Phosphatidylinositol transfer protein
Encyclopedia
Phosphatidylinositol transfer protein (PITP) or priming in exocytosis protein 3 (PEP3) is a ubiquitous cytosolic domain involved in transport of phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

s from their site of synthesis in the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 and Golgi
Golgi
Golgi may refer to:*Camillo Golgi , Italian physician and scientist after which the following terms are named:**Golgi apparatus , an organelle in the eukaryotic cell...

 to other
cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

s.

Biological function

PITP has been also shown to be an essential component of the polyphosphoinositide synthesis machinery and is hence required for proper signalling by epidermal growth factor
Epidermal growth factor
Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR...

 and f-Met-Leu-Phe, as well as for exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...

. The role of PITP in polyphosphoinositide synthesis may also explain its involvement in intracellular vesicular traffic.

Structure and evolution

Along with the structurally unrelated Sec14p family (found in ), this family can bind/exchange one molecule of phosphatidylinositol (PI) or phosphatidylcholine (PC) and thus aids their transfer between different membrane compartments. There are three sub-families - all share an N-terminal PITP-like domain, whose sequence is highly conserved. It is described as consisting of three regions. The N-terminal region is thought to bind the lipid and contains two helices and an eight-stranded, mostly antiparallel beta-sheet. An intervening loop region, which is thought to play a role in protein-protein interactions, separates this from the C-terminal region, which exhibits the greatest sequence variation and may be involved in membrane binding. This motif marks PITP as part of the larger SRPBCC (START
StAR-related transfer 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 and initiates steroid production by mediating the delivery of cholesterol to the first enzyme in...

/RHOalphaC/PITP/Bet v1
Bet v I allergen
Bet v I allergen is a family of protein allergens. Allergies are hypersensitivity reactions of the immune system to specific substances called allergens that, in most people, result in no symptoms....

/CoxG/CalC) domain superfamily.

PITP alpha (UniProt
UniProt
UniProt is a comprehensive, high-quality and freely accessible database of protein sequence and functional information, many of which are derived from genome sequencing projects...

 ) has a 16-fold greater affinity for PI than PC. Together with PITP beta (UniProt ), it is expressed ubiquitously in all tissues.

Human proteins

The family of human phosphatidylinositol transfer proteins has several members:
  • Phosphatidylinositol transfer protein, alpha
    Phosphatidylinositol transfer protein, alpha
    Phosphatidylinositol transfer protein alpha isoform is a protein that in humans is encoded by the PITPNA gene.-Further reading:...

     (PITPNA)
  • Phosphatidylinositol transfer protein, beta (PITPNB)
  • Phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC)
  • Phosphatidylinositol transfer protein, membrane-associated 1 (PITPNM1)
  • Phosphatidylinositol transfer protein, membrane-associated 2 (PITPNM2)
  • PITPNM family member 3 (PITPNM3)
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