Affinage

PLIN3

Perilipin-3 · UniProt O60664

Length
434 aa
Mass
47.1 kDa
Annotated
2026-04-28
64 papers in source corpus 30 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLIN3 (TIP47) is a PAT-family lipid droplet coat protein that cycles between the cytosol and lipid droplet surfaces in response to diacylglycerol and fatty acid availability, functioning broadly in lipid droplet biogenesis, triglyceride metabolism, lipophagy, and endosomal cargo sorting. Its N-terminal 11-mer helical repeats mediate lipid binding and membrane association — including diacylglycerol-dependent recruitment to the ER and nascent lipid droplets — while the C-terminal four-helix bundle mediates protein–protein interactions including selective binding to mannose 6-phosphate receptor cytoplasmic tails and GTP-bound Rab9, coupling cargo selection to vesicle budding for endosome-to-TGN retrograde transport (PMID:9590177, PMID:11359012, PMID:15242596, PMID:19748893). PLIN3 forms cytosolic homo-oligomers required for transport activity, serves as an mTORC1 phosphorylation substrate that recruits autophagy machinery (FIP200, ATG16L) to lipid droplets for lipophagy, links lipid droplets to dynein-based microtubule transport, and regulates hepatic triglyceride content and insulin sensitivity in vivo (PMID:12535272, PMID:34233024, PMID:31119787, PMID:22378776). PLIN3 also acts as a host factor exploited by HIV-1 — bridging Gag and Env via a ternary complex required for envelope glycoprotein incorporation into virions — and by HCV, where its Rab9-binding domain directs viral particle release (PMID:17003132, PMID:23354285).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Establishing that TIP47 is a selective cargo adaptor in endosome-to-TGN transport answered how mannose 6-phosphate receptors are sorted and recycled from endosomes, founding the field of PLIN3 biology.

    Evidence Yeast two-hybrid, biochemical binding assays, and in vitro transport reconstitution in mammalian cells

    PMID:9590177

    Open questions at the time
    • Structural basis of MPR tail recognition unknown
    • In vivo confirmation in animal models lacking
    • Whether TIP47 acts on other endosomal cargo undetermined
  2. 2000 High

    Discovery that TIP47 associates with lipid droplets upon fatty acid loading revealed a dual-compartment biology, raising the question of whether its endosomal and LD functions are mechanistically separable.

    Evidence Immunofluorescence and subcellular fractionation in HeLa and Leydig cells with oleate loading

    PMID:10829017 PMID:11084026

    Open questions at the time
    • Lipid specificity of LD targeting unknown
    • Relationship between LD and endosomal pools unresolved
  3. 2001 High

    Demonstrating that Rab9-GTP directly binds TIP47 and enhances its MPR affinity established the GTPase-effector coupling mechanism that recruits TIP47 to late endosomes and links cargo recognition to vesicle budding.

    Evidence Recombinant protein binding assays and in vivo transport assays with Rab9 mutants

    PMID:11359012

    Open questions at the time
    • Downstream vesicle coat machinery not identified
    • Whether Rab9 binding competes with LD association unknown
  4. 2002 High

    Mapping the Rab9 binding site (residues 161–169) as distinct from the MPR-binding domain, and showing conserved LD targeting across species, resolved domain modularity and evolutionary conservation of PAT-family LD targeting.

    Evidence Site-directed mutagenesis with CD spectroscopy, GFP-fusion cross-species localization

    PMID:12032303 PMID:12077142

    Open questions at the time
    • Atomic-resolution Rab9–TIP47 interface not solved
    • LD-targeting determinant not precisely mapped
  5. 2003 High

    Discovering that TIP47 forms homo-oligomers (likely hexamers) via its N-terminus and that oligomerization is required for transport but not for MPR binding revealed a functional requirement for higher-order assembly in membrane trafficking, and identifying the gp41 cytoplasmic tail interaction opened the HIV connection.

