K-Ras

Gtpase kras

Reviewed UniProt entries for K-Ras and its protein partners


UniProt code UniProt Name Protein Name Gene Name Organism Length
Q9YH38 RASK_CYPCA GTPase KRas (Ki-Ras) (K-ras) kras Cyprinus carpio (Common carp) 188
P01116 RASK_HUMAN GTPase KRas (K-Ras 2) (Ki-Ras) (c-K-ras) (c-Ki-ras) [Cleaved into: GTPase KRas; N-terminally processed] KRAS KRAS2 RASK2 Homo sapiens (Human) 189
Q5EFX7 RASK_KRYMA GTPase KRas (Ki-Ras) (K-ras) kras Kryptolebias marmoratus (Mangrove killifish) (Rivulus marmoratus) 188
P79800 RASK_MELGA GTPase KRas (K-Ras 2) (Ki-Ras) (K-ras) KRAS Meleagris gallopavo (Common turkey) 188
Q07983 RASK_MONDO GTPase KRas (K-Ras 2) (Ki-Ras) (c-K-ras) (c-Ki-ras) [Cleaved into: GTPase KRas; N-terminally processed] KRAS Monodelphis domestica (Gray short-tailed opossum) 188
P32883 RASK_MOUSE GTPase KRas (K-Ras 2) (Ki-Ras) (c-K-ras) (c-Ki-ras) [Cleaved into: GTPase KRas; N-terminally processed] Kras Kras2 Mus musculus (Mouse) 189
P01117 RASK_MSVKI GTPase KRas (Ki-Ras) (Transforming protein p21/K-Ras) K-RAS KIS Kirsten murine sarcoma virus 189
O42277 RASK_ORYLA GTPase KRas (Ki-Ras) (K-ras) kras1 Oryzias latipes (Medaka fish) (Japanese ricefish) 188
P08644 RASK_RAT GTPase KRas (K-Ras 2) (Ki-Ras) (c-K-ras) (c-Ki-ras) [Cleaved into: GTPase KRas; N-terminally processed] Kras Kras2 Rattus norvegicus (Rat) 189
Q05147 RASK_XENLA GTPase KRas (Ki-Ras) (K-ras) kras Xenopus laevis (African clawed frog) 187
Q07889 SOS1_HUMAN Son of sevenless homolog 1 (SOS-1) SOS1 Homo sapiens (Human) 1333
Q62245 SOS1_MOUSE Son of sevenless homolog 1 (SOS-1) (mSOS-1) Sos1 Mus musculus (Mouse) 1319

Small molecules tested in K-Ras binding assays:

9 datapoints for 8 distinct small molecules


Name comp_4
Affinity Kd (HSQC NMR) 1.3-2 mM
Assay description NMR-spectroscopy-based screen using uniformly 15N-labeled GDP-bound K-Ras
-- Direct single protein target assigned: RASK_HUMAN (Expert curation) --
DOI http://dx.doi.org/10.1002/anie.201201358
Doc title Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation
PDB 4EPV - (0QX)

Name comp_5
Affinity Kd (HSQC NMR) 1.3-2 mM
Assay description NMR-spectroscopy-based screen using uniformly 15N-labeled GDP-bound K-Ras
-- Direct single protein target assigned: RASK_HUMAN (Expert curation) --
DOI http://dx.doi.org/10.1002/anie.201201358
Doc title Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation
PDB 4EPW - (0QV)

Name comp_6
Affinity Kd (HSQC NMR) 1.3-2 mM
Assay description NMR-spectroscopy-based screen using uniformly 15N-labeled GDP-bound K-Ras
-- Direct single protein target assigned: RASK_HUMAN (Expert curation) --
DOI http://dx.doi.org/10.1002/anie.201201358
Doc title Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation
PDB 4EPX - (0QR)

Name comp_13
Affinity Kd (HSQC NMR) 340 uM
Assay description NMR-spectroscopy-based screen using uniformly 15N-labeled GDP-bound K-Ras
-- Direct single protein target assigned: RASK_HUMAN (Expert curation) --
DOI http://dx.doi.org/10.1002/anie.201201358
Doc title Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation
PDB 4EPY - (0QY)

Name comp_2
Affinity Kd (HSQC NMR) 1.3-2 mM
Assay description NMR-spectroscopy-based screen using uniformly 15N-labeled GDP-bound K-Ras
-- Direct single protein target assigned: RASK_HUMAN (Expert curation) --
DOI http://dx.doi.org/10.1002/anie.201201358
Doc title Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation
PDB 4EPT - (0QW)

