Affinage

PLIN3

Perilipin-3 · UniProt O60664

Length
434 aa
Mass
47.1 kDa
Annotated
2026-06-10
59 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLIN3 (TIP47/M6PRBP1) is a PAT/perilipin-family protein that partitions between the cytosol and the surface of lipid droplets in response to the cellular lipid load, functioning in lipid droplet biogenesis, triglyceride storage, and lipid trafficking (PMID:11084026, PMID:19451273, PMID:19748893). It is recruited to nascent droplets that emerge along the endoplasmic reticulum when membranes become enriched in diacylglycerol, and blocking conversion of diacylglycerol to triacylglycerol by DGAT1 attenuates this recruitment, coupling PLIN3 membrane association to metabolic state (PMID:15731108, PMID:19748893). The protein has a bipartite architecture: an N-terminal 11-mer repeat region with apolipoprotein-like properties that reorganizes liposomes into lipid discs and drives droplet recruitment, and a C-terminal four-helix bundle structurally resembling the LDL-receptor-binding domain of apolipoprotein E (PMID:15242596, PMID:19451273, PMID:22508559). Suppression of PLIN3 blocks lipid-droplet maturation and shifts fatty-acid utilization away from triglyceride storage, and in vivo knockdown reduces hepatic triglyceride content, steatosis, and triglyceride secretion while improving insulin sensitivity (PMID:16968708, PMID:19451273, PMID:22378776). PLIN3 also serves as a platform for lipid-droplet turnover, acting downstream of mTORC1 phosphorylation as a docking protein that binds the autophagy machinery ATG16L and FAK200 to drive lipophagy (PMID:34233024). Independently of its lipid role, PLIN3 was originally characterized as a selective binder of the cytoplasmic tails of the cation-independent and cation-dependent mannose-6-phosphate receptors and of GTP-bound Rab9, with Rab9 binding enhancing MPR-tail affinity through a domain distinct from the MPR-binding site (PMID:9590177, PMID:11359012, PMID:10829017, PMID:12032303); however, a later study found PLIN3 knockdown had no effect on MPR distribution or lysosomal enzyme sorting, leaving the physiological weight of the endosome-to-TGN transport role unsettled (PMID:19451273). PLIN3 is additionally co-opted by viruses, binding HCV NS5A through its N-terminal PAT domain to support viral RNA replication and particle release, and bridging HIV-1 Gag and Env to promote Env incorporation, although the requirement for HIV Env incorporation is cell-type dependent (PMID:23593007, PMID:23354285, PMID:17003132, PMID:23325685).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1998 High

    Established the founding biochemical activity of PLIN3 as a cytosolic recognition factor for mannose-6-phosphate receptor tails required for their retrograde endosome-to-TGN transport, defining a membrane-trafficking function before any lipid role was known.

    Evidence In vitro reconstituted transport assay plus in vivo functional studies and selective binding to MPR cytoplasmic domains

    PMID:9590177

    Open questions at the time
    • Did not establish how recruitment to endosomes is regulated
    • Physiological necessity later challenged by knockdown showing no MPR sorting defect
  2. 2000 High

    Quantified cargo selectivity, showing PLIN3 binds CI-MPR and CD-MPR tails with micromolar affinity but ignores furin, carboxypeptidase D, and TGN38 tails, establishing specific signal recognition.

    Evidence Quantitative binding assays with recombinant proteins and specificity controls

    PMID:10829017

    Open questions at the time
    • Did not define the structural basis of the diaromatic-signal recognition
  3. 2001 High

    Defined PLIN3 as a Rab9-GTP effector and showed that active Rab9 binding increases its affinity for MPR tails, linking a Rab GTPase switch to cargo capture.

    Evidence Direct pulldown binding assays, mutagenesis, and in vivo transport assays

    PMID:11359012

    Open questions at the time
    • Mechanism by which Rab9 allosterically raises MPR affinity not resolved structurally
  4. 2002 High

    Mapped the Rab9-binding determinant (residues 161-169) and demonstrated it is structurally and functionally separable from the MPR-binding site, establishing modular domain organization.

    Evidence Site-directed mutagenesis, binding assays, circular dichroism, partial proteolysis

    PMID:12032303

    Open questions at the time
    • Region is necessary but not sufficient for Rab9 binding; full interface undefined
  5. 2000 Medium

    Revealed a second life for PLIN3 by showing lipid-load-dependent redistribution from cytosol to lipid droplets, first connecting it to lipid storage organelles.

