Cholesteryl ester transfer protein, plasma |
PDB rendering based on 2obd. |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
2OBD, 4EWS, 4F2A
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Identifiers |
Symbols |
CETP; BPIFF; HDLCQ10 |
External IDs |
OMIM: 118470 HomoloGene: 47904 ChEMBL: 3572 GeneCards: CETP Gene |
Gene Ontology |
Molecular function |
• lipid transporter activity
• phospholipid transporter activity
• lipid binding
• cholesterol binding
• cholesterol transporter activity
• triglyceride binding
• phosphatidylcholine binding
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Cellular component |
• extracellular region
• extracellular space
• vesicle
• high-density lipoprotein particle
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Biological process |
• lipid metabolic process
• triglyceride metabolic process
• lipid transport
• receptor-mediated endocytosis
• cholesterol metabolic process
• negative regulation of macrophage derived foam cell differentiation
• regulation of cholesterol efflux
• phospholipid transport
• cholesterol transport
• very-low-density lipoprotein particle remodeling
• low-density lipoprotein particle remodeling
• high-density lipoprotein particle remodeling
• lipoprotein metabolic process
• cholesterol homeostasis
• reverse cholesterol transport
• small molecule metabolic process
• phosphatidylcholine metabolic process
• lipid homeostasis
• phospholipid homeostasis
• triglyceride homeostasis
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Sources: Amigo / QuickGO |
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RNA expression pattern |
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More reference expression data |
Orthologs |
Species |
Human |
Mouse |
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Entrez |
1071 |
n/a |
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Ensembl |
ENSG00000087237 |
n/a |
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UniProt |
P11597 |
n/a |
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RefSeq (mRNA) |
NM_000078 |
n/a |
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RefSeq (protein) |
NP_000069 |
n/a |
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Location (UCSC) |
Chr 16:
57 – 57.02 Mb |
n/a |
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PubMed search |
[1] |
n/a |
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Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. It collects triglycerides from very-low-density (VLDL) or low-density lipoproteins (LDL) and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), and vice versa. Most of the time, however, CETP does a homoexchange, trading a triglyceride for a cholesteryl ester or a cholesteryl ester for a triglyceride.
Contents
- 1 Genetics
- 2 Role in disease
- 3 Pharmacology
- 4 Interactive pathway map
- 5 References
- 6 Further reading
- 7 External links
Genetics[edit]
The CETP gene is located on the sixteenth chromosome (16q21).
Role in disease[edit]
Rare mutations leading to increased function of CETP have been linked to accelerated atherosclerosis.[1] In contrast, a polymorphism (I405V) of the CETP gene leading to lower serum levels has also been linked to exceptional longevity [2] and to metabolic response to nutritional intervention.[3] However, this mutation also increases the prevalence of coronary heart disease in patients with hypertriglyceridemia.[4] The D442G mutation, which lowers CETP levels and increases HDL levels also increases coronary heart disease.[1]
Elaidic acid, a major component of trans fat, increases CETP activity.[5]
Pharmacology[edit]
See also: CETP inhibitor
As HDL can alleviate atherosclerosis and other cardiovascular diseases, and certain disease states such as the metabolic syndrome feature low HDL, pharmacological inhibition of CETP is being studied as a method of improving HDL levels.[6] To be specific, in a 2004 study, the small molecular agent torcetrapib was shown to increase HDL levels, alone and with a statin, and lower LDL when co-administered with a statin.[7] Studies into cardiovascular endpoints, however, were largely disappointing. While they confirmed the change in lipid levels, most reported an increase in blood pressure, no change in atherosclerosis,[8][9] and, in a trial of a combination of torcetrapib and atorvastatin, an increase in cardiovascular events and mortality.[10]
A compound related to torcetrapib, Dalcetrapib (investigative name JTT-705/R1658), was also being studied, but trials have since been ceased.[11] It increases HDL levels by 30%, as compared to 60% by torcetrapib.[12] Another CETP inhibitor under development is Merck's MK-0859 anacetrapib, which in initial studies is not shown to increase blood pressure.[13]
Interactive pathway map[edit]
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".
References[edit]
- ^ a b Zhong S, Sharp DS, Grove JS, Bruce C, Yano K, Curb JD, Tall AR (June 1996). "Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels". J Clin Invest 97 (12): 2917–23. doi:10.1172/JCI118751. ISSN 0021-9738. PMC 507389. PMID 8675707.
