View source for Kelch-like ECH-associated protein 1 (Rattus norvegicus)

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{{#invoke:InfoboxforTarget|run|Keap1, INrf2|[https://www.uniprot.org/uniprot/P57790 P57790]|Rattus norvegicus|Cys151|[http://pfam.xfam.org/family/PF00651 BTB/POZ domain],<br/>[http://pfam.xfam.org/family/PF01344 Kelch motif]|[[:Category:Kelch-like ECH-associated protein 1 (Rattus norvegicus)|Ligand list]]|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)<br/>
Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its tran-scriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome. (From Uniprot)<br/> 

===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).<br/>
[[File:543_545-disulfide.png|center|600px]]
<div align="center">Mechanism of phase 2 response regulation (PMID: 12193649)</div><br/>
[[File:543_545-function.png|center|600px]]
<div align="center">Cysteine residues in Keap1 sequence</div><br/>

* Hydrophobic property:
:[[File:543-hydro.png||600px]]
* SASA：
:Cys151: Unknown

==Protein Sequence==
<font face="Courier">
MQPEPKPSGA PRSSQFLPLW SKCPEGAGDA VMYASTECKA EVTPSQDGNR <br/>
TFSYTLEDHT KQAFGIMNEL RLSQQLCDVT LQVKYEDIPA AQFMAHKVVL <br/>
ASSSPVFKAM FTNGLREQGM EVVSIEGIHP KVMERLIEFA YTASISVGEK <br/>
<span style="background:#ffff00">'''C'''</span>VLHVMNGAV MYQIDSVVRA CSDFLVQQLD PSNAIGIANF AEQIGCTELH <br/>
QRAREYIYMH FGEVAKQEEF FNLSHCQLAT LISRDDLNVR CESEVFHACI <br/>
DWVKYDCPQR RFYVQALLRA VRCHALTPRF LQTQLQKCEI LQADARCKDY <br/>
LVQIFQELTL HKPTQAVPCR APKVGRLIYT AGGYFRQSLS YLEAYNPSNG <br/>
SWLRLADLQV PRSGLAGCVV GGLLYAVGGR NNSPDGNTDS SALDCYNPMT <br/>
NQWSPCASLS VPRNRSGGGV IDGHIYAVGG SHGCIHHSSV ERYEPDRDEW <br/>
HLVAPMLTRR IGVGVAVLNR LLYAVGGFDG TNRLNSAECY YPERNEWRMI <br/>
TPMNTIRSGA GVCVLHSCIY AAGGYDGQDQ LNSVERYDVE TETWTFVASM <br/>
KHRRSALGIA VHQGRIYVLG GYDGHTFLDS VECYDPDTDT WSEVTRLTSG <br/>
RSGVGVAVTM EPCRKQIDQQ NCTC    <br/> 
</font>

==Structural Information==
*Known structures with covalent ligands: <br/>
:Unknown<br/>

*Protein structure:
[[File:545.png|center|800px]]
<div align="center">Homology structure from hKeap1</div><br/>

==Related Pathway==
*[https://www.genome.jp/kegg-bin/show_pathway?ko04120 Ubiquitin mediated proteolysis] <br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05200 Pathways in cancer] <br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05225 Hepatocellular carcinoma] <br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05418 Fluid shear stress and atherosclerosis] <br/>

==Experimental Evidence==
:Isotope Labeling, UV Spectroscopic 

==Reference==
# 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. [https://www.ncbi.nlm.nih.gov/pubmed/?term=12193649 12193649]<br/> 
# 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. [https://www.ncbi.nlm.nih.gov/pubmed/?term=24896564 24896564]<br/>

[[Category:Targets]]
[[Category:Rattus norvegicus]]
[[Category:Redox protein]]
[[Category:Kelch motif]]
[[Category:BTB/POZ domain]]
[[Category:Ubiquitin mediated proteolysis]]
[[Category:Pathways in cancer]]
[[Category:Hepatocellular carcinoma]]
[[Category:Fluid shear stress and atherosclerosis]]