    Evidence Immunofluorescence, subcellular fractionation, and Western blotting under fatty-acid supplementation

    PMID:11084026

    Open questions at the time
    • Targeting determinant not identified
    • Early antibody specificity concerns noted
  6. 2003 High

    Showed PLIN3 forms cytosolic oligomers (~hexamers) via an N-terminal domain (1-151) and that oligomerization, while dispensable for MPR binding, is required for stimulating MPR transport, separating binding from function.

    Evidence Gel filtration, chemical cross-linking, deletion mutagenesis, and in vivo transport assay

    PMID:12535272

    Open questions at the time
    • Relationship between oligomerization and lipid-droplet function not addressed
  7. 2003 High

    Extended the trafficking-adaptor role to viral biology, showing the HIV-1 gp41 cytoplasmic tail binds PLIN3 through a Y802W803 diaromatic motif to drive Env retrograde transport and efficient virion incorporation.

    Evidence Co-immunoprecipitation, internalization assays, dominant-negative overexpression, and mutagenesis with infectivity readout

    PMID:12768012

    Open questions at the time
    • Did not test requirement across cell types
    • Later contradicted in HeLa/Jurkat
  8. 2004 High

    Provided the structural framework by solving the C-terminal domain, revealing a four-helix bundle resembling apolipoprotein E and explaining how a PAT protein could engage lipid surfaces like an apolipoprotein.

    Evidence X-ray crystallography at 2.8 Å of residues ~180-434

    PMID:15242596

    Open questions at the time
    • N-terminal repeat region not crystallized
    • Lipid-bound conformation unknown
  9. 2005 Medium

    Established PLIN3 as a coat protein of nascent lipid droplets drawn from a preexisting cytosolic reservoir, showing oleate-driven recruitment is independent of new protein synthesis.

    Evidence Immunofluorescence, subcellular fractionation, and cycloheximide inhibition in adipocytes

    PMID:15731108

    Open questions at the time
    • Did not define the signal sensed during recruitment
  10. 2006 Medium

    Demonstrated PLIN3's role in triglyceride storage and droplet formation, showing knockdown reduces droplets and diverts fatty acids toward phospholipids, and that PLIN3 and ADRP use distinct targeting mechanisms.

    Evidence siRNA knockdown in ADFP-null cells, lipid droplet imaging, deletion mutagenesis, Rab18 overexpression, and mass spectrometry

    PMID:16808905 PMID:16968708

    Open questions at the time
    • Functional redundancy with other perilipins complicates interpretation
  11. 2006 High

    Showed reciprocal regulation between PLIN3 and Rab9 localization and that PLIN3 bridges HIV-1 Gag and Env in a ternary complex required for Env incorporation, broadening its adaptor function.

    Evidence Rab chimera localization studies; Co-IP, siRNA, overexpression, and infectivity assays

    PMID:16769818 PMID:17003132

    Open questions at the time
    • HIV requirement not yet tested across cell types
  12. 2006 Medium

    Identified a lipase-regulatory role, showing PLIN3 inhibits retinylester hydrolysis by GS2 and hormone-sensitive lipase via its C-terminal helices, linking droplet coating to controlled lipid hydrolysis.

    Evidence cDNA library screen, deletion mutagenesis, and enzyme activity assays in keratinocytes

    PMID:16741517

    Open questions at the time
    • Direct enzyme-PLIN3 contact not demonstrated
    • Single in vitro system
  13. 2009 High

    Reframed the dominant function of PLIN3 as a lipid-droplet biogenesis factor, identifying the N-terminal 11-mer repeats as the recruitment element with apolipoprotein-like membrane-reorganizing activity, while arguing against an MPR-sorting role.

    Evidence siRNA knockdown, fluorescence microscopy, in vitro liposome reorganization assay, and lipid analysis

    PMID:19451273

    Open questions at the time
    • Directly contradicts the earlier MPR transport model; reconciliation unresolved
    • Discrepancy with #12 over which half targets droplets
  14. 2009 High

    Linked PLIN3 membrane association to metabolic state, showing diacylglycerol enrichment of ER/droplet membranes recruits PLIN3 and that DGAT1-mediated conversion to triacylglycerol attenuates recruitment.

    Evidence Fluorescence microscopy with pharmacological and genetic perturbations and lipid fractionation

    PMID:19748893

    Open questions at the time
    • Molecular sensor of diacylglycerol on PLIN3 not identified
  15. 2010 Medium

    Identified a cytoprotective, mitochondria-associated activity, showing PLIN3 translocates to mitochondria under oxidative stress and preserves membrane potential, an unexpected role beyond lipid droplets.

