Phosphatidylcholine transfer protein

Last updated
PCTP
PDB 1ln2 EBI.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PCTP , Pctp, PC-TP, StarD2, phosphatidylcholine transfer protein
External IDs OMIM: 606055 MGI: 107375 HomoloGene: 32054 GeneCards: PCTP
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001102402
NM_021213
NM_001330377
NM_001330378

NM_008796
NM_001316372

RefSeq (protein)

NP_001095872
NP_001317306
NP_001317307
NP_067036

NP_001303301
NP_032822

Location (UCSC) Chr 17: 55.75 – 55.84 Mb Chr 11: 89.87 – 89.89 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Phosphatidylcholine transfer protein (PCTP), also known as StAR-related lipid transfer domain protein 2 (STARD2), is a specific intracellular phospholipid binding protein that can transfer phosphatidylcholine between different membranes in the cytosol. [5] [6]

Contents

In humans, phosphatidylcholine transfer protein is encoded by the PCTP gene. [7] [8]

Function

PCTP transfers phosphatidylcholine molecules between membranes in vitro . [6] Further studies found that sensitivity to phosphatidylcholine levels causes PCTP to interact with select enzymes, promoting their activation. PCTP stimulates the acyl-CoA thioesterase activity of thioesterase superfamily member 2 (Them2)/acyl-CoA thioesterase 13 (ACOT13) and the activity of homeodomain transcription factor paired box gene 3 (PAX3). [9] Protein kinase C phosphorylation promotes localization of PCTP to the mitochondrion where it may activate Them2. [10]

Structure

This soluble protein is 214 amino acids long. It is almost entirely composed of a StAR-related transfer domain (START). X-ray crystallography shows that this domain forms a pocket that can bind a single molecule of phosphatidylcholine. [11]

This protein also founds the StarD2 subfamily of proteins. This subfamily consists of PCTP, StarD7, StarD10 and collagen type IV alpha-3-binding protein or StarD11, all of which bind phosphatidylcholine except for StarD11 which prefers ceramide.

Tissue distribution and pathology

PCTP is produced in all tissues in the body at various levels. The protein is expressed at high levels in tissues engaged in high metabolism, notably including the liver and macrophages. [6] [12]

No human patients with defects in PCTP have been described to date. Mice lacking PCTP exhibit a resistance to atherosclerosis linked to changes in plasma lipid levels and changes in body weight linked to the level of brown fat use of fatty acids and Them2 activity. [13] [14] Loss of PCTP in fasting mice alters the sensitivity of the liver to insulin, reducing glucose and free fatty acid levels. [15]

Related Research Articles

<span class="mw-page-title-main">Phosphatidylcholine</span> Class of phospholipids

Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup. They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soybeans, from which they are mechanically or chemically extracted using hexane. They are also a member of the lecithin group of yellow-brownish fatty substances occurring in animal and plant tissues. Dipalmitoylphosphatidylcholine (lecithin) is a major component of the pulmonary surfactant, and is often used in the lecithin–sphingomyelin ratio to calculate fetal lung maturity. While phosphatidylcholines are found in all plant and animal cells, they are absent in the membranes of most bacteria, including Escherichia coli. Purified phosphatidylcholine is produced commercially.

<span class="mw-page-title-main">Phosphatidylethanolamine</span> Group of chemical compounds

Phosphatidylethanolamine (PE) is a class of phospholipids found in biological membranes. They are synthesized by the addition of cytidine diphosphate-ethanolamine to diglycerides, releasing cytidine monophosphate. S-Adenosyl methionine can subsequently methylate the amine of phosphatidylethanolamines to yield phosphatidylcholines.

<span class="mw-page-title-main">Phosphatidylethanolamine N-methyltransferase</span> Protein-coding gene in the species Homo sapiens

Phosphatidylethanolamine N-methyltransferase is a transferase enzyme which converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) in the liver. In humans it is encoded by the PEMT gene within the Smith–Magenis syndrome region on chromosome 17.

<span class="mw-page-title-main">Stearoyl-CoA 9-desaturase</span> Class of enzymes

Stearoyl-CoA desaturase (Δ-9-desaturase) is an endoplasmic reticulum enzyme that catalyzes the rate-limiting step in the formation of monounsaturated fatty acids (MUFAs), specifically oleate and palmitoleate from stearoyl-CoA and palmitoyl-CoA. Oleate and palmitoleate are major components of membrane phospholipids, cholesterol esters and alkyl-diacylglycerol. In humans, the enzyme is encoded by the SCD gene.

