Keap1

Kelch-like ech-associated protein 1 (cytosolic inhibitor of nrf2)

Reviewed UniProt entries for Keap1 and its protein partners


UniProt code UniProt Name Protein Name Gene Name Organism Length
Q9Z2X8 KEAP1_MOUSE Kelch-like ECH-associated protein 1 (Cytosolic inhibitor of Nrf2) (INrf2) Keap1 Inrf2 Kiaa0132 Mus musculus (Mouse) 624
Q684M4 KEAP1_PIG Kelch-like ECH-associated protein 1 (Cytosolic inhibitor of Nrf2) (INrf2) KEAP1 INRF2 Sus scrofa (Pig) 624
Q5R774 KEAP1_PONAB Kelch-like ECH-associated protein 1 (Cytosolic inhibitor of Nrf2) (INrf2) KEAP1 INRF2 Pongo abelii (Sumatran orangutan) 624
P57790 KEAP1_RAT Kelch-like ECH-associated protein 1 (Cytosolic inhibitor of Nrf2) (INrf2) Keap1 Inrf2 Rattus norvegicus (Rat) 624
Q14145 KEAP1_HUMAN Kelch-like ECH-associated protein 1 (Cytosolic inhibitor of Nrf2) (INrf2) (Kelch-like protein 19) KEAP1 INRF2 KIAA0132 KLHL19 Homo sapiens (Human) 624

Small molecules tested in Keap1 binding assays:

29 datapoints for 18 distinct small molecules


Name CHEMBL1460757
Affinity Kd = 1.9uM
Assay description Binding affinity to Keap1 kelch domain (unknown origin) by competitive SPR assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23562243
Doc title Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction.
PDB None

Name CHEMBL2107333
Affinity Active
Assay description Binding affinity to human recombinant Kelch-DC domain of Keap1 (321 to 609) expressed in HEK293T cells assessed as covalent adduct formation with cysteines at 1 mM after 15 hrs by 2D-FIDA assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23647822
Doc title Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.
PDB None

Name CHEMBL2381964
Affinity Not Active
Assay description Binding affinity to Keap1 kelch domain (unknown origin) by competitive SPR assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23562243
Doc title Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction.
PDB None

Name CHEMBL2381965
Affinity Not Active
Assay description Binding affinity to Keap1 kelch domain (unknown origin) by competitive SPR assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23562243
Doc title Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction.
PDB None

Name CHEMBL2381966
Affinity Not Active
Assay description Binding affinity to Keap1 kelch domain (unknown origin) by competitive SPR assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23562243
Doc title Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction.
PDB None

Name CHEMBL2381967
Affinity Not Active
Assay description Binding affinity to Keap1 kelch domain (unknown origin) by competitive SPR assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23562243
Doc title Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction.
PDB None

Name CHEMBL2381968
Affinity Kd = 1uM
Assay description Binding affinity to Keap1 kelch domain (unknown origin) by competitive SPR assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23562243
Doc title Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction.
PDB None

Name CHEMBL2381969
Affinity Kd = 100uM
Assay description Binding affinity to Keap1 kelch domain (unknown origin) by competitive SPR assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23562243
Doc title Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction.
PDB None

Name CHEMBL2381970
Affinity Kd = 700uM
Assay description Binding affinity to Keap1 kelch domain (unknown origin) by competitive SPR assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23562243
Doc title Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction.
PDB None

Name CHEMBL2402206
Affinity Active
Assay description Binding affinity to human recombinant Kelch-DC domain of Keap1 (321 to 609) expressed in HEK293T cells using [2H]dithiothreitol at 1 mM by NMR-HSQC analysis
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23647822
Doc title Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.
PDB None

Name CHEMBL2402206
Affinity IC50 = 118uM
Assay description Displacement of MR121-Nrf2 from human N-terminal His-tagged Kelch-DC domain of Keap1 (321 to 609) expressed in Escherichia coli BL21 (DE3) after 40 mins by 2D-FIDA assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23647822
Doc title Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.
PDB None

Name CHEMBL2402207
Affinity IC50 = 2.7uM
Assay description Displacement of MR121-Nrf2 from human N-terminal His-tagged Kelch-DC domain of Keap1 (321 to 609) expressed in Escherichia coli BL21 (DE3) after 40 mins by 2D-FIDA assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23647822
Doc title Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.
PDB None

