Kelch-like ECH-associated protein 1 (Rattus norvegicus)

Basic Information
Short Name	Keap1, INrf2
UNP ID	P57790
Organism	Rattus norvegicus
Cys Site	Cys151
Family/Domain	BTB/POZ domain, Kelch motif
Known Ligand	Ligand list
Function Type	Redox protein

Summary

Protein Function

Keap1 (Kelch-like ECH-associated protein 1) is a multi-domain protein which plays a key role in the regulation of Nrf2, a transcription factor that mediates the expression of a large array of cytoprotective enzymes in response to electrophilic and oxidative assault. It acts in concert with members of the CRL3 class of Cullin-RING-Ligase E3 ligases to provide substrate-specific recruitment for ubiquitination, and consists of a three domain architecture composed of an N-terminal BTB (Broad complex, Tramtrack, and Bric-a-Brac) domain, an intervening region (IVR) or BACK domain, and a C-terminal Kelch repeat domain. (PMID: 24896564)

Cys Function & Property

There are 25 cystien residues in Keap1, and could form multiple disulfide bonds or free thiol groups under different situations (see below).

Cysteine residues in Keap1 sequence (PMID: 12193649)

Cysteine residues in Keap1 sequence

• Hydrophobic property:

• SASA：

Cys151: Unknown

Protein Sequence

MQPEPKPSGA PRSSQFLPLW SKCPEGAGDA VMYASTECKA EVTPSQDGNR
TFSYTLEDHT KQAFGIMNEL RLSQQLCDVT LQVKYEDIPA AQFMAHKVVL
ASSSPVFKAM FTNGLREQGM EVVSIEGIHP KVMERLIEFA YTASISVGEK
CVLHVMNGAV MYQIDSVVRA CSDFLVQQLD PSNAIGIANF AEQIGCTELH
QRAREYIYMH FGEVAKQEEF FNLSHCQLAT LISRDDLNVR CESEVFHACI
DWVKYDCPQR RFYVQALLRA VRCHALTPRF LQTQLQKCEI LQADARCKDY
LVQIFQELTL HKPTQAVPCR APKVGRLIYT AGGYFRQSLS YLEAYNPSNG
SWLRLADLQV PRSGLAGCVV GGLLYAVGGR NNSPDGNTDS SALDCYNPMT
NQWSPCASLS VPRNRSGGGV IDGHIYAVGG SHGCIHHSSV ERYEPDRDEW
HLVAPMLTRR IGVGVAVLNR LLYAVGGFDG TNRLNSAECY YPERNEWRMI
TPMNTIRSGA GVCVLHSCIY AAGGYDGQDQ LNSVERYDVE TETWTFVASM
KHRRSALGIA VHQGRIYVLG GYDGHTFLDS VECYDPDTDT WSEVTRLTSG
RSGVGVAVTM EPCRKQIDQQ NCTC

Structural Information

• Known structures with covalent ligands:
  

Unknown

• Protein structure:

Homology structure from hKeap1

Related Pathway

• Ubiquitin mediated proteolysis
  
• Pathways in cancer
  
• Hepatocellular carcinoma
  
• Fluid shear stress and atherosclerosis
  

Experimental Evidence

Isotope Labeling, UV Spectroscopic

Reference

1. Dinkova-Kostova A T, Holtzclaw W D, Cole R N, et al. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants[J]. Proceedings of the National Academy of Sciences, 2002, 99(18): 11908-11913. 12193649
   
2. Cleasby A, Yon J, Day P J, et al. Structure of the BTB domain of Keap1 and its interaction with the triterpenoid antagonist CDDO[J]. PloS one, 2014, 9(6): e98896. 24896564