysis in Rho GTPases. J.Biol.Chem. doi:10.1016/j.jbc.2026.111260
2026 Structures of the PI3K alpha /KRas complex on lipid bilayers reveal molecular mechanisms of PI3K alpha activation. Mol.Cell doi:10.1016/j.molcel.2026.06.010
2026 Structural basis of fungal beta-1,3-glucan synthase inhibition by caspofungin. Nature doi:10.1038/s41586-026-10409-7
2026 A novel RAB5 binding site in human VPS34-CII that is likely the primordial site in eukaryotic evolution. Elife doi:10.7554/eLife.110040
2026 Protein Engineering-Enabled Cryo-EM Investigation of Small GTPases. J.Mol.Biol. doi:10.1016/j.jmb.2026.169860
2026 Cyclized Peptide Inhibitors of the Small G Protein Cdc42 Mimic Binding of Effector Proteins. Biochemistry doi:10.1021/acs.biochem.5c00616
2025 Discovery of BI-2493, a Pan-KRAS Inhibitor Showing In Vivo Efficacy. J.Med.Chem. doi:10.1021/acs.jmedchem.5c00576
2025 Revealing Functional Hotspots: Temperature-Dependent Crystallography of K-RAS Highlights Allosteric and Druggable Sites. Biorxiv doi:10.1101/2025.02.27.639303
2025 A neomorphic protein interface catalyzes covalent inhibition of RAS G12D aspartic acid in tumors. Science doi:10.1126/science.ads0239
2025 Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers. J.Med.Chem. doi:10.1021/acs.jmedchem.4c02314
2025 Reversible Small Molecule Multivariant Ras Inhibitors Display Tunable Affinity for the Active and Inactive Forms of Ras. J.Med.Chem. doi:10.1021/acs.jmedchem.4c02929
2025 Identification of Structurally Novel KRAS G12C Inhibitors through Covalent DNA-Encoded Library Screening. J.Med.Chem. doi:10.1021/acs.jmedchem.4c03071
2025 Discovery of Elironrasib (RMC-6291), a Potent and Orally Bioavailable, RAS(ON) G12C-Selective, Covalent Tricomplex Inhibitor for the Treatment of Patients with RAS G12C-Addicted Cancers. J.Med.Chem. doi:10.1021/acs.jmedchem.4c02313
2025 Hierarchical folding-upon-binding of an intrinsically disordered protein. Nat Commun doi:10.1038/s41467-025-66420-5
2025 Design, Structure Optimization, and Preclinical Characterization of JAB-21822, a Covalent Inhibitor of KRAS G12C. J.Med.Chem. doi:10.1021/acs.jmedchem.4c02939
2025 Promise and Challenge of beta-Lactone Electrophiles to Target Aspartate 12 of Mutant KRAS G12D . J.Med.Chem. doi:10.1021/acs.jmedchem.5c01214
2025 Discovery of INCB159020, an Orally Bioavailable KRAS G12D Inhibitor. J.Med.Chem. doi:10.1021/acs.jmedchem.4c02662
2025 Discovery of KRAS(G12D) selective degrader ASP3082. Commun Chem doi:10.1038/s42004-025-01662-4
2025 Structural insights into isoform-specific RAS-PI3K alpha interactions and the role of RAS in PI3K alpha activation. Nat Commun doi:10.1038/s41467-024-55766-x
2025 Small-Molecule KRAS Inhibitors by Tyrosine Covalent Bond Formation. Chemmedchem doi:10.1002/cmdc.202400624