- ^ Barzilai N, Atzmon G, Schechter C, Schaefer EJ, Cupples AL, Lipton R, Cheng S, Shuldiner AR (October 2003). "Unique lipoprotein phenotype and genotype associated with exceptional longevity". JAMA 290 (15): 2030–40. doi:10.1001/jama.290.15.2030. ISSN 0098-7484. PMID 14559957.
- ^ Darabi M, Abolfathi AA, Noori M, Kazemi A, Ostadrahimi A, Rahimipour A et al. (2009). "Cholesteryl ester transfer protein I405V polymorphism influences apolipoprotein A-I response to a change in dietary fatty acid composition". Horm Metab Res 41 (7): 554–8. doi:10.1055/s-0029-1192034. PMID 19242900.
- ^ Bruce C, Sharp DS, Tall AR (1 May 1998). "Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia". J Lipid Res 39 (5): 1071–8. ISSN 0022-2275. PMID 9610775.
- ^ Abbey M, Nestel PJ (March 1994). "Plasma cholesteryl ester transfer protein activity is increased when trans-elaidic acid is substituted for cis-oleic acid in the diet". Atherosclerosis 106 (1): 99–107. doi:10.1016/0021-9150(94)90086-8. ISSN 0021-9150. PMID 8018112.
- ^ Barter PJ, Brewer HB Jr, Chapman MJ, Hennekens CH, Rader DJ, Tall AR (February 2003). "Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis". Arterioscler Thromb Vasc Biol 23 (2): 160–7. doi:10.1161/01.ATV.0000054658.91146.64. ISSN 1079-5642. PMID 12588754.
- ^ Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, Mancuso JP, Rader DJ (April 2004). "Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol". N Engl J Med 350 (15): 1505–15. doi:10.1056/NEJMoa031766. ISSN 0028-4793. PMID 15071125.
- ^ Steven E. Nissen, M.D.; Jean-Claude Tardif, M.D.; Stephen J. Nicholls, M.B., B.S., Ph.D.; James H. Revkin, M.D.; Charles L. Shear, Dr.P.H.; William T. Duggan, Ph.D.; Witold Ruzyllo, M.D.; William B. Bachinsky, M.D.; Gabriel P. Lasala, M.D.; E. Murat Tuzcu, M.D. for the ILLUSTRATE Investigators (March 2007). "Effect of torcetrapib on the progression of coronary atherosclerosis". N Engl J Med 356 (13): 1304–16. doi:10.1056/NEJMoa070635. ISSN 0028-4793. PMID 17387129. Retrieved 24 January 2014.
- ^ Kastelein JJ, van Leuven SI; Van Leuven, Michiel L.; Burgess, Leslie; Evans, Greg W.; Kuivenhoven, Jan A.; Barter, Philip J.; Revkin, James H.; Grobbee, Diederick E.; Riley, Ward A.; Shear, Charles L.; Duggan; Bots, Michiel L.; Radiance 1, Investigators (April 2007). "Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia" (abstract). N Engl J Med 356 (16): 1620–30. doi:10.1056/NEJMoa071359. ISSN 0028-4793. PMID 17387131.
- ^ "Pfizer Stops All Torcetrapib Clinical Trials in Interest of Patient Safety" (Press release). U.S. Food and Drug Administration. 2006-12-03.
- ^ El Harchaoui K, van der Steeg WA, Stroes ES, Kastelein JJ (August 2007). "The role of CETP inhibition in dyslipidemia". Curr Atheroscler Rep 9 (2): 125–33. doi:10.1007/s11883-007-0008-5. ISSN 1523-3804. PMID 17877921.
- ^ de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, de Graaf J, Zwinderman AH, Posma JL, van Tol A, Kastelein JJ (May 2002). "Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study". Circulation 105 (18): 2159–65. doi:10.1161/01.CIR.0000015857.31889.7B. ISSN 0009-7322. PMID 11994249.
- ^ Reuters (2007-10-04). "Merck announces its investigational CETP-Inhibitor, MK-0859, produced positive effects on lipids with no observed blood pressure changes". Reuters, Inc. Retrieved 26 November 2013.
Further reading[edit]
- Okajima F (March 2002). "[Distribution of sphingosine 1-phosphate in plasma lipoproteins and its role in the regulation of the vascular cell functions]". Tanpakushitsu Kakusan Koso 47 (4 Suppl): 480–7. ISSN 0039-9450. PMID 11915346.
- Barter PJ, Brewer HB, Chapman MJ et al. (February 2003). "Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis" (Free full text). Arterioscler. Thromb. Vasc. Biol. 23 (2): 160–7. doi:10.1161/01.ATV.0000054658.91146.64. ISSN 1079-5642. PMID 12588754.