<span class="mw-page-title-main">ACOT8</span> Protein-coding gene in the species Homo sapiens

Acyl-coenzyme A thioesterase 8 is an enzyme that in humans is encoded by the ACOT8 gene.

<span class="mw-page-title-main">ACOT2</span> Protein-coding gene in the species Homo sapiens

Acyl-CoA thioesterase 2, also known as ACOT2, is an enzyme which in humans is encoded by the ACOT2 gene.

<span class="mw-page-title-main">STARD5</span> Protein-coding gene in the species Homo sapiens

StAR-related lipid transfer protein 5 is a protein that in humans is encoded by the STARD5 gene. The protein is a 213 amino acids long, consisting almost entirely of a StAR-related transfer (START) domain. It is also part of the StarD4 subfamily of START domain proteins, sharing 34% sequence identity with STARD4.

<span class="mw-page-title-main">PITPNB</span> Protein-coding gene in the species Homo sapiens

Phosphatidylinositol transfer protein beta isoform is a protein that in humans is encoded by the PITPNB gene.

<span class="mw-page-title-main">SGMS1</span> Protein-coding gene in the species Homo sapiens

Phosphatidylcholine:ceramide cholinephosphotransferase 1 is an enzyme that in humans is encoded by the SGMS1 gene.

<span class="mw-page-title-main">ACOT11</span> Protein-coding gene in the species Homo sapiens

Acyl-coenzyme A thioesterase 11 also known as StAR-related lipid transfer protein 14 (STARD14) is an enzyme that in humans is encoded by the ACOT11 gene. This gene encodes a protein with acyl-CoA thioesterase activity towards medium (C12) and long-chain (C18) fatty acyl-CoA substrates which relies on its StAR-related lipid transfer domain. Expression of a similar murine protein in brown adipose tissue is induced by cold exposure and repressed by warmth. Expression of the mouse protein has been associated with obesity, with higher expression found in obesity-resistant mice compared with obesity-prone mice. Alternative splicing results in two transcript variants encoding different isoforms.

<span class="mw-page-title-main">ACOT12</span> Protein-coding gene in the species Homo sapiens

Acyl-coenzyme A thioesterase 12 or StAR-related lipid transfer protein 15 (STARD15) is an enzyme that in humans is encoded by the ACOT12 gene. The protein contains a StAR-related lipid transfer domain.

Lipid droplets, also referred to as lipid bodies, oil bodies or adiposomes, are lipid-rich cellular organelles that regulate the storage and hydrolysis of neutral lipids and are found largely in the adipose tissue. They also serve as a reservoir for cholesterol and acyl-glycerols for membrane formation and maintenance. Lipid droplets are found in all eukaryotic organisms and store a large portion of lipids in mammalian adipocytes. Initially, these lipid droplets were considered to merely serve as fat depots, but since the discovery in the 1990s of proteins in the lipid droplet coat that regulate lipid droplet dynamics and lipid metabolism, lipid droplets are seen as highly dynamic organelles that play a very important role in the regulation of intracellular lipid storage and lipid metabolism. The role of lipid droplets outside of lipid and cholesterol storage has recently begun to be elucidated and includes a close association to inflammatory responses through the synthesis and metabolism of eicosanoids and to metabolic disorders such as obesity, cancer, and atherosclerosis. In non-adipocytes, lipid droplets are known to play a role in protection from lipotoxicity by storage of fatty acids in the form of neutral triacylglycerol, which consists of three fatty acids bound to glycerol. Alternatively, fatty acids can be converted to lipid intermediates like diacylglycerol (DAG), ceramides and fatty acyl-CoAs. These lipid intermediates can impair insulin signaling, which is referred to as lipid-induced insulin resistance and lipotoxicity. Lipid droplets also serve as platforms for protein binding and degradation. Finally, lipid droplets are known to be exploited by pathogens such as the hepatitis C virus, the dengue virus and Chlamydia trachomatis among others.

<span class="mw-page-title-main">StAR-related transfer domain</span> Lipid-binding protein domain

START is a lipid-binding domain in StAR, HD-ZIP and signalling proteins. The archetypical domain is found in StAR, a mitochondrial protein that is synthesized in steroid-producing cells. StAR initiates steroid production by mediating the delivery of cholesterol to the first enzyme in steroidogenic pathway. The START domain is critical for this activity, perhaps through the binding of cholesterol. Following the discovery of StAR, 15 START-domain-containing proteins were subsequently identified in vertebrates as well as other that are related.

