Phospholipid transfer protein (PLTP)
The protein contains 493 amino acids for an estimated molecular weight of 54739 Da.
Mediates the transfer of phospholipids and free cholesterol from triglyceride-rich lipoproteins (low density lipoproteins or LDL and very low density lipoproteins or VLDL) into high-density lipoproteins (HDL) as well as the exchange of phospholipids between triglyceride-rich lipoproteins themselves (PubMed:7654777, PubMed:9132017, PubMed:11013307, PubMed:19321130, PubMed:21515415, PubMed:29883800). Facilitates the transfer of a spectrum of different lipid molecules, including diacylglycerol, phosphatidic acid, sphingomyelin, phosphatidylcholine, phosphatidylinositol, phosphatidylglycerol, cerebroside and phosphatidyl ethanolamine (PubMed:9132017). Plays an important role in HDL remodeling which involves modulating the size and composition of HDL (PubMed:29883800). Also plays a key role in the uptake of cholesterol from peripheral cells and tissues that is subsequently transported to the liver for degradation and excretion (PubMed:21736953). Two distinct forms of PLTP exist in plasma: an active form that can transfer phosphatidylcholine from phospholipid vesicles to HDL, and an inactive form that lacks this capability (PubMed:11013307). (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.
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Biological Process
Ceramide transport
Flagellated sperm motility
Glycolipid transport
High-density lipoprotein particle remodeling
Intracellular receptor signaling pathway
Lipid metabolic process
Lipid transport
Phospholipid transport
Positive regulation of cholesterol efflux
Vitamin E biosynthetic process
Cellular Component
Extracellular region
Extracellular space
High-density lipoprotein particle
Nucleus
Molecular Function
Ceramide binding
Ceramide transfer activity
Ceramide transporter activity
Cerebroside transfer activity
Cholesterol transfer activity
Diacylglyceride transfer activity
Diacylglycerol binding
High-density lipoprotein particle binding
Lipid binding
Lipid transporter activity
Low-density lipoprotein particle binding
Phosphatidic acid binding
Phosphatidic acid transfer activity
Phosphatidylcholine binding
Phosphatidylcholine transfer activity
Phosphatidylcholine transporter activity
Phosphatidylethanolamine binding
Phosphatidylethanolamine transfer activity
Phosphatidylglycerol binding
Phosphatidylglycerol transfer activity
Phosphatidylinositol transfer activity
Phospholipid transfer activity
Phospholipid transporter activity
Sphingomyelin transfer activity
Very-low-density lipoprotein particle binding
The reference OMIM entry for this protein is 172425
Phospholipid transfer protein; pltp
Lipid transfer protein ii high density lipoprotein cholesterol level quantitative trait locus 9, included; hdlcq9, included
CLONING
Human plasma contains at least 2 different lipid transfer proteins: cholesteryl ester transfer protein (118470), also referred to as lipid transfer protein I, and phospholipid transfer protein (PLTP), also referred to as lipid transfer protein II. Day et al. (1994) purified phospholipid transfer protein with an apparent molecular mass of 81 kD from human plasma. From the NH2-terminal amino acid sequence, they designed primers for polymerase chain reaction and isolated a full-length cDNA from a human endothelial cDNA library. The cDNA was 1,750 bp long and contained an open reading frame of 1,518 nucleotides encoding a leader of 17 amino acids and a mature protein of 476 residues.GENE FUNCTION
Tu et al. (1995) identified the functional promoter of the PLTP gene. The promoter consists of a TATA box, a high-GC content region, and several consensus sequences for the potential binding of transcription factors. A minimal promoter of 159 bp between -230 and -72 relative to the first transcriptional initiation site was responsible for the full activity. Two transcription factor-binding motifs, SP1 and AP-2, are located within this area. It appeared that the PLTP promoter activity relies primarily on the putative cis-elements in the functional region.MAPPING
Using a human/rodent somatic cell hybrid mapping panel, Day et al. (1994) mapped the PLTP gene to chromosome 20. Whitmore et al. (1995) narrowed the assignment to 20q12-q13.1 by fluorescence in situ hybridization. LeBoeuf et al. (1996) demonstrated that the Pltp gene maps to the distal portion of mouse chromosome 2.MOLECULAR GENETICS
In an evaluation of the hypothesis that multiple high density lipoprotein cholesterol (HDL-C) levels reflect the cumulative contributions of multiple common DNA sequence variants, each of which has a small effect, Spirin et al. (2007) identified a single-nucleotide polymorphism (SNP) of the PLTP gene (172425.0001) that acts in concert with other SNPs in the CETP (118470.0005) and LPL (118470.0042) genes to affect plasma levels of high density lipoprotein cholesterol. In a metaanalysis of plasma lipid concentrations in greater than 100,000 individuals of European descent, Teslovich et al. (2010) identified dbSNP rs6065906 near the PLTP gene as having an effect on HDL cholesterol concentrations as well as triglyceride with an effect size of -0.93 mg per deciliter and a P value of 2 x 10(-22).ANIMAL MODEL
Using homologous recombination in embryonic stem cells, Jiang et al. (1999) produced mice with no PLTP gene expression. Reduced plasma PLTP activity caused markedly decreased high density lipoprotein (HDL) lipid and apoprotein, demonstrating the importance of transfer surface components of triglyceride-rich lipoproteins in the maintenance of HDL levels. Vesicular lipoproteins accumulating in PLTP -/- mice on a high-fat diet could influence the development of atherosclerosis. ... 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
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for PLTP
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 172425 was added.