Name CHEMBL2402207
Affinity Not Active
Assay description Binding affinity to human recombinant Kelch-DC domain of Keap1 (321 to 609) expressed in HEK293T cells assessed as covalent adduct formation with cysteines at 1 mM after 15 hrs by 2D-FIDA assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23647822
Doc title Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.
PDB None

Name CHEMBL2402207
Affinity Active
Assay description Binding affinity to human recombinant Kelch-DC domain of Keap1 (321 to 609) expressed in HEK293T cells using [2H]dithiothreitol at 1 mM by NMR-HSQC analysis
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/23647822
Doc title Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.
PDB None

Name CHEMBL256097
Affinity deltaTm = 1degrees C
Assay description Binding affinity to kelch domain of Keap1 (unknown origin) assessed as change in melting temperature after 15 mins by differential scanning fluorimetry assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24417449
Doc title
PDB None

Name CHEMBL3235888
Affinity deltaTm = 4degrees C
Assay description Binding affinity to kelch domain of Keap1 (unknown origin) assessed as change in melting temperature after 15 mins by differential scanning fluorimetry assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24417449
Doc title
PDB None

Name CHEMBL3235889
Affinity deltaTm = 1degrees C
Assay description Binding affinity to kelch domain of Keap1 (unknown origin) assessed as change in melting temperature after 15 mins by differential scanning fluorimetry assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24417449
Doc title
PDB None

Name CHEMBL3235897
Affinity deltaTm = 1degrees C
Assay description Binding affinity to kelch domain of Keap1 (unknown origin) assessed as change in melting temperature after 15 mins by differential scanning fluorimetry assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24417449
Doc title
PDB None

Name CHEMBL3235898
Affinity deltaTm = 2degrees C
Assay description Binding affinity to kelch domain of Keap1 (unknown origin) assessed as change in melting temperature after 15 mins by differential scanning fluorimetry assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24417449
Doc title
PDB None

Name CHEMBL3235901
Affinity deltaTm = 5degrees C
Assay description Binding affinity to kelch domain of Keap1 (unknown origin) assessed as change in melting temperature after 15 mins by differential scanning fluorimetry assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24417449
Doc title
PDB None

Name CHEMBL3237245
Affinity EC50 = 28.6nM
Assay description Displacement of FITC-LDEETGEFL-NH2 from Keap1 Kelch domain (unknown origin) after 30 mins by fluorescence polarization assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24512214
Doc title
PDB None

Name CHEMBL3237245
Affinity Dose-dependent effect
Assay description Inhibition of Keap1-Nrf2 interaction in human HepG2-ARE-C8 cells assessed as activation of Nrf2-ARE luciferase activity after 12 hrs
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24512214
Doc title
PDB None

Name CHEMBL3237245
Affinity Kd = 3.59nM
Assay description Binding affinity to biotinylated Keap1 DC domain (unknown origin) by biolayer interferometry assay
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24512214
Doc title
PDB None

Name CHEMBL3237245
Affinity tde
Assay description Inhibition of Keap1-Nrf2 interaction in human HCT116 cells assessed as increase in Nrf2-induced NQO-1 gene expression at 1 uM by quantitative RT-PCR analysis relative to control
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24512214
Doc title
PDB None

Name CHEMBL3237245
Affinity tde
Assay description Inhibition of Keap1-Nrf2 interaction in human HCT116 cells assessed as increase in Nrf2-induced HO-1 gene expression at 1 uM by quantitative RT-PCR analysis
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24512214
Doc title
PDB None

Name CHEMBL3237245
Affinity Dose-dependent effect
Assay description Inhibition of Keap1-Nrf2 interaction in human HCT116 cells assessed as increase in Nrf2-induced NQO-1 gene expression measured at 8 hrs by quantitative RT-PCR analysis
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24512214
Doc title
PDB None

Name CHEMBL3237245
Affinity tde
Assay description Inhibition of Keap1-Nrf2 interaction in human HCT116 cells assessed as increase in Nrf2-induced GCLM gene expression at 1 uM by quantitative RT-PCR analysis relative to control
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24512214
Doc title
PDB None

Name CHEMBL3237245
Affinity Dose-dependent effect
Assay description Inhibition of Keap1-Nrf2 interaction in human HCT116 cells assessed as increase in Nrf2-induced GCLM gene expression measured at 8 hrs by quantitative RT-PCR analysis
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24512214
Doc title
PDB None