<span class="mw-page-title-main">Neuropathy target esterase</span> Protein-coding gene in the species Homo sapiens

Neuropathy target esterase, also known as patatin-like phospholipase domain-containing protein 6 (PNPLA6), is an esterase enzyme that in humans is encoded by the PNPLA6 gene.

<span class="mw-page-title-main">STARD4</span> Protein-coding gene in the species Homo sapiens

StAR-related lipid transfer protein 4 (STARD4) is a soluble protein involved in cholesterol transport. It can transfer up to 7 sterol molecules per minute between artificial membranes.

<span class="mw-page-title-main">ACOT6</span> Protein-coding gene in the species Homo sapiens

Acyl-CoA thioesterase 6 is a protein that in humans is encoded by the ACOT6 gene. The protein, also known as C14orf42, is an enzyme with thioesterase activity.

<span class="mw-page-title-main">1-Lysophosphatidylcholine</span>

2-acyl-sn-glycero-3-phosphocholines are a class of phospholipids that are intermediates in the metabolism of lipids. Because they result from the hydrolysis of an acyl group from the sn-1 position of phosphatidylcholine, they are also called 1-lysophosphatidylcholine. The synthesis of phosphatidylcholines with specific fatty acids occurs through the synthesis of 1-lysoPC. The formation of various other lipids generates 1-lysoPC as a by-product.

<span class="mw-page-title-main">Acyl-CoA thioesterase 9</span> Protein-coding gene in the species Homo sapiens

Acyl-CoA thioesterase 9 is a protein that is encoded by the human ACOT9 gene. It is a member of the acyl-CoA thioesterase superfamily, which is a group of enzymes that hydrolyze Coenzyme A esters. There is no known function, however it has been shown to act as a long-chain thioesterase at low concentrations, and a short-chain thioesterase at high concentrations.

<span class="mw-page-title-main">ACOT13</span> Protein-coding gene in the species Homo sapiens

Acyl-CoA thioesterase 13 is a protein that in humans is encoded by the ACOT13 gene. This gene encodes a member of the thioesterase superfamily. In humans, the protein co-localizes with microtubules and is essential for sustained cell proliferation.

<span class="mw-page-title-main">ACOT1</span> Protein-coding gene in the species Homo sapiens

Acyl-CoA thioesterase 1 is a protein that in humans is encoded by the ACOT1 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000141179 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020553 - Ensembl, May 2017
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  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  6. 1 2 3 Wirtz KW (July 1991). "Phospholipid transfer proteins". Annu. Rev. Biochem. 60 (13): 73–99. doi:10.1146/annurev.bi.60.070191.000445. PMID   1883207.
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  10. de Brouwer AP, Westerman J, Kleinnijenhuis A, Bevers LE, Roelofsen B, Wirtz KW (March 2002). "Clofibrate-induced relocation of phosphatidylcholine transfer protein to mitochondria in endothelial cells". Exp. Cell Res. 274 (1): 100–11. doi:10.1006/excr.2001.5460. hdl: 1874/14384 . PMID   11855861. S2CID   21938117.
  11. Roderick SL, Chan WW, Agate DS, Olsen LR, Vetting MW, Rajashankar KR, Cohen DE (July 2002). "Structure of human phosphatidylcholine transfer protein in complex with its ligand". Nature Structural & Molecular Biology. 9 (7): 507–11. doi:10.1038/nsb812. PMID   12055623. S2CID   8208598.
  12. Baez JM, Tabas I, Cohen DE (May 2005). "Decreased lipid efflux and increased susceptibility to cholesterol-induced apoptosis in macrophages lacking phosphatidylcholine transfer protein". Biochem. J. 388 (Pt 1): 57–63. doi:10.1042/BJ20041899. PMC   1186693 . PMID   15628972.
  13. Wang WJ, Baez JM, Maurer R, Dansky HM, Cohen DE (2006). "Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E deficient mice". J. Lipid Res. 47 (11): 2400–7. doi: 10.1194/jlr.M600277-JLR200 . PMID   16940277.
  14. Kang HW, Ribich S, Kim BW, Hagen SJ, Bianco AC, Cohen DE (November 2009). "Mice lacking Pctp /StarD2 exhibit increased adaptive thermogenesis and enlarged mitochondria in brown adipose tissue". J. Lipid Res. 50 (11): 2212–21. doi:10.1194/jlr.M900013-JLR200. PMC   2759827 . PMID   19502644.
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