    Evidence Overexpression, siRNA, JC1 assay, recombinant protein in vitro, and immunolocalization

    PMID:20556887

    Open questions at the time
    • Mechanism of mitochondrial action unknown
    • Single lab, not independently confirmed
  16. 2012 Medium

    Established the in vivo metabolic relevance of hepatic PLIN3, showing its reduction lowers liver triglycerides and steatosis while improving systemic insulin sensitivity.

    Evidence Antisense oligonucleotide knockdown in mice with histology, triglyceride measurement, and glucose/insulin tolerance tests

    PMID:22378776

    Open questions at the time
    • Tissue-specific contributions not isolated
    • Mechanism connecting droplets to insulin sensitivity not defined
  17. 2012 Medium

    Showed full-length PLIN3 adopts an extended solution conformation with a predominantly β-structured N-terminus separated from the helical C-terminal bundle, supporting functional domain separation.

    Evidence Small-angle X-ray scattering and N-terminal truncation analysis

    PMID:22508559

    Open questions at the time
    • No functional mutagenesis validation
    • Low-resolution model only
  18. 2013 High

    Established PLIN3 as an HCV host factor, showing N-terminal PAT-domain binding to NS5A and viral RNA is required for replication and particle release, with Rab9 binding directing particles to release rather than lysosomal degradation.

    Evidence Yeast two-hybrid, Co-IP, shRNA/siRNA knockdown, subgenomic replicon, mutagenesis, membrane flotation, and immunogold EM

    PMID:23354285 PMID:23593007 PMID:24480419

    Open questions at the time
    • Whether PLIN3 acts through its lipid-droplet function or as a direct scaffold not fully separated
  19. 2013 Medium

    Refined the HIV model by showing the PLIN3-Gag/Env interaction is required in primary macrophages but dispensable in HeLa and Jurkat cells, establishing cell-type dependence of the viral role.

    Evidence siRNA, mutagenesis, Co-IP, colocalization, infectivity assays; NMR and SPR confirming MA binding

    PMID:20070608 PMID:23325685

    Open questions at the time
    • Basis of cell-type dependence unexplained
    • Physical interaction confirmed but functional requirement context-specific
  20. 2013 Medium

    Connected PLIN3 to lipid-droplet-dependent inflammatory lipid mediator production, showing knockdown abolishes droplet formation and reduces PGE2 secretion and prostaglandin enzyme expression in neutrophils.

    Evidence siRNA knockdown, immunofluorescence, droplet quantification, PGE2 ELISA, Western blotting

    PMID:23936516

    Open questions at the time
    • Mechanism linking droplets to enzyme expression unclear
    • Single cell model
  21. 2019 Medium

    Identified a cytoskeletal and ER-protective role, showing PLIN3 links droplets to microtubules via dynein subunit Dync1i1 and promotes lipid export from the ER to limit lipotoxic stress.

    Evidence Co-IP, immunofluorescence colocalization, siRNA, triglyceride measurement, and ER stress markers

    PMID:31119787

    Open questions at the time
    • Direct vs indirect dynein interaction not resolved
    • Mechanism of ER lipid export unknown
  22. 2021 Medium

    Defined PLIN3 as a regulated platform for lipophagy and a target of metabolic regulation, showing mTORC1 phosphorylates PLIN3 to drive autophagic droplet degradation via ATG16L/FAK200 docking, and that ACSS3 controls PLIN3 protein stability to tune droplet accumulation.

    Evidence siRNA, Co-IP, phosphorylation assays, in vitro/in vivo/ex vivo lipophagy assays; and Co-IP, Western, Oil Red O, LC/MS in prostate cancer cells

    PMID:33391508 PMID:34233024

    Open questions at the time
    • Phosphosites and their direct effect on autophagy-protein binding not mapped
    • ACSS3-mediated degradation pathway not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PLIN3's original MPR/Rab9 trafficking function is reconciled with its dominant lipid-droplet role, and what molecular feature dictates context- and cell-type-specific requirements, remain unresolved.
  • No unifying model explaining both MPR-binding and lipid-droplet functions
  • No structure of the lipid- or NS5A-bound N-terminal repeat region
  • Mechanism of diacylglycerol sensing during membrane recruitment unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005811 lipid droplet 4 GO:0005829 cytosol 3 GO:0005768 endosome 2 GO:0005783 endoplasmic reticulum 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-9609507 Protein localization 2 R-HSA-9612973 Autophagy 1
Partners
ACSS3ATG16L1DYNC1I1IGF2RNS5ARAB9A