Name CHEMBL159171
Affinity EC50 = 1065nM
Assay description Inhibition of Ki-Ras
-- Homologous single protein target assigned: RASK_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/21381769
Doc title Macrocycles are great cycles: applications, opportunities, and challenges of synthetic macrocycles in drug discovery.
PDB None

Name CHEMBL2396992
Affinity IC50 = 155uM
Assay description Inhibition of full-length human KRas4B (amino acids 1 to 188)-SOS interaction assessed as inhibition of SOS-mediated nucleotide release activity
-- Direct single protein target assigned: RASK_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23566315
Doc title Targeting mutant KRAS for anticancer therapeutics: a review of novel small molecule modulators.
PDB 4DST - (9LI)

Name CHEMBL2396992
Affinity IC50 = 342uM
Assay description Inhibition of full-length human KRas4B (amino acids 1 to 188)-SOS interaction assessed as inhibition of nucleotide exchange activity
-- Direct single protein target assigned: RASK_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23566315
Doc title Targeting mutant KRAS for anticancer therapeutics: a review of novel small molecule modulators.
PDB 4DST - (9LI)

Name CHEMBL52073
Affinity EC50 > 10uM
Assay description Inhibition of Ki-Ras
-- Homologous single protein target assigned: RASK_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/21381769
Doc title Macrocycles are great cycles: applications, opportunities, and challenges of synthetic macrocycles in drug discovery.
PDB None

31 PDB entries for K-Ras and its protein partners


1AWE
The solution structure of the pleckstrin homology domain of human SOS1. A possible structural role for the sequential association of diffuse B cell lymphoma and pleckstrin homology domains.

Entity type Code Description
polypeptide(L) Q07889 SOS1

1BKD
The structural basis of the activation of Ras by Sos.

Entity type Code Description
polypeptide(L) P01112 H-RAS
polypeptide(L) Q07889 SON OF SEVENLESS-1

1D8D
The basis for K-Ras4B binding specificity to protein farnesyltransferase revealed by 2 A resolution ternary complex structures.

Entity type Code Description
polypeptide(L) Q04631 farnesyltransferase (alpha subunit)
polypeptide(L) Q02293 farnesyltransferase (beta subunit)
polypeptide(L) P01116 K-RAS4B PEPTIDE SUBSTRATE
Ligand FII [(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC ACID

1D8E
The basis for K-Ras4B binding specificity to protein farnesyltransferase revealed by 2 A resolution ternary complex structures.

Entity type Code Description
polypeptide(L) Q04631 FARNESYLTRANSFERASE (ALPHA SUBUNIT)
polypeptide(L) Q02293 FARNESYLTRANSFERASE (BETA SUBUNIT)
polypeptide(L) P01116 K-RAS4B PEPTIDE SUBSTRATE
Ligand FII [(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC ACID

1DBH
Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein.

Entity type Code Description
polypeptide(L) Q07889 PROTEIN (HUMAN SOS 1)

1GBQ
Solution structure of the Grb2 N-terminal SH3 domain complexed with a ten-residue peptide derived from SOS: direct refinement against NOEs, J-couplings and 1H and 13C chemical shifts.

Entity type Code Description
polypeptide(L) Q60631 GRB2
polypeptide(L) Q62245 SOS-1

1NVU
Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS

Entity type Code Description
polypeptide(L) P01112 Transforming protein p21/H-RAS-1
polypeptide(L) Q07889 Son of sevenless protein homolog 1
Ligand GTP GUANOSINE-5'-TRIPHOSPHATE

1NVV
Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS

Entity type Code Description
polypeptide(L) P01112 Transforming protein p21/H-RAS-1
polypeptide(L) P01112 Transforming protein p21/H-RAS-1
polypeptide(L) Q07889 Son of sevenless protein homolog 1
Ligand GNP PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER

1NVW
Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS

Entity type Code Description
polypeptide(L) P01112 Transforming protein p21/H-RAS-1
polypeptide(L) Q07889 Son of sevenless protein homolog 1
Ligand GNP PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER

1NVX
Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS

Entity type Code Description
polypeptide(L) P01112 Transforming protein p21/H-RAS-1
polypeptide(L) Q07889 Son of sevenless protein homolog 1
Ligand GTP GUANOSINE-5'-TRIPHOSPHATE

1PMS
The solution structure of the pleckstrin homology domain of mouse Son-of-sevenless 1 (mSos1).

Entity type Code Description
polypeptide(L) Q62245 SOS 1

1Q9C
Tandem Histone Folds in the Structure of the N-terminal Segment of the Ras Activator Son of Sevenless

Entity type Code Description
polypeptide(L) Q07889 Son of sevenless protein

1XD2
Structural analysis of autoinhibition in the ras activator son of sevenless.

