| Tissue Specificity | Widely expressed. In the brain, high levels of expression are detected in the frontal, temporal and occipital cortices and hippocampus. Expressed at low level in corpus callosum. Expressed in plasmacytoid dendritic cells and monocytes (at protein level). |
| Post Translational Modifications | N-glycosylated. Proteolytically processed to a soluble active form that is stable within endosomes and lysosomes. During transport through the secretory pathway becomes proteolysed by cysteine proteases, thereby releasing a stable soluble lysosomal lumenal polypeptide, whereas the transmembrane-bound fragment is rapidly degraded. Its transport route to lysosomes involves ubiquitination and the ESCRT complex. Ubiquitinated at N-terminus. Ubiquitination mediates sorting into lysosomes. |
| Function | 5'->3' exonuclease that hydrolyzes the phosphodiester bond of single-stranded DNA (ssDNA) and RNA molecules to form nucleoside 3'-monophosphates and 5'-end 5'-hydroxy deoxyribonucleotide/ribonucleotide fragments. Partially redundant with PLD4, can cleave all four nucleotides displaying higher efficiency for ssDNA and RNA fragments initiated with uridine and guanosine residues and lower efficiency for cytidine-initiated substrates. As a result, it does not always degrade polynucleotides to the single nucleotide level, it can stall at specific sites sparing certain fragments from exonucleolytic degradation. Processes self and pathogenic ssDNA and RNA molecules that reach the endolysosomal compartment via phagocytosis or autophagy and may serve as 'danger' signals for recognition by innate immune receptors such as toll-like receptors (TLRs). Degrades mitochondrial CpG-rich ssDNA fragments to prevent TLR9 activation and autoinflammatory response, but it can cleave viral RNA to generate ligands for TLR7 activation and initiate antiviral immune responses. In plasmacytoid dendritic cells, it cooperates with endonuclease RNASET2 to release 2',3'-cyclic guanosine monophosphate (2',3'-cGMP), a potent stimulatory ligand for TLR7. Produces 2',3'-cGMPs and cytidine-rich RNA fragments that occupy TLR7 ligand-binding pockets and trigger a signaling-competent state. Can exert polynucleotide phosphatase activity toward 5'-phosphorylated ssDNA substrates although at a slow rate. Transphosphatidylase that catalyzes the exchange with R to S stereo-inversion of the glycerol moiety between (S,R)-lysophosphatidylglycerol (LPG) and monoacylglycerol (MAG) substrates to yield (S,S)-bis(monoacylglycero)phosphate (BMP). Can synthesize a variety of (S,S)-BMPs representing the main phospholipid constituent of lysosomal intralumenal vesicle (ILV) membranes that bind acid hydrolases for lipid degradation. Regulates the homeostasis and interorganellar communication of the endolysosomal system with an overall impact on cellular removal of dysfunctional organelles via autophagy as well as proper protein and lipid turnover. May play a role in myotube formation in response to ER stress. |
| Protein Name | 5'-3' Exonuclease Pld3(S -S-Bis(Monoacylglycerophosphate Synthase Pld3Hindiii K4l HomologHu-K4Phospholipase D3 |
| Database Links | Reactome: R-HSA-1483148Reactome: R-HSA-2029485 |
| Cellular Localisation | Endoplasmic Reticulum MembraneSingle-Pass Type Ii Membrane ProteinLysosome LumenEarly Endosome MembraneLate Endosome MembraneGolgi Apparatus MembraneEndosome MembraneLocalizes To Er-Associated Vesicles In Differentiating MyotubesSorted Into Intralumenal Vesicles (Ilvs) In LysosomesThe Soluble Form In Lysosome Arises By Proteolytic Processing Of The Membrane-Bound FormColocalizes With App In Endosomes |
| Alternative Antibody Names | Anti-5'-3' Exonuclease Pld3 antibodyAnti-(S -S-Bis(Monoacylglycerophosphate Synthase Pld3 antibodyAnti-Hindiii K4l Homolog antibodyAnti-Hu-K4 antibodyAnti-Phospholipase D3 antibodyAnti-PLD3 antibody |
Information sourced from Uniprot.org