    Evidence Gel filtration, cross-linking, transport assays with N-terminal fragments; dominant-negative TIP47, mutagenesis of gp41 Y802W803

    PMID:12535272 PMID:12768012

    Open questions at the time
    • Oligomer structure not solved
    • Whether oligomerization is relevant on LDs unknown
    • HIV Env retrograde transport mechanism not fully separated from MPR pathway
  6. 2004 High

    The 2.8 Å crystal structure of the C-terminal domain revealed a novel α/β fold with a four-helix bundle resembling apoE's LDL receptor-binding domain, providing the structural framework for understanding how the C-terminus mediates protein–protein interactions while N-terminal repeats bind lipid.

    Evidence X-ray crystallography

    PMID:15242596

    Open questions at the time
    • Full-length structure unavailable
    • No co-crystal with Rab9 or MPR tail
    • Lipid-binding mode of N-terminal repeats unresolved at atomic level
  7. 2005 High

    Showing that a pre-existing cytosolic TIP47 pool rapidly coats nascent LDs upon oleate addition without new protein synthesis established TIP47 as a sentinel LD coat protein available for immediate triglyceride packaging.

    Evidence Cycloheximide block with oleate loading, subcellular fractionation, and fluorescence microscopy in adipocytes

    PMID:15731108

    Open questions at the time
    • Signal triggering cytosol-to-LD translocation not molecularly defined
    • Post-translational modifications controlling redistribution unknown
  8. 2006 High

    Multiple studies converged to show that TIP47 functionally compensates for ADFP on lipid droplets, regulates triglyceride vs. phospholipid partitioning, inhibits retinylester hydrolases, determines Rab9 compartment identity, and bridges HIV-1 Gag and Env for virion assembly — greatly expanding the functional repertoire beyond endosomal sorting.

    Evidence ADFP-null cells with siRNA double-knockdown and lipid class analysis; Rab chimera localization assays; reciprocal Co-IP of Gag–TIP47–Env with infectivity readouts; lipase inhibition assays with deletion mutants

    PMID:16741517 PMID:16769818 PMID:16808905 PMID:16968708 PMID:17003132

    Open questions at the time
    • Competition/coordination between LD-coating and endosomal roles not resolved
    • Lipase inhibition mechanism not structurally defined
    • Ternary complex stoichiometry unknown
  9. 2009 High

    Identifying diacylglycerol as the ER membrane signal that recruits PLIN3 and demonstrating apolipoprotein-like liposome remodeling activity established the lipid-sensing mechanism and biophysical basis for LD biogenesis, while challenging the physiological relevance of the MPR trafficking role.

    Evidence Membrane-permeable DG treatment, DGAT1 overexpression, lipase inhibitors, in vitro liposome reorganization, siRNA knockdown with LD maturation phenotype

    PMID:19286631 PMID:19451273 PMID:19748893

    Open questions at the time
    • Whether DG sensing and MPR binding can occur simultaneously in the same cell unclear
    • Liposome remodeling activity not confirmed with native ER membranes
    • Direct DG-binding site not mapped
  10. 2010 High

    Confirmation in primary macrophages that TIP47 bridges HIV-1 Gag and Env, and the finding of oxidative stress-dependent mitochondrial translocation with cytoprotective effects, extended functional roles to primary immune cells and mitochondrial biology.

    Evidence siRNA in primary macrophages with infectivity and CoIP; TIP47 overexpression/KD with JC1 mitochondrial assay and recombinant protein in vitro

    PMID:20070608 PMID:20556887

    Open questions at the time
    • Mitochondrial targeting mechanism unknown
    • Whether mitochondrial role is physiological or stress-specific unclear
    • HIV macrophage assembly site architecture not defined
  11. 2012 High

    In vivo antisense knockdown in mice demonstrated that PLIN3 regulates hepatic triglyceride storage, secretion, and systemic glucose/insulin homeostasis, while SAXS revealed that the full-length protein adopts an extended conformation with spatially separated N- and C-terminal domains.