Entity type Code Description
polypeptide(L) P01112 Transforming protein p21/H-Ras-1
polypeptide(L) P01112 Transforming protein p21/H-Ras-1
polypeptide(L) Q07889 Son of sevenless protein homolog 1
Ligand GDP GUANOSINE-5'-DIPHOSPHATE

1XD4
Structural analysis of autoinhibition in the ras activator son of sevenless.

Entity type Code Description
polypeptide(L) Q07889 Son of sevenless protein homolog 1

1XDV
Structural analysis of autoinhibition in the ras activator son of sevenless.

Entity type Code Description
polypeptide(L) Q07889 Son of sevenless protein homolog 1

2GBQ
Solution structure of the Grb2 N-terminal SH3 domain complexed with a ten-residue peptide derived from SOS: direct refinement against NOEs, J-couplings and 1H and 13C chemical shifts.

Entity type Code Description
polypeptide(L) Q60631 GRB2
polypeptide(L) Q62245 SOS-1

2II0
A Ras-induced conformational switch in the Ras activator Son of sevenless.

Entity type Code Description
polypeptide(L) Q07889 Son of sevenless homolog 1

3GBQ
Solution structure of the Grb2 N-terminal SH3 domain complexed with a ten-residue peptide derived from SOS: direct refinement against NOEs, J-couplings and 1H and 13C chemical shifts.

Entity type Code Description
polypeptide(L) Q60631 GRB2
polypeptide(L) Q62245 SOS-1

3GFT
Human K-Ras in complex with a GTP analogue

Entity type Code Description
polypeptide(L) P01116 GTPase KRas
Ligand GNP PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER
Ligand UNX UNKNOWN ATOM OR ION
Ligand CIT CITRIC ACID

3KSY
Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless.

Entity type Code Description
polypeptide(L) Q07889 Son of sevenless homolog 1

4DSN
Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity.

Entity type Code Description
polypeptide(L) P01116 GTPase KRas, isoform 2B
Ligand GCP PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER

4DSO
Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity.

Entity type Code Description
polypeptide(L) P01116 GTPase KRas, isoform 2B
Ligand GSP 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE
Ligand BEN BENZAMIDINE

4DST
Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity.

Entity type Code Description
polypeptide(L) P01116 GTPase KRas, isoform 2B
Ligand 9LI 2-(4,6-DICHLORO-2-METHYL-1H-INDOL-3-YL)ETHANAMINE
Ligand GCP PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER

4DSU
Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity.

Entity type Code Description
polypeptide(L) P01116 GTPase KRas, isoform 2B
Ligand GDP GUANOSINE-5'-DIPHOSPHATE
Ligand BZI BENZIMIDAZOLE

4EPR
Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation.

Entity type Code Description
polypeptide(L) P01116 GTPase KRas
Ligand GDP GUANOSINE-5'-DIPHOSPHATE

4EPT
Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation.

Entity type Code Description
polypeptide(L) P01116 GTPase KRas
Ligand GDP GUANOSINE-5'-DIPHOSPHATE
Ligand 0QW (2-HYDROXYPHENYL)(PYRROLIDIN-1-YL)METHANETHIONE

4EPV
Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation.

Entity type Code Description
polypeptide(L) P01116 GTPase KRas
Ligand GDP GUANOSINE-5'-DIPHOSPHATE
Ligand 0QX 2-(1H-INDOL-3-YLMETHYL)-1H-IMIDAZO[4,5-C]PYRIDINE

4EPW
Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation.

Entity type Code Description
polypeptide(L) P01116 GTPase KRas
Ligand GDP GUANOSINE-5'-DIPHOSPHATE
Ligand 0QV (4-HYDROXYPIPERIDIN-1-YL)(1H-INDOL-3-YL)METHANETHIONE

4EPX
Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation.

Entity type Code Description
polypeptide(L) P01116 GTPase KRas
Ligand GDP GUANOSINE-5'-DIPHOSPHATE
Ligand 0QR N-(6-AMINOPYRIDIN-2-YL)-4-FLUOROBENZENESULFONAMIDE

4EPY
Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation.

Entity type Code Description
polypeptide(L) P01116 GTPase KRas
Ligand GDP GUANOSINE-5'-DIPHOSPHATE
Ligand 0QY N-[2-(1H-INDOL-3-YLMETHYL)-1H-BENZIMIDAZOL-5-YL]-L-PROLINAMIDE

4GBQ
Solution structure of the Grb2 N-terminal SH3 domain complexed with a ten-residue peptide derived from SOS: direct refinement against NOEs, J-couplings and 1H and 13C chemical shifts.

Entity type Code Description
polypeptide(L) Q60631 GRB2
polypeptide(L) Q62245 SOS-1