Phosphatidylcholine transfer protein

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]

PCTP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1LN1, 1LN2, 1LN3
Identifiers
Aliases	PCTP, Pctp, PC-TP, StarD2, phosphatidylcholine transfer protein
External IDs	OMIM: 606055 MGI: 107375 HomoloGene: 32054 GeneCards: PCTP
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q22 Start 55,751,051 bp[1] End 55,842,830 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 C|11 54.7 cM Start 89,982,665 bp[2] End 90,002,894 bp[2]
Gene ontology Molecular function • GO:0001948 protein binding • phosphatidylcholine transporter activity • phosphatidylcholine binding • lipid binding • phospholipid transporter activity Cellular component • cytoplasm • cytosol Biological process • phospholipid transport • lipid transport • phosphatidylcholine biosynthetic process • negative regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	58488	18559
Ensembl	ENSG00000141179	ENSMUSG00000020553
UniProt	Q9UKL6	P53808 Q5SV41
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: 89.98 – 90 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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]

References

1. GRCh38: Ensembl release 89: ENSG00000141179 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020553 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. van Golde LM, Oldenborg V, Post M, Batenburg JJ, Poorthuis BJ, Wirtz KW (July 1980). "Phospholipid transfer proteins in rat lung. Identification of a protein specific for phosphatidylglycerol". J. Biol. Chem. 255 (13): 6011–3. PMID 7391000.
6. Wirtz KW (July 1991). "Phospholipid transfer proteins". Annu. Rev. Biochem. 60 (13): 73–99. doi:10.1146/annurev.bi.60.070191.000445. PMID 1883207.
7. "Entrez Gene: phosphatidylcholine transfer protein".
8. van Helvoort A, de Brouwer A, Ottenhoff R, Brouwers JF, Wijnholds J, Beijnen JH, Rijneveld A, van der Poll T, van der Valk MA, Majoor D, Voorhout W, Wirtz KW, Elferink RP, Borst P (September 1999). "Mice without phosphatidylcholine transfer protein have no defects in the secretion of phosphatidylcholine into bile or into lung airspaces". Proc. Natl. Acad. Sci. U.S.A. 96 (20): 11501–6. doi:10.1073/pnas.96.20.11501. PMC 18063. PMID 10500206.
9. Kanno K, Wu MK, Agate DA, Fanelli BK, Wagle N, Scapa EF, Ukomadu C, Cohen DE (October 2007). "Interacting proteins dictate function of the minimal START domain phosphatidylcholine transfer protein/StarD2". J. Biol. Chem. 282 (42): 30728–36. doi:10.1074/jbc.M703745200. PMID 17704541.
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.
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.
15. Scapa EF, Pocai A, Wu MK, Gutierrez-Juarez R, Glenz L, Kanno K, Li H, Biddinger S, Jelicks LA, Rossetti L, Cohen DE (July 2008). "Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2". FASEB J. 22 (7): 2579–90. doi:10.1096/fj.07-105395. PMID 18347010. S2CID 19224763.

External links

• Overview of all the structural information available in the PDB for UniProt: Q9UKL6 (Phosphatidylcholine transfer protein) at the PDBe-KB.