PITPNM1,2,3 exchange PI for PA

Stable Identifier
Reaction [transition]
Homo sapiens
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Phosphatidylinositol 4,5-bisphosphate (PIP2) at the plasma membrane (PM) constitutively controls many cellular functions, and its hydrolysis via receptor stimulation can mediate cell signalling. A steady delivery of phosphatidylinositol (PI) from its site of synthesis in the endoplasmic reticulum (ER) to the PM is essential to maintain PIP2 levels. In addition, phosphatidic acid (PA), generated from diacylglycerol in the PM, has to reach the ER for PI resynthesis. The ubiquitously-expressed membrane-associated phosphatidylinositol transfer proteins 1, 2 and 3 (PITPNM1,2,3) (Lev et al. 1999) detect PIP2 hydrolysis and translocate to ER-PM junctions where they mediate the exchange of PI for PA (Kim et al. 2015, Chang & Liou 2015). Defects in PITPNM3 can cause cone-rod dystrophy 5 (CORD5; MIM:600977), a retinal dystrophy manifested as progressive loss of central vision, defective color vision, and photophobia. The missense mutation Q626H lacks the N-terminal PIT domain needed for transport of phospholipids and renewal of photoreceptors membranes is impaired (Kohn et al. 2007).
Literature References
PubMed ID Title Journal Year
17377520 Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families

Sandgren, O, Haraldsson, S, Burstedt, MS, Köhn, L, Kadzhaev, K, Hallberg, B, Golovleva, I

Eur. J. Hum. Genet. 2007
10022914 Identification of a novel family of targets of PYK2 related to Drosophila retinal degeneration B (rdgB) protein

Schlessinger, J, Chen, A, Lev, S, Plowman, G, Hernandez, J, Martinez, R

Mol. Cell. Biol. 1999
26028218 Phosphatidylinositol-Phosphatidic Acid Exchange by Nir2 at ER-PM Contact Sites Maintains Phosphoinositide Signaling Competence

Balla, T, Wisniewski, E, Kim, YJ, Guzman-Hernandez, ML

Dev. Cell 2015
25887399 Phosphatidylinositol 4,5-Bisphosphate Homeostasis Regulated by Nir2 and Nir3 Proteins at Endoplasmic Reticulum-Plasma Membrane Junctions

Chang, CL, Liou, J

J. Biol. Chem. 2015
Catalyst Activity

phosphatidylinositol transfer activity of PITPNM1,2,3 [cytosol]

Orthologous Events
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