    Evidence Antisense oligonucleotide treatment in HFD-fed mice with metabolic phenotyping; SAXS solution structure of purified full-length protein

    PMID:22378776 PMID:22508559

    Open questions at the time
    • Whether metabolic phenotypes are cell-autonomous or systemic unclear
    • Conformational changes upon lipid or Rab9 binding not characterized
  12. 2013 High

    Discovery that PLIN3 is hijacked by HCV — binding NS5A to support replication and using its Rab9-binding domain for viral particle release — established PLIN3 as a host factor exploited by multiple viruses through distinct mechanisms, and linked LD biology to eicosanoid production in innate immune cells.

    Evidence Yeast two-hybrid, CoIP, NS5A mutagenesis, Rab9-binding-domain mutants, replicon/infectivity assays; siRNA in neutrophils with PGE2 ELISA

    PMID:23354285 PMID:23593007 PMID:23936516 PMID:24480419

    Open questions at the time
    • Whether PLIN3 is incorporated into HCV virions confirmed only by one group
    • Structural basis of NS5A–PLIN3 interaction unknown
    • Eicosanoid link indirect — mechanism connecting LD to COX-2 regulation unclear
  13. 2019 Medium

    Identification of dynein subunit Dync1i1 as a PLIN3 interactor established PLIN3 as a molecular adaptor linking lipid droplets to microtubule-based transport and explained how LD positioning facilitates lipid export from the ER.

    Evidence Co-immunoprecipitation of PLIN3 with Dync1i1, confocal LD–microtubule colocalization, siRNA knockdown with ER stress and TG accumulation readouts

    PMID:31119787

    Open questions at the time
    • Direct binding vs. indirect complex not distinguished
    • Dynein interaction domain on PLIN3 not mapped
    • In vivo relevance of LD transport function not tested
  14. 2021 Medium

    Discovering that mTORC1 phosphorylates PLIN3 to promote lipophagy via recruitment of FIP200 and ATG16L established PLIN3 as a signal-responsive docking platform for autophagosome nucleation on lipid droplets, while ACSS3-dependent regulation of PLIN3 stability linked LD metabolism to androgen synthesis in prostate cancer.

    Evidence CoIP of PLIN3 with FIP200/ATG16L, mTORC1 kinase assays, lipophagy quantification in hepatocytes and human liver slices; ACSS3 CoIP, xenograft model with lipid analysis

