Phosphatidylinositol transfer protein

Phosphatidylinositol transfer protein, beta isoform
Identifiers
Symbol	IP_trans
Pfam	PF02121
InterPro	IPR001666
SCOP2	1fvz / SCOPe / SUPFAM
OPM superfamily	138
OPM protein	2a1l
CDD	cd07815
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Phosphatidylinositol transfer protein (PITP) or priming in exocytosis protein 3 (PEP3) is a ubiquitous cytosolic domain involved in transport of phospholipids from their site of synthesis in the endoplasmic reticulum and Golgi to other cell membranes.[1][2]

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 and f-Met-Leu-Phe, as well as for exocytosis. The role of PITP in polyphosphoinositide synthesis may also explain its involvement in intracellular vesicular traffic.[1]

Structure and evolution

Along with the structurally unrelated Sec14p family (found in Pfam PF00650), 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/RHOalphaC/PITP/Bet v1/CoxG/CalC) domain superfamily.^[citation needed]

PITP alpha (UniProt Q00169) has a 16-fold greater affinity for PI than PC. Together with PITP beta (UniProt P48739), it is expressed ubiquitously in all tissues.[3]

Human proteins

The family of human phosphatidylinositol transfer proteins has several members:

• Phosphatidylinositol transfer protein, alpha (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)

References

1. Liscovitch M, Cantley LC (1995). "Signal transduction and membrane traffic: the PITP/phosphoinositide connection". Cell. 81 (5): 659–662. doi:10.1016/0092-8674(95)90525-1. PMID 7774006.
2. Hay JC, Martin TF (December 1993). "Phosphatidylinositol transfer protein required for ATP-dependent priming of Ca(2+)-activated secretion". Nature. 366 (6455): 572–5. Bibcode:1993Natur.366..572H. doi:10.1038/366572a0. PMID 8255295. S2CID 4348488.
3. Hsuan J, Cockcroft S (2001). "The PITP family of phosphatidylinositol transfer proteins". Genome Biol. 2 (9): REVIEWS3011. doi:10.1186/gb-2001-2-9-reviews3011. PMC 138965. PMID 11574064.

This article incorporates text from the public domain Pfam and InterPro: IPR001666