KEAP1 / INRF2 recombinant protein

Recombinant Human KEAP1 / INRF2 Protein

Cat. Num. AAA2545610

• Gene Names: KEAP1; INrf2; KLHL19
• Purity: > 90 % as determined by SDS-PAGE
• Synonyms: KEAP1 / INRF2; Recombinant Human KEAP1 / INRF2 Protein; KEAP1; KEAP1 / INRF2 recombinant protein

• Host: Baculovirus-Insect Cells
• Purity/Purification: > 90 % as determined by SDS-PAGE
• Form/Format: Lyophilized from sterile 20mM Tris, 500mM NaCl, 3mM DTT, 10% glycerol, pH 7.4
• Sequence Length: 624

• Application Notes: The secreted recombinant human KEAP1 consists of 625 amino acids and predicts a molecular mass of 69.7 KDa. The apparent molecular mass of the protein is approximately 64 KDa in SDS-PAGE under reducing conditions due to glycosylation.
• Predicted N Terminal: Gly
• Endotoxin: < 1.0 EU per mug of the protein as determined by the LAL method
• Preparation and Storage: Samples are stable for up to twelve months from date of receipt at -70 degree C

SDS-PAGE

Related Product Information for KEAP1 / INRF2 recombinant protein

Background: Kelch-like ECH-associated protein 1, also known as cytosolic inhibitor of Nrf2, Kelch-like protein 19, KEAP1 and INRF2, is a cytoplasm and nucleus protein which contains one BACK (BTB/Kelch associated) domain, one BTB (POZ) domain and six Kelch repeats. KEAP1 / INRF2 is broadly expressed, with highest levels in skeletal muscle. KEAP1 / INRF2 is a key regulator of the NRF2 transcription factor, which transactivates the antioxidant response element (ARE) and upregulates numerous proteins involved in antioxidant defense. Under basal conditions, KEAP1 / INRF2 targets NRF2 for ubiquitination and proteolytic degradation and as such is responsible for the rapid turnover of NRF2. KEAP1 / INRF2 retains NFE2L2 / NRF2 in the cytosol. KEAP1 / INRF2 functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. It targets NFE2L2 / NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. KEAP1 / INRF2 may also retain BPTF in the cytosol. It targets PGAM5 for ubiquitination and degradation by the proteasome.

Description: A DNA sequence encoding the human KEAP1 (Q14145) (Gln2-Cys624) was expressed and purified with two additional amino acids (Gly & Pro) at the N-terminus.

NCBI and Uniprot Product Information

• NCBI GI #: 22027642
• NCBI GeneID: 9817
• NCBI Accession #: NP_036421.2
• NCBI GenBank Nucleotide #: NM_012289.3
• UniProt Accession #: Q14145; Q6LEP0; Q8WTX1; Q9BPY9; B3KPD5
• Molecular Weight: 69,666 Da
• NCBI Official Full Name: kelch-like ECH-associated protein 1
• NCBI Official Synonym Full Names: kelch like ECH associated protein 1
• NCBI Official Symbol: KEAP1
• NCBI Official Synonym Symbols: INrf2; KLHL19
• NCBI Protein Information: kelch-like ECH-associated protein 1
• UniProt Protein Name: Kelch-like ECH-associated protein 1
• UniProt Gene Name: KEAP1
• UniProt Synonym Gene Names: INRF2; KIAA0132; KLHL19; INrf2

NCBI Description

This gene encodes a protein containing KELCH-1 like domains, as well as a BTB/POZ domain. Kelch-like ECH-associated protein 1 interacts with NF-E2-related factor 2 in a redox-sensitive manner and the dissociation of the proteins in the cytoplasm is followed by transportation of NF-E2-related factor 2 to the nucleus. This interaction results in the expression of the catalytic subunit of gamma-glutamylcysteine synthetase. Two alternatively spliced transcript variants encoding the same isoform have been found for this gene. [provided by RefSeq, Jul 2008]

Uniprot Description

KEAP1: a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. Has tumor suppressor activity. Retains NRF2, BPTF and PGAM5 in the cytosol. Targets NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and of antioxidant response element-mediated detoxifying enzyme gene expression. Somatic mutations of KEAP1 or NRF2 commonly occur in solid cancers, irrespective of histological type, resulting in the constitutive transcription of cytoprotective genes. Genetic disruption of the KEAP1/CUL3 E3 ubiquitin ligase complex leads to the activation of the NF-kappaB pathway in lung cancer. Alternative activation of the cytoprotective NRF2 pathway exist in the absence of mutations in KEAP1 and HRF2: WTX, PALB2, SQSTM1, and DPP3 can competitively bind KEAP1. These proteins and others that bind KEAP1 contain an ¿ETGE¿ amino acid motif, which matches the KEAP1 interaction motif found in NRF2. Binding of these ¿ETGE¿-containing proteins can displace NRF2, freeing it to translocate to the nucleus and implement its cytoprotective transcriptional pathway. The DPP3 gene is frequently overexpressed in squamous cell lung carcinomas with high wt NRF2 activity. Its expression level significantly correlates with the response rate and progression-free survival of platinum-based first-line chemotherapy. May be a useful biomarker for predicting the chemosensitivity of patients with advanced-stage NSCLC. Broadly expressed, with highest levels in skeletal muscle. Ubiquitination and subsequent degradation of PGAM5 is inhibited by oxidative stress and sulforaphane.

Protein type: Endoplasmic reticulum; Motility/polarity/chemotaxis; Transcription regulation; Ubiquitin conjugating system

Chromosomal Location of Human Ortholog: 19p13.2

Cellular Component: cytoplasm; cytosol; microtubule organizing center; midbody; nucleoplasm

Molecular Function: protein binding; transcription factor binding; ubiquitin-protein ligase activity

Biological Process: cytoplasmic sequestering of transcription factor; negative regulation of transcription factor activity; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; proteasomal ubiquitin-independent protein catabolic process; protein ubiquitination; protein ubiquitination during ubiquitin-dependent protein catabolic process