Cholesteryl ester transfer protein (CETP)
The protein contains 493 amino acids for an estimated molecular weight of 54756 Da.
Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles. Allows the net movement of cholesteryl ester from high density lipoproteins/HDL to triglyceride-rich very low density lipoproteins/VLDL, and the equimolar transport of triglyceride from VLDL to HDL (PubMed:3600759, PubMed:24293641, PubMed:3281933). Regulates the reverse cholesterol transport, by which excess cholesterol is removed from peripheral tissues and returned to the liver for elimination (PubMed:17237796). (updated: June 17, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
Biological Process
Cholesterol homeostasis
Cholesterol metabolic process
Cholesterol transport
High-density lipoprotein particle remodeling
Intracellular receptor signaling pathway
Lipid homeostasis
Lipid transport
Lipoprotein metabolic process
Low-density lipoprotein particle remodeling
Negative regulation of macrophage derived foam cell differentiation
Phosphatidylcholine metabolic process
Phospholipid homeostasis
Phospholipid transport
Positive regulation of cholesterol transport
Positive regulation of phospholipid transport
Receptor-mediated endocytosis
Regulation of cholesterol efflux
Reverse cholesterol transport
Small molecule metabolic process
Transmembrane transport
Triglyceride homeostasis
Triglyceride metabolic process
Triglyceride transport
Very-low-density lipoprotein particle remodeling
The reference OMIM entry for this protein is 118470
Cholesteryl ester transfer protein, plasma; cetp
Lipid transfer protein i
DESCRIPTION
The cholesteryl ester transfer protein (CETP) mediates the exchange of lipids between lipoproteins, resulting in the net transfer of cholesteryl ester from high density lipoprotein (HDL) to other lipoproteins and in the subsequent uptake of cholesterol by hepatocytes (summary by Kuivenhoven et al., 1998).CLONING
Using a partial amino acid sequence from purified CETP, Drayna et al. (1987) cloned and sequenced cDNA encoding CETP from a human liver library. They used the sequenced cDNA to detect CETP mRNA in a number of human tissues. CETP is also known as lipid transfer protein I (Day et al., 1994).GENE FUNCTION
Because the role of CETP in atherosclerosis remained unclear, Okamoto et al. (2000) attempted to develop a potent, specific CETP inhibitor. One inhibitor, JTT-705, forms a disulfide bond with CETP and increases high density lipoprotein (HDL) cholesterol, decreases non-HDL cholesterol, and inhibits the progression of atherosclerosis in rabbits. These observations suggested that CETP may be atherogenic in vivo and that JTT-705 may be a potential antiatherogenic drug.GENE STRUCTURE
Oliveira et al. (1996) used transgenic mice to map the cis-acting sequences of the CETP gene. They localized a dietary cholesterol positive response element to the interval between -370 bp and -138 bp in the 5-prime proximal promoter region. Oliveira et al. (1996) found that more distal 5-prime promoter regions are required for tissue-specific expression in the liver, spleen, small intestine, adrenal gland, and other tissues.MAPPING
Sparkes et al. (1987) used a CETP probe against DNA from a human/mouse somatic cell hybrid panel to assign the CETP gene to chromosome 16. In situ hybridization of the same probe to metaphase chromosomes regionalized the gene to 16q21. See also Lusis et al. (1987). This contributes a new marker for chromosome 16 inasmuch as RFLPs of this gene have been reported (Drayna and Lawn, 1987).MOLECULAR GENETICS
For a discussion of the relationship between variation in the CETP gene and HDL cholesterol levels, see 143470.ANIMAL MODEL
The acceleration of atherosclerosis by polygenic (essential) hypertension is well recognized in humans; however, the lack of an animal model that simulates the human disease hinders elucidation of pathogenic mechanisms. Herrera et al. (1999) reported a transgenic atherosclerosis-polygenic hypertension model in Dahl salt-sensitive hypertensive rats that overexpress the human cholesteryl ester transfer protein. Male transgenic rats fed regular rat chow showed age-dependent severe combined hyperlipidemia, atherosclerotic lesions, myocardial infarctions, and decreased survival. These findings differed from various mouse atherosclerosis models, demonstrating the necessity of complex disease modeling in different species. The data demonstrated that CETP can be proatherogenic. To determine the relationship between apolipoprotein C-I (APOC1; 107710) and CETP, Gautier et al. (2002) crossed transgenic mice expressing human CETP with Apoc1 null mice. The HDLs of these crosses contained 50% less cholesteryl esters and showed a decreased cholesteryl ester-to-triglyceride ratio. The mean apparent diameter of LDLs from these mice was also significantly reduced. In vitro, purified Apoc1 inhibited cholesteryl ester exchange when added to either total plasma or to reconstituted HDL-free mixtures. Gautier et al. (2002) concluded tha ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for CETP
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 118470 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed