MBOAT1

Model summary

A multi-pass endoplasmic reticulum membrane acyltransferase that uses a membrane-embedded catalytic center to transfer acyl groups from acyl-CoA donors onto lysophospholipids, thereby generating diacylated products that feed phosphatidylcholine and phosphatidylserine pathways. By executing lysophospholipid acyl editing within the ER bilayer, it supports membrane phospholipid homeostasis and coordinates with other ER lipid enzymes to tune acyl composition during phospholipid metabolism.

Predicted Gene Ontology terms

1. 01

   I begin with the InterPro architecture.

   The polypeptide carries IPR049941 (Lysophospholipid acyltransferase 7/Porcupine-like family) spanning residues 17–480, which frames the entire catalytic core and establishes membership in the LPLAT7/Porcupine-like clade of membrane acyltransferases. Nested within this scaffold is IPR004299 (Membrane bound O-acyl transferase, MBOAT family) from residues 126–436. The MBOAT core defines a multi-pass membrane enzyme that uses a membrane-embedded catalytic center—typically a conserved histidine within a luminal/periplasmic loop—to transfer acyl groups from acyl-CoA donors to hydrophobic acceptors. The ordered layout—an extensive LPLAT7/Porcupine-like envelope containing a central MBOAT catalytic module—causally dictates an O-acyltransferase chemistry executed within the endoplasmic reticulum membrane.

2. 02

   This MBOAT-centered architecture specifies molecular function.

   The catalytic cavity of MBOATs positions acyl-CoA and lysophospholipid acceptors within the bilayer, enabling acyl transfer to form diacyl phospholipids. That chemistry corresponds to GO:0042171 lysophosphatidic acid acyltransferase activity and GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity, because the same acyltransferase logic underlies both LPAAT and LPLAT reactions. The LPLAT7/Porcupine-like family context further narrows substrate scope toward lysophospholipids and acyl-CoA pairs, consistent with selective acyl editing of membrane lipids.

3. 03

   From function to process, acyl editing of lysophospholipids feeds directly into glycerophospholipid remodeling pathways that set the acyl composition of bulk membrane phospholipids.

   This acylation step supplies diacylated intermediates and products that drive GO:0046470 phosphatidylcholine metabolic process and GO:0006658 phosphatidylserine metabolic process. By channeling acyl flux into PC and PS branches, the enzyme supports membrane biogenesis and signaling lipid homeostasis.

4. 04

   Cellular location follows from the transmembrane MBOAT core and the need to access nascent phospholipids and acyl-CoA pools.

   The multi-pass topology and ER-resident biosynthetic role place the enzyme in the GO:0005789 endoplasmic reticulum membrane, where glycerophospholipid assembly and remodeling are concentrated.

5. 05

   Mechanistically, the MBOAT catalytic chamber likely binds acyl-CoA on the cytosolic face, relays the acyl chain through a membrane-accessible tunnel, and transfers it to lysophospholipid acceptors within the ER bilayer.

   This acyl-editing mechanism explains its role in tuning PC and PS pools and suggests partnerships with other ER lipid enzymes. I hypothesize transient assemblies with ER acyltransferases and remodeling factors—such as LPCATs and LPCAT3—along with acyl-CoA–handling systems (e.g., long-chain acyl-CoA synthetases) and phospholipid biosynthetic nodes (e.g., CEPT1 and the phosphatidylcholine pathway). These complexes would coordinate substrate channeling and maintain balanced acyl profiles across ER membranes.