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 TIP47/PLIN3 binds selectively to the cytoplasmic domains of both cation-independent and cation-dependent mannose 6-phosphate receptors (MPRs) and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo; it recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR essential for proper endosomal sorting. Biochemical binding assays, in vitro transport assay, in vivo functional studies Cell High 9590177
2001 TIP47/PLIN3 binds directly to the active (GTP-bound) form of Rab9 GTPase, and Rab9 binding increases TIP47 affinity for MPR cytoplasmic domains; a functional Rab9 binding site on TIP47 is required for stimulation of MPR transport in vivo. Direct binding assays (pulldown), in vivo transport assays, mutagenesis Science High 11359012
2000 Recombinant TIP47/PLIN3 binds the cation-independent MPR cytoplasmic domain with Kd ~1 µM and the cation-dependent MPR with Kd ~3 µM, but fails to interact with furin, phosphorylated furin, metallocarboxypeptidase D, or TGN38 cytoplasmic domains, demonstrating highly selective cargo recognition. Quantitative binding assays with recombinant proteins The Journal of biological chemistry High 10829017
2000 TIP47/PLIN3 associates with lipid droplets in a lipid-load-dependent manner: under low lipid conditions TIP47 is primarily cytosolic, but upon fatty acid supplementation a significant fraction redistributes to lipid droplet fractions in HeLa and MA10 Leydig cells. Immunofluorescence microscopy, subcellular fractionation, Western blotting The Journal of biological chemistry Medium 11084026
2002 TIP47/PLIN3 residues 161–169 are essential (but not sufficient) for Rab9 binding; mutations in this region decrease Rab9 binding without altering global protein folding or MPR binding capacity, demonstrating that Rab9 and MPR binding involve distinct domains. Site-directed mutagenesis, binding assays, circular dichroism, partial proteolysis Proceedings of the National Academy of Sciences of the United States of America High 12032303
2002 GFP-tagged TIP47/PLIN3 co-localizes with isolated intracellular lipid droplets, and antibodies specifically recognizing TIP47 label lipid droplet surfaces, demonstrating conserved lipid droplet association across PAT family members from mammals, Drosophila, and Dictyostelium. GFP co-localization, immunofluorescence with specific antibodies, lipid droplet isolation The Journal of biological chemistry Medium 12077142
2003 TIP47/PLIN3 exists as oligomers (~300 kDa, ~13S) in cytosol, likely hexamers by chemical cross-linking; the N-terminal residues 1–151 contain the oligomerization domain. Oligomerization is not required for MPR binding but is required for TIP47 stimulation of MPR transport from endosomes to the trans-Golgi in vivo. Gel filtration, chemical cross-linking, co-expression studies, deletion mutagenesis, in vivo transport assay Traffic High 12535272
2004 The crystal structure of the C-terminal domain of TIP47/PLIN3 (residues ~180–434) was solved at 2.8 Å resolution, revealing an α/β domain of novel topology and a four-helix bundle resembling the LDL receptor binding domain of apolipoprotein E, suggesting PAT proteins share structural analogy with apolipoproteins. X-ray crystallography Structure High 15242596
2003 The cytoplasmic domain of HIV-1 gp41 binds TIP47/PLIN3 through a Y802W803 diaromatic motif; this interaction mediates retrograde transport of Env from endosomes to the TGN; mutation of the YW motif abolishes TGN targeting, TIP47 interaction, and results in poor Env incorporation into virions and reduced infectivity. Co-immunoprecipitation, internalization assays, overexpression of dominant-negative TIP47 mutant, mutagenesis Journal of virology High 12768012
2005 S3-12, TIP47/PLIN3, and adipophilin coat nascent lipid droplets that emerge upon oleate treatment of adipocytes; oleate drives redistribution of TIP47 and adipophilin from cytosolic fractions to the lipid droplet fraction; this redistribution occurs independently of new protein synthesis, indicating a ready cytosolic reservoir of coat proteins. Immunofluorescence, subcellular fractionation, cycloheximide inhibition experiments The Journal of biological chemistry Medium 15731108
2006 TIP47/PLIN3 acts as a connector between HIV-1 Gag (matrix domain) and Env glycoprotein, forming a ternary complex; Gag mutations abrogating TIP47 interaction inhibit Env incorporation and virion infectivity; TIP47 silencing impairs Env incorporation; TIP47 overexpression increases Env packaging. Co-immunoprecipitation, siRNA knockdown, overexpression, colocalization studies, infectivity assays Proceedings of the National Academy of Sciences of the United States of America High 17003132