- Dallinga-Thie GM, Dullaart RP, van Tol A (June 2007). "Concerted actions of cholesteryl ester transfer protein and phospholipid transfer protein in type 2 diabetes: effects of apolipoproteins". Curr. Opin. Lipidol. 18 (3): 251–7. doi:10.1097/MOL.0b013e3280e12685. ISSN 0957-9672. PMID 17495597.
PDB gallery
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2obd: Crystal Structure of Cholesteryl Ester Transfer Protein
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External links[edit]
- Cholesterol ester transfer proteins at the US National Library of Medicine Medical Subject Headings (MeSH)
Protein, glycoconjugate: glycoproteins and glycopeptides
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Mucoproteins |
Mucin
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- CD43
- CD164
- MUC1
- MUC2
- MUC3A
- MUC3B
- MUC4
- MUC5AC
- MUC5B
- MUC6
- MUC7
- MUC8
- MUC12
- MUC13
- MUC15
- MUC16
- MUC17
- MUC19
- MUC20
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Other
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- Haptoglobin
- Intrinsic factor
- Orosomucoid
- Peptidoglycan
- Phytohaemagglutinin
- Ovomucin
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Proteoglycans |
CS/DS
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- Decorin
- Biglycan
- Versican
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HS/CS
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CS
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- Chondroitin sulfate proteoglycans: Aggrecan
- Neurocan
- Brevican
- CD44
- CSPG4
- CSPG5
- Platelet factor 4
- Structural maintenance of chromosomes 3
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KS
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- Fibromodulin
- Lumican
- Keratocan
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HS
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Other |
- Activin and inhibin
- ADAM
- Alpha 1-antichymotrypsin
- Apolipoprotein H
- CD70
- Asialoglycoprotein
- Avidin
- B-cell activating factor
- 4-1BB ligand
- Cholesterylester transfer protein
- Clusterin
- Colony-stimulating factor
- Hemopexin
- Lactoferrin
- Membrane glycoproteins
- Myelin protein zero
- Osteonectin
- Protein C
- Protein S
- Serum amyloid P component
- Sialoglycoprotein
- CD43
- Glycophorin
- Glycophorin C
- Thrombopoietin
- Thyroglobulin
- Thyroxine-binding proteins
- Transcortin
- Tumor necrosis factor alpha
- Uteroglobin
- Vitronectin
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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- Biochemical families: carbohydrates
- alcohols
- glycoproteins
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- eicosanoids
- fatty acids / intermediates
- phospholipids
- sphingolipids
- steroids
- nucleic acids
- constituents / intermediates
- proteins
- Amino acids / intermediates
- tetrapyrroles / intermediates
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Proteins: carrier proteins
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Fatty acid |
- FABP1
- FABP2
- FABP3
- FABP4
- FABP5
- FABP6
- FABP7
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Hormone |
- peptide hormone: Follistatin
- Growth hormone binding protein
- Insulin-like growth factor binding protein
- IGFBP1
- IGFBP2
- IGFBP3
- IGFBP4
- IGFBP5
- IGFBP6
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- Neurophysins
- steroid hormone: Sex hormone binding globulin/Androgen binding protein
- Transcortin
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- Transthyretin
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Metal/element |
- calcium
- Calcium-binding protein
- Calmodulin-binding proteins
- copper
- iron
- Iron-binding proteins
- Transferrin receptor
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Vitamin |
- Retinol binding protein
- Transcobalamin
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Other |
- Acyl carrier protein
- Adaptor protein
- Cholesterylester transfer protein
- F-box protein
- GTP-binding protein
- Latent TGF-beta binding protein
- Light-harvesting complex
- Major urinary proteins
- Membrane transport protein
- Odorant binding protein
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B proteins: BY STRUCTURE: membrane, globular (en, ca, an), fibrous
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Lipids: lipoprotein particle metabolism
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Lipoprotein particle classes and subclasses |
- delivery of TGs: Chylomicron
- VLDL
- delivery of C and CE: IDL
- LDL
- lb LDL
- sd LDL
- Lp(a)
- HDL
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Apolipoproteins |
- APOA
- APOB
- APOC
- APOD
- APOE
- APOH
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Extracellular enzymes |
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Lipid transfer proteins |
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Cell surface receptors |
- IDL: LRP
- LRP1
- LRP1B
- LRP2
- LRP3
- LRP4
- LRP5
- LRP5L
- LRP6
- LRP8
- LRP10
- LRP11
- LRP12
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ATP-binding cassette transporter |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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