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Gene Symbol |
KEAP1 |
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Aliases |
INrf2, KLHL19 |
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Entrez Gene ID |
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Gene Name |
Kelch like ECH associated protein 1 |
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Chromosomal Location |
19p13.2 |
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HGNC ID |
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Summary |
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]
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e!Ensembl
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Gene Ontology (GO)
| GO ID |
Ontology |
Function |
Evidence |
Reference |
| GO:0010499 |
Biological process |
Proteasomal ubiquitin-independent protein catabolic process |
IDA |
15983046 |
| GO:0016567 |
Biological process |
Protein ubiquitination |
IDA |
15983046 |
| GO:0032436 |
Biological process |
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process |
TAS |
17015834 |
| GO:0042994 |
Biological process |
Cytoplasmic sequestering of transcription factor |
IBA |
21873635 |
| GO:0043433 |
Biological process |
Negative regulation of DNA-binding transcription factor activity |
TAS |
17015834 |
| GO:0005737 |
Cellular component |
Cytoplasm |
IDA |
19424503 |
| GO:0005829 |
Cellular component |
Cytosol |
TAS |
17015834 |
| GO:0030496 |
Cellular component |
Midbody |
IDA |
15166316 |
| GO:0031463 |
Cellular component |
Cul3-RING ubiquitin ligase complex |
IDA |
15983046 |
| GO:0005515 |
Molecular function |
Protein binding |
IPI |
16189514, 16888629, 17015834, 17510365, 18757741, 19424503, 19615732, 19706542, 20173742, 20452972, 20562859, 20600852, 21044950, 21516116, 21903422, 21988832, 23274085, 24089205, 25416956, 25910212, 26517842, 26649820 |
| GO:0008134 |
Molecular function |
Transcription factor binding |
IBA |
21873635 |
| GO:0008134 |
Molecular function |
Transcription factor binding |
IPI |
17015834 |
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| Protein Information |
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Protein Name |
Kelch-like ECH-associated protein 1, KEAP1 delta C, cytosolic inhibitor of Nrf2, kelch-like family member 19, kelch-like protein 19 |
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Function |
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Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination (PubMed:14585973, PubMed:15379550, PubMed:15572695, PubMed:15983046, PubMed:15601839). KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (PubMed:19489739, PubMed:16006525, PubMed:17127771, PubMed:18251510, PubMed:29590092). In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2 (PubMed:20452972). The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation (PubMed:28380357). The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome (PubMed:15379550, PubMed:17046835). |
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UniProt |
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PDB |
5NLB, 1U6D, 1ZGK, 2FLU, 3VNG, 3VNH, 3ZGC, 3ZGD, 4CXI, 4CXJ, 4CXT, 4IFJ, 4IFL, 4IFN, 4IN4, 4IQK, 4L7B, 4L7C, 4L7D, 4N1B, 4XMB, 5DAD, 5DAF, 5F72, 5GIT, 5WFL, 5WFV, 5WG1, 5WHL, 5WHO, 5WIY, 5X54, 6FFM, 6FMP, 6FMQ |
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Interactions |
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| STRING |
MINT |
IntAct |
| ENSP00000266718 |
P51884 |
P51884 |
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View interactions
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Associated Diseases
| Disease group | Disease Name | References |
| Digestive System Diseases |
| Cholangitis |
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| Gastrointestinal Diseases |
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| Hepatitis |
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| Colitis |
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| Crohn Disease |
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| Cholera Infantum |
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| Endocrine System Diseases |
| PCOS |
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| Musculoskeletal Diseases |
| Spondylitis |
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| Neoplasms |
| Renal Cancer |
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| Gall Bladder Cancer |
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| Lung Cancer |
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| Prostate cancer |
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| Skin and Connective Tissue Diseases |
| Keratosis |
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| Psoriasis |
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References |
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| Lu Jiayin, Wang Zixu, Cao Jing, Chen Yaoxing, Dong Yulan |
| Laboratory of Neurobiology, College of Animal Medicine, China Agricultural University, Haidian, Beijing, 100193, People's Republic of China.| Laboratory of Neurobiology, College of Animal Medicine, China Agricultural University, Haidian, Beijing, 100193, People's Republic of China.| Laboratory of Neurobiology, College of Animal Medicine, China Agricultural University, Haidian, Beijing, 100193, People's Republic of China.| Laboratory of Neurobiology, College of Animal Medicine, China Agricultural University, Haidian, Beijing, 100193, People's Republic of China. yxchen@cau.edu.cn.| Laboratory of Neurobiology, College of Animal Medicine, China Agricultural University, Haidian, Beijing, 100193, People's Republic of China. ylbcdong@cau.edu.cn. |
| Reprod Biol Endocrinol. 2018 Aug 20;16(1):80. doi: 10.1186/s12958-018-0391-5. |
Abstract
In recent years, the study of oxidative stress (OS) has become increasingly popular. In particular, the role of OS on female fertility is very important and has been focused on closely. The occurrence of OS is due to the excessive production of reactive oxygen species (ROS). ROS are a double-edged sword; they not only play an important role as secondary messengers in many intracellular signaling cascades, but they also exert indispensable effects on pathological processes involving the female genital tract. ROS and antioxidants join in the regulation of reproductive processes in both animals and humans. Imbalances between pro-oxidants and antioxidants could lead to a number of female reproductive diseases. This review focuses on the mechanism of OS and a series of female reproductive processes, explaining the role of OS in female reproduction and female reproductive diseases caused by OS, including polycystic ovary syndrome (PCOS), endometriosis, preeclampsia and so on. Many signaling pathways involved in female reproduction, including the Keap1-Nrf2, NF-kappaB, FOXO and MAPK pathways, which are affected by OS, are described, providing new ideas for the mechanism of reproductive diseases. |
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| © 2019, Biomedical Informatics Centre, NIRRH |
National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai-400 012
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