Name CHEMBL3237245
Affinity Dose-dependent effect
Assay description Inhibition of Keap1-Nrf2 interaction in human HCT116 cells assessed as increase in Nrf2-induced HO-1 gene expression measured at 8 hrs by quantitative RT-PCR analysis
-- Direct single protein target assigned: KEAP1_HUMAN (Autocuration) --
DOI http://www.ncbi.nlm.nih.gov/pubmed/24512214
Doc title
PDB None

14 PDB entries for Keap1 and its protein partners


1U6D
Crystal structure of the kelch domain of human keap1

Entity type Code Description
polypeptide(L) Q14145 kelch-like ECH-associated protein 1

1X2J
Structural basis for defects of keap1 activity provoked by its point mutations in lung cancer

Entity type Code Description
polypeptide(L) Q9Z2X8 Kelch-like ECH-associated protein 1

1X2R
Structural basis for defects of keap1 activity provoked by its point mutations in lung cancer

Entity type Code Description
polypeptide(L) Q9Z2X8 Kelch-like ECH-associated protein 1
polypeptide(L) Q60795 Nuclear factor erythroid 2 related factor 2

1ZGK
Conserved solvent and side-chain interactions in the 1.35 Angstrom structure of the Kelch domain of Keap1.

Entity type Code Description
polypeptide(L) Q14145 Kelch-like ECH-associated protein 1

2DYH
Different electrostatic potentials define ETGE and DLG motifs as hinge and latch in oxidative stress response

Entity type Code Description
polypeptide(L) Q9Z2X8 Kelch-like ECH-associated protein 1
polypeptide(L) Q60795 Nrf2/Neh2 peptide from Nuclear factor erythroid 2-related factor 2

2Z32
Structural analysis of the complex of Keap1 with a prothymosin alpha peptide

Entity type Code Description
polypeptide(L) Q9Z2X8 Kelch-like ECH-associated protein 1
polypeptide(L) P26350 Prothymosin alpha

3ADE
The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1

Entity type Code Description
polypeptide(L) Q9Z2X8 Kelch-like ECH-associated protein 1
polypeptide(L) Q64337 Sequestosome-1

3VNG
Crystal Structure of Keap1 in Complex with Synthetic Small Molecular based on a co-crystallization

Entity type Code Description
polypeptide(L) Q14145 Kelch-like ECH-associated protein 1
Ligand FUU 2-(3-((3-(5-(FURAN-2-YL)-1,3,4-OXADIAZOL-2-YL)UREIDO)METHYL)PHENOXY)ACETIC ACID

3VNH
Crystal Structure of Keap1 Soaked with Synthetic Small Molecular

Entity type Code Description
polypeptide(L) Q14145 Kelch-like ECH-associated protein 1
Ligand FUU 2-(3-((3-(5-(FURAN-2-YL)-1,3,4-OXADIAZOL-2-YL)UREIDO)METHYL)PHENOXY)ACETIC ACID

3WDZ
Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy

Entity type Code Description
polypeptide(L) Q9Z2X8 Kelch-like ECH-associated protein 1
polypeptide(L) Q64337 Peptide from Sequestosome-1

3ZGC
Crystal-Contact Engineering to Obtain a Crystal Form of the Kelch Domain of Human Keap1 Suitable for Ligand-Soaking Experiments.

Entity type Code Description
polypeptide(L) Q14145 KELCH-LIKE ECH-ASSOCIATED PROTEIN 1
polypeptide(L) Q16236 NUCLEAR FACTOR ERYTHROID 2-RELATED FACTOR 2

3ZGD
Crystal-Contact Engineering to Obtain a Crystal Form of the Kelch Domain of Human Keap1 Suitable for Ligand-Soaking Experiments.

Entity type Code Description
polypeptide(L) Q14145 KELCH-LIKE ECH-ASSOCIATED PROTEIN 1

4IN4
Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.

Entity type Code Description
polypeptide(L) Q14145 Kelch-like ECH-associated protein 1
Ligand 4ID 2-({5-[(2,4-DIMETHYLPHENYL)SULFONYL]-6-OXO-1,6-DIHYDROPYRIMIDIN-2-YL}SULFANYL)-N-[2-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE

4IQK
Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.

Entity type Code Description
polypeptide(L) Q14145 Kelch-like ECH-associated protein 1
Ligand IQK N,N'-NAPHTHALENE-1,4-DIYLBIS(4-METHOXYBENZENESULFONAMIDE)