2006 TIP47/PLIN3 is a key effector for Rab9 localization: changing the cellular concentration of TIP47 shifts chimeric Rab5/9 or Rab1/9 proteins toward Rab9 localization, demonstrating that effector concentration influences Rab steady-state localization. Rab chimera localization studies, overexpression/modulation of TIP47 concentration, fluorescence microscopy The Journal of cell biology Medium 16769818
2006 The C-terminal half of TIP47/PLIN3, specifically the putative hydrophobic cleft, is required for lipid droplet targeting and responsiveness to fatty acids; deletion of the C-terminal half abolishes LD targeting; TIP47 and ADRP have distinct LD-targeting mechanisms since Rab18 overexpression removes ADRP but not TIP47 from LDs. Deletion mutagenesis, immunofluorescence, Rab18 overexpression, siRNA knockdown of ADRP Biochemical and biophysical research communications Medium 16808905
2006 TIP47/PLIN3 knockdown by siRNA in ADFP-null cells reduces lipid droplet formation and shifts utilization of exogenous fatty acids from triglycerides toward phospholipids, demonstrating a role in triglyceride storage and lipid droplet metabolism when ADRP is absent. siRNA knockdown, lipid droplet imaging, lipid metabolic measurements, mass spectrometry The Journal of biological chemistry Medium 16968708
2009 TIP47/PLIN3 knockdown had no effect on MPR distribution, trafficking, or lysosomal enzyme sorting, arguing against a role as an MPR sorting device; instead, TIP47 is recruited to lipid droplets by an N-terminal sequence comprising 11-mer repeats, has apolipoprotein-like properties, reorganizes liposomes into small lipid discs, and its suppression blocks LD maturation and decreases triacylglycerol incorporation into LDs. siRNA knockdown, fluorescence microscopy, in vitro liposome reorganization assay, lipid analysis The Journal of cell biology High 19451273
2009 Perilipin 3/TIP47-coated lipid droplets emerge along the endoplasmic reticulum; diacylglycerol (DG) enrichment of ER or lipid droplet membranes recruits PLIN3 to these membranes; blocking DG conversion to triacylglycerol (via DGAT1) attenuates this recruitment, linking PLIN3 membrane association to the metabolic state of the cell. Fluorescence microscopy, pharmacological manipulation (AlF4-, forskolin, DG lipase inhibitor, triacsin C), DGAT1 overexpression, lipid fractionation The Journal of biological chemistry High 19748893
2009 TIP47/PLIN3 protein levels directly correlate with triglyceride levels in macrophages: siRNA knockdown decreases triglycerides while EGFP-TIP47 overexpression increases them; TIP47 is present in the plasma membrane of macrophages and clusters upon oleate treatment. siRNA knockdown, EGFP overexpression, freeze-fracture cytochemistry, triglyceride measurement Arteriosclerosis, thrombosis, and vascular biology Medium 19286631
2010 TIP47/PLIN3 silencing in primary macrophages disrupts HIV-1 Gag and Env colocalization; mutations in Gag or Env that abolish TIP47 interaction impair HIV-1 propagation, infectivity, and Gag-Env coimmunoprecipitation; TIP47 depletion or Gag-TIP47 interaction disruption causes Gag to localize in scattered dots near the plasma membrane. siRNA knockdown, mutagenesis, colocalization imaging, co-immunoprecipitation, infectivity assay Traffic High 20070608
2010 TIP47/PLIN3 overexpression protects NIH3T3 cells from H2O2-induced cell death and prevents mitochondrial depolarization; recombinant TIP47 increases mitochondrial membrane potential and partially prevents Ca2+-induced depolarization in vitro; TIP47 translocates from cytoplasm to mitochondria under oxidative stress. Overexpression, siRNA knockdown, JC1 mitochondrial potential assay, recombinant protein in vitro assay, immunolocalization FEBS letters Medium 20556887
2012 Antisense oligonucleotide (ASO)-mediated reduction of TIP47/PLIN3 in mouse liver decreases hepatic triglyceride content by 35–52%, reduces hepatic steatosis, blunts hepatic triglyceride secretion, improves glucose tolerance, and increases insulin sensitivity in liver, adipose tissue, and muscle. Antisense oligonucleotide treatment in mice, liver histology, triglyceride measurement, glucose/insulin tolerance tests American journal of physiology. Regulatory, integrative and comparative physiology Medium 22378776
2012 Full-length TIP47/PLIN3 adopts an extended conformation in solution with considerable spatial separation of N- and C-termini; the N-terminal region is predominantly β-structure (not helical), contrasting with the helical C-terminal domain, suggesting functional domain separation. Small-angle X-ray scattering (SAXS), solution structure analysis, N-terminal truncation mutants Proteins Medium 22508559
2013 TIP47/PLIN3 interacts with HCV NS5A through its N-terminal PAT domain (NS5A residue W9 critical); TIP47 knockdown causes >10-fold decrease in HCV propagation and HCV RNA replication (shown in subgenomic replicon); TIP47 co-fractionates with NS3, NS5A, NS5B, and viral RNA in low-density LD-rich membrane fractions in HCV-replicating cells. Yeast two-hybrid screen, co-immunoprecipitation, shRNA knockdown, subgenomic replicon assay, point mutagenesis (W9A), membrane flotation assay PLoS pathogens High 23593007
2013 TIP47/PLIN3 binds RNA-loaded NS5A via its N-terminal PAT domain in HCV-replicating cells; overexpression increases released HCV particles while complete knockdown abolishes virus replication; TIP47 stays associated with released HCV particles as shown by co-immunoprecipitation and immunogold electron microscopy. Co-immunoprecipitation, affinity chromatography, yeast two-hybrid, siRNA knockdown, lentiviral overexpression, immunogold electron microscopy Journal of hepatology High 23354285
2013 Rab9 interaction with TIP47/PLIN3 is required for HCV particle release; TIP47 mutants lacking the Rab9 binding domain retain binding to viral particles but misdirect them to the autophagosomal/lysosomal compartment for degradation rather than releasing them; silencing Rab9 abolishes viral replication. Deletion/point mutagenesis of Rab9 binding domain, lentiviral siRNA, co-immunoprecipitation, electron microscopy with immunogold European journal of cell biology Medium 24480419
2013 PLIN3/TIP47 knockdown by siRNA in HL-60-derived neutrophils abolishes lipid droplet formation and reduces PGE2 secretion by 65%; PLIN3 is the only PAT family member expressed in these differentiated neutrophils; PLIN3 suppression also reduces expression of mPGES-1, mPGES-2, and COX-2. siRNA knockdown, immunofluorescence, lipid droplet quantification, ELISA (PGE2), Western blotting PloS one Medium 23936516
2013 TIP47/PLIN3 overexpression or RNAi-mediated depletion in HeLa cells and Jurkat T cells had no significant effect on HIV-1 Env incorporation, virus release, or particle infectivity, contradicting earlier reports of a required role in HIV Env incorporation in these cell types; NMR and SPR confirmed MA binds TIP47. NMR titration, surface plasmon resonance, RNAi, overexpression, infectivity assay Journal of virology Medium 23325685
2019 Plin3/TIP47 interacts with dynein subunit Dync1i1 and mediates colocalization of lipid droplets with microtubules; Plin3 knockdown increases ER triglyceride accumulation and ER dilation after alcohol exposure; Plin3 promotes lipid export from the ER, protecting against ER lipotoxic stress. Co-immunoprecipitation, immunofluorescence colocalization, siRNA knockdown, triglyceride measurement, ER stress markers Journal of cellular biochemistry Medium 31119787
2021 mTORC1 phosphorylates PLIN3 to promote lipid droplet degradation (lipophagy); PLIN3 knockdown abolishes lipophagy induced by oleic acid overload; PLIN3 directly interacts with autophagy proteins FAK200 and ATG16L, suggesting PLIN3 functions as a docking protein for autophagosome formation at lipid droplets. RNA interference knockdown, co-immunoprecipitation, phosphorylation assays, in vitro/in vivo/ex vivo lipophagy assays Hepatology Medium 34233024
2021 ACSS3 reduces lipid droplet deposits by regulating the stability of PLIN3; loss of ACSS3 increases PLIN3 stability, promoting LD accumulation and intratumoral androgen synthesis in prostate cancer cells. Co-immunoprecipitation, Western blotting, Oil Red O staining, LC/MS, siRNA knockdown Theranostics Medium 33391508
2006 TIP47/PLIN3 inhibits retinylester hydrolysis catalyzed by GS2 lipase and hormone-sensitive lipase in keratinocytes; two regions are involved in inhibitory activity: residues within carboxyl α3–α4 helices are essential in the context of the full-length protein, and N-terminal residues contribute in a context-dependent manner. cDNA library screen, deletion mutagenesis, enzyme activity assays The Journal of investigative dermatology Medium 16741517
2007 All-trans-retinol generated by rhodopsin photobleaching triggers rapid translocation of TIP47/PLIN3 from cytosol to lipid droplets in retinal pigment epithelium; this translocation requires both the N-terminal and C-terminal halves of the molecule; a short C-terminal deletion enhances LD localization. Fluorescence microscopy, RNAi, deletion mutagenesis, HPLC retinyl ester measurement Investigative ophthalmology & visual science Medium 17525222

