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:

14 datapoints for 11 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

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)