    PMID:33391508 PMID:34233024

    Open questions at the time
    • Specific mTORC1 phosphorylation sites on PLIN3 not fully mapped
    • Whether lipophagy role depends on oligomerization unknown
    • ACSS3-mediated degradation pathway (proteasomal vs. lysosomal) not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of full-length PLIN3 in complex with Rab9 and lipid membranes, the molecular basis for how PLIN3 partitions between endosomal, LD, ER, and mitochondrial compartments, and whether its MPR trafficking and LD biogenesis roles operate in the same cell type simultaneously.
  • No full-length co-crystal or cryo-EM structure with any partner
  • Post-translational modification landscape (beyond mTORC1) uncharacterized
  • In vivo phenotype of complete PLIN3 knockout in mice not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 5 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005811 lipid droplet 7 GO:0005768 endosome 3 GO:0005829 cytosol 3 GO:0005739 mitochondrion 1 GO:0005783 endoplasmic reticulum 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-1643685 Disease 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9612973 Autophagy 1
Partners
ATG16L1DYNC1I1FIP200IGF2RM6PRPLIN2RAB9A
Complex memberships
Gag–TIP47–Env ternary complexRab9–TIP47 effector complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 TIP47 (PLIN3) binds selectively to the cytoplasmic domains of cation-independent and cation-dependent mannose 6-phosphate receptors (MPRs) and is required for MPR transport from endosomes to the trans-Golgi network; it recognizes a phenylalanine/tryptophan signal in the cytoplasmic tail of the cation-dependent MPR essential for endosomal sorting. Biochemical binding assays, in vitro transport assay, in vivo functional rescue, yeast two-hybrid identification Cell High 9590177
2001 TIP47 (PLIN3) binds directly to the active, GTP-bound form of Rab9 GTPase; Rab9 increases the affinity of TIP47 for MPR cytoplasmic domains, and a functional Rab9 binding site in TIP47 is required for stimulation of MPR transport in vivo, indicating that Rab9 recruits TIP47 onto late endosomes to couple cargo selection to vesicle budding. Direct binding assay (recombinant proteins), affinity chromatography, in vivo transport assay with Rab9 mutants Science High 11359012
2000 TIP47 (PLIN3) associates with nascent lipid droplets in HeLa and MA10 Leydig cells; upon fatty acid loading, a significant portion of cytosolic TIP47 redistributes to the lipid droplet fraction, demonstrating it is a lipid droplet-associated protein. Immunofluorescence microscopy, subcellular fractionation, fatty acid loading experiments The Journal of biological chemistry High 11084026
2000 TIP47 binds more tightly to the cation-independent MPR (Kd ~1 µM) than to the cation-dependent MPR (Kd ~3 µM) and does not interact with the cytoplasmic domains of furin, TGN38, or metallocarboxypeptidase D, indicating highly selective cargo recognition within the endosome-to-TGN pathway. Quantitative in vitro binding assay with recombinant proteins, surface plasmon resonance or equivalent The Journal of biological chemistry High 10829017
2002 TIP47 (PLIN3) residues 161–169 are essential but not sufficient for Rab9 binding; mutation of these residues decreases Rab9 binding without altering global fold or MPR cytoplasmic domain binding capacity, revealing distinct binding domains for Rab9 and MPR within TIP47. Site-directed mutagenesis, circular dichroism, partial proteolysis, binding assays with recombinant proteins 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 in mammalian cells, and PAT-family proteins from Drosophila and Dictyostelium can also target lipid droplet surfaces in heterologous systems, demonstrating evolutionarily conserved sequence/structural elements sufficient for lipid droplet targeting. GFP fusion localization, co-fractionation with isolated lipid droplets, immunofluorescence with specific antibodies, heterologous expression The Journal of biological chemistry High 12077142
2003 TIP47 (PLIN3) forms homo-oligomers (likely hexamers) in the cytosol via an N-terminal oligomerization domain (residues 1–151); oligomerization is not required for MPR cytoplasmic domain binding but is required for stimulation of MPR transport from endosomes to the trans-Golgi in vivo. Gel filtration chromatography, chemical cross-linking, co-expression of N-terminal fragments with full-length TIP47, in vivo transport assay Traffic High 12535272
2004 Crystal structure of the C-terminal domain of TIP47 (PLIN3) resolved at 2.8 Å reveals an α/β domain of novel topology and a four-helix bundle resembling the LDL receptor-binding domain of apolipoprotein E, suggesting the C-terminal region is involved in protein–protein interactions while N-terminal 11-mer helical repeats interact with lipid. X-ray crystallography at 2.8 Å resolution Structure High 15242596