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking. Cell 332 9590177
2002 Functional conservation for lipid storage droplet association among Perilipin, ADRP, and TIP47 (PAT)-related proteins in mammals, Drosophila, and Dictyostelium. The Journal of biological chemistry 325 12077142
2005 S3-12, Adipophilin, and TIP47 package lipid in adipocytes. The Journal of biological chemistry 292 15731108
2000 TIP47 associates with lipid droplets. The Journal of biological chemistry 248 11084026
2009 TIP47 functions in the biogenesis of lipid droplets. The Journal of cell biology 221 19451273
2001 Role of Rab9 GTPase in facilitating receptor recruitment by TIP47. Science (New York, N.Y.) 201 11359012
2004 Structure of a lipid droplet protein; the PAT family member TIP47. Structure (London, England : 1993) 170 15242596
2009 Diacylglycerol enrichment of endoplasmic reticulum or lipid droplets recruits perilipin 3/TIP47 during lipid storage and mobilization. The Journal of biological chemistry 131 19748893
2006 Tail-interacting protein TIP47 is a connector between Gag and Env and is required for Env incorporation into HIV-1 virions. Proceedings of the National Academy of Sciences of the United States of America 114 17003132
2003 Targeting of the human immunodeficiency virus type 1 envelope to the trans-Golgi network through binding to TIP47 is required for env incorporation into virions and infectivity. Journal of virology 106 12768012
2006 Functional compensation for adipose differentiation-related protein (ADFP) by Tip47 in an ADFP null embryonic cell line. The Journal of biological chemistry 100 16968708
2013 Lipid droplet-binding protein TIP47 regulates hepatitis C Virus RNA replication through interaction with the viral NS5A protein. PLoS pathogens 98 23593007
2021 ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3. Theranostics 97 33391508
2006 Immunohistochemical staining for adipophilin, perilipin and TIP47. Journal of clinical pathology 88 16556662
2006 TIP47 is a key effector for Rab9 localization. The Journal of cell biology 83 16769818
2012 Reduction of TIP47 improves hepatic steatosis and glucose homeostasis in mice. American journal of physiology. Regulatory, integrative and comparative physiology 66 22378776
2009 Differential association of adipophilin and TIP47 proteins with cytoplasmic lipid droplets in mouse enterocytes during dietary fat absorption. Biochimica et biophysica acta 62 19698802
2013 TIP47 plays a crucial role in the life cycle of hepatitis C virus. Journal of hepatology 60 23354285
2006 Recruitment of TIP47 to lipid droplets is controlled by the putative hydrophobic cleft. Biochemical and biophysical research communications 54 16808905
2000 Quantitative analysis of TIP47-receptor cytoplasmic domain interactions: implications for endosome-to-trans Golgi network trafficking. The Journal of biological chemistry 49 10829017
2021 A Mammalian Target of Rapamycin-Perilipin 3 (mTORC1-Plin3) Pathway is essential to Activate Lipophagy and Protects Against Hepatosteatosis. Hepatology (Baltimore, Md.) 48 34233024
2009 TIP47, a lipid cargo protein involved in macrophage triglyceride metabolism. Arteriosclerosis, thrombosis, and vascular biology 45 19286631
2013 TIP47 is associated with the hepatitis C virus and its interaction with Rab9 is required for release of viral particles. European journal of cell biology 44 24480419
2001 TIP47 is not a component of lipid droplets. The Journal of biological chemistry 37 11313361
2013 Crucial role of perilipin-3 (TIP47) in formation of lipid droplets and PGE2 production in HL-60-derived neutrophils. PloS one 36 23936516
2004 Spatial integration of TIP47 and adipophilin in macrophage lipid bodies. The Journal of biological chemistry 35 15545278
2010 A Toll-like receptor 9-mediated pathway stimulates perilipin 3 (TIP47) expression and induces lipid accumulation in macrophages. American journal of physiology. Endocrinology and metabolism 33 20628022
2013 Expression of PLIN2 and PLIN3 during oocyte maturation and early embryo development in cattle. Theriogenology 32 24210669
2010 TIP47 is required for the production of infectious HIV-1 particles from primary macrophages. Traffic (Copenhagen, Denmark) 31 20070608
2002 Identification of residues in TIP47 essential for Rab9 binding. Proceedings of the National Academy of Sciences of the United States of America 30 12032303
2013 Reevaluation of the requirement for TIP47 in human immunodeficiency virus type 1 envelope glycoprotein incorporation. Journal of virology 29 23325685
2019 Plin3 protects against alcoholic liver injury by facilitating lipid export from the endoplasmic reticulum. Journal of cellular biochemistry 27 31119787
2010 TIP47 protects mitochondrial membrane integrity and inhibits oxidative-stress-induced cell death. FEBS letters 24 20556887
2001 Overexpression of placental tissue protein 17b/TIP47 in cervical dysplasias and cervical carcinoma. Anticancer research 23 11299819
2020 Feedback activation of GATA1/miR-885-5p/PLIN3 pathway decreases sunitinib sensitivity in clear cell renal cell carcinoma. Cell cycle (Georgetown, Tex.) 22 32783497
2003 Self-assembly is important for TIP47 function in mannose 6-phosphate receptor transport. Traffic (Copenhagen, Denmark) 22 12535272
2021 Suppressed PLIN3 frequently occurs in prostate cancer, promoting docetaxel resistance via intensified autophagy, an event reversed by chloroquine. Medical oncology (Northwood, London, England) 21 34410522
2023 PIWIL1 interacting RNA piR-017724 inhibits proliferation, invasion, and migration, and inhibits the development of HCC by silencing PLIN3. Frontiers in oncology 19 37503320
2014 Higher PLIN5 but not PLIN3 content in isolated skeletal muscle mitochondria following acute in vivo contraction in rat hindlimb. Physiological reports 18 25318747
2009 Preliminary study of TIP47 as a possible new biomarker of cervical dysplasia and invasive carcinoma. Anticancer research 18 19331227
2012 Solution structure studies of monomeric human TIP47/perilipin-3 reveal a highly extended conformation. Proteins 16 22508559
2007 All-trans-retinol generated by rhodopsin photobleaching induces rapid recruitment of TIP47 to lipid droplets in the retinal pigment epithelium. Investigative ophthalmology & visual science 16 17525222
2006 Molecular screening for GS2 lipase regulators: inhibition of keratinocyte retinylester hydrolysis by TIP47. The Journal of investigative dermatology 14 16741517
2010 TIP47 confers resistance to taxol-induced cell death by preventing the nuclear translocation of AIF and Endonuclease G. European journal of cell biology 11 20708296
1999 Is placental tissue protein 17b/TIP47 a new factor in cervical cancer genesis? Anticancer research 10 10697545
2008 Cloning, chromosome mapping and expression pattern of porcine PLIN and M6PRBP1 genes. Genetics, selection, evolution : GSE 8 18298936
2004 In vitro selection and prediction of TIP47 protein-interaction interfaces. Nature methods 8 15782153
2015 Epigenetic harnessing of HCV via modulating the lipid droplet-protein, TIP47, in HCV cell models. FEBS letters 7 26170028
2005 Purification and analysis of TIP47 function in Rab9-dependent mannose 6-phosphate receptor trafficking. Methods in enzymology 7 16473602
2017 The dynamic pattern of PLIN3 in pig oocytes and cumulus cells during in vitro maturation. Zygote (Cambridge, England) 6 29233207
2019 Disorder in milk proteins: adipophilin and TIP47, important constituents of the milk fat globule membrane. Journal of biomolecular structure & dynamics 4 30896308
2004 [The double-play of PP17/TIP47]. Medecine sciences : M/S 4 15525499
2025 Transcription Factor FOSL1 Promotes Cisplatin Resistance in Non-Small Cell Lung Cancer Cells by Modulating the Wnt3a/β-Catenin Signaling through Upregulation of PLIN3 Expression. Frontiers in bioscience (Landmark edition) 3 40152390
2013 The cellular protein TIP47 restricts Respirovirus multiplication leading to decreased virus particle production. Virus research 2 23348195
2026 PLIN3-triggered lipophagic flux releases FFAs to facilitate CSFV propagation. Virulence 0 41656915
2026 PLIN3 overexpression in lung adenocarcinoma promotes M2 macrophage-myofibroblast transition in the tumor microenvironment. Biology direct 0 41943031
2025 Therapeutic Potential of Quercetin, Silibinin, and Crocetin in a High-Fat Diet-Induced Mouse Model of MASLD: The Role of CD36 and PLIN3. Life (Basel, Switzerland) 0 41157197
2025 PLIN3: a multifaceted regulator of lipid droplet dynamics and disease pathogenesis. Medical oncology (Northwood, London, England) 0 41441956
2008 [TIP47: a cellular factor required for envelope glycoproteins incorporation into HIV particles]. Virologie (Montrouge, France) 0 36131457

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