PITPNM3
Description
The PITPNM3 (PITPNM family member 3) is a protein-coding gene located on chromosome 17.
Nir1 or membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3) is a mammalian protein that localizes to endoplasmic reticulum (ER) and plasma membrane (PM) membrane contact sites (MCS) and aids the transfer of phosphatidylinositol between these two membranes, potentially by recruiting additional proteins to the ER-PM MCS. It is encoded by the gene PITPNM3.
== Classification == Nir1 has been classically categorized as a class IIA phosphatidylinositol transfer protein (PITP) that transfers phosphatidylinositol (PI) and phosphatidic acid (PA) between membranes. Class IIA PITPs are the multi-domain proteins PITPNM1/Nir2 (Drosophila homolog RdgBaI), PITPNM2/Nir3 (Drosophila homolog RdgBaII).. Nir1 shares high sequence similarity with Nir2 and Nir3, which led to its original categorization as a PITP. However, it was determined that Nir1 is not directly responsible for PI transfer, as it lacks the functional PITP domain seen within Nir2 and Nir3
== Localization == Recently, Nir1 has been shown to localize to ER-PM MCS, both under basal conditions and upon phospholipase C (PLC) activation. Notably, PLC activation has previously been shown to regulate the localization of Nir2 and Nir3 at ER-PM MCS well.. The MCS-targeting by Nir1 is achieved by the N-terminus of Nir1 localizing to the ER and the C-terminus of Nir1 localizing to the PM. The domains responsible for binding these membranes are discussed below.
== Structure == Nir1 contains three main structural elements that are shared with Nir2 and Nir3: an N-terminal FFAT motif, a DDHD domain, and a C-terminal Lipin/Ndel/Smp2 (LNS2) domain.
=== FFAT motif === The FFAT motif is made up of double phenylalanines (FF) in an Acidic Tract. This motif, made of residues EFFDA in Nir1, has been shown to be necessary for the Nir proteins to associate with the ER proteins VAPA and VAPB. Mutation of the phenylalanine residues in this motif or knockout of the VAPA and VAPB proteins results in a loss of ER-PM MCS localization and causes Nir1 to become fully localized to the PM.
=== DDHD domain === The DDHD domain, made up of 3 Asp and 1 His residues, bears some similarities to that seen in PLA1 enzymes, which hydrolyze fatty acids of glycerolphospholipids, including phosphatidic acid (PA). However, this domain is still largely uncharacterized.
PITPNM3 is also known as ACKR6, CORD5, NIR1, RDGBA3.