2005 S3-12 (PLIN4), TIP47 (PLIN3), and adipophilin together coat nascent lipid droplets that emerge upon oleate addition in adipocytes; TIP47 redistributes from cytosolic fractions to lipid droplet fractions in an oleate-dependent manner without requiring new protein synthesis, indicating a pre-existing cytosolic pool of TIP47 serves as a ready reservoir for rapid packaging of newly synthesized triacylglycerol. Fluorescence microscopy, subcellular fractionation, cycloheximide inhibition, oleate loading The Journal of biological chemistry High 15731108
2006 The C-terminal half of TIP47 (PLIN3), specifically the putative hydrophobic cleft, mediates lipid droplet targeting and responsiveness to fatty acids; ADRP overexpression or downregulation reciprocally regulates TIP47 occupancy on lipid droplets, and Rab18 overexpression decreases ADRP but not TIP47 from droplets, indicating distinct LD-targeting mechanisms for TIP47 vs. ADRP. Deletion mutant analysis, immunofluorescence, Rab18 overexpression, ADRP siRNA knockdown Biochemical and biophysical research communications Medium 16808905
2006 TIP47 (PLIN3) binds the MA (matrix) domain of HIV-1 Gag, interacts with HIV-1 Env (gp41 cytoplasmic tail), and forms a Gag–TIP47–Env ternary complex; TIP47 silencing impairs Env incorporation into virions and infectivity, and overexpression increases Env packaging, establishing TIP47 as a cellular connector required for HIV-1 Env incorporation. Co-immunoprecipitation, siRNA knockdown, mutagenesis of Gag and Env interaction sites, infectivity assays, co-localization microscopy Proceedings of the National Academy of Sciences of the United States of America High 17003132
2003 HIV-1 Env glycoprotein localizes mainly to the trans-Golgi network (TGN) via determinants in the gp41 cytoplasmic tail; the gp41 cytoplasmic domain binds TIP47 (PLIN3), and this interaction (requiring a Y802W803 diaromatic motif) is required for retrograde Env transport from endosomes to the TGN, Env incorporation into virions, and viral infectivity. Internalization assays, dominant-negative TIP47 mutant overexpression, site-directed mutagenesis of gp41, co-immunoprecipitation, viral infectivity assay Journal of virology High 12768012
2006 TIP47 (PLIN3) is a key effector for Rab9 localization; changing cellular concentrations of TIP47 shifts Rab5/9 or Rab1/9 chimeras toward Rab9 compartments, demonstrating that effector proteins and Rab GTPases mutually depend on each other for correct steady-state localization. Rab chimera generation, quantitative Rab effector binding assays, altered TIP47 expression with localization readout The Journal of cell biology High 16769818
2006 In ADFP-null cells, TIP47 (PLIN3) is the sole PAT-family protein on lipid droplets and functionally compensates for ADFP loss; siRNA-mediated TIP47 knockdown in ADFP-null cells reduces lipid droplet formation and shifts exogenous fatty acid utilization from triglycerides to phospholipids, demonstrating TIP47's role in regulating triglyceride metabolism. ADFP-null cell lines, mass spectrometry identification, immunoblotting, immunocytochemistry, siRNA knockdown, lipid class analysis The Journal of biological chemistry High 16968708
2009 TIP47 (PLIN3) is recruited to lipid droplets by an N-terminal sequence comprising 11-mer repeats; it has apolipoprotein-like properties and reorganizes liposomes into small lipid discs in vitro. Knockdown of TIP47 blocks lipid droplet maturation and decreases incorporation of triacylglycerol into LDs; TIP47 does not co-localize with organelles of the biosynthetic or endocytic pathway, arguing against a role in MPR trafficking. siRNA knockdown of TIP47, lipid droplet morphology analysis, in vitro liposome reorganization assay, N-terminal deletion mutants for LD targeting, MPR trafficking assays The Journal of cell biology High 19451273
2009 Diacylglycerol (DG) enrichment of the endoplasmic reticulum recruits perilipin 3 (TIP47) to ER membranes and to lipid droplets emerging from the ER; membrane-permeable DG drives PLIN3 to the ER, stabilization of DG (via lipase or acyltransferase inhibitors) enhances ER recruitment, and DGAT1 expression (which converts DG to TAG) attenuates DG-induced ER recruitment, linking PLIN3 recruitment to cellular acylglycerol metabolic state. AlF4- membrane trafficking block, DG lipase inhibitor (RHC80267), membrane-permeable DG treatment, DGAT1 overexpression, subcellular fractionation, immunofluorescence The Journal of biological chemistry High 19748893
2009 TIP47 (PLIN3) is present in the plasma membrane of macrophages and clusters there upon oleate treatment; TIP47 protein levels directly correlate with triglyceride content in macrophages—overexpression of EGFP-TIP47 increases triglycerides while siRNA depletion decreases them, and TIP47 siRNA knockdown following ADFP depletion causes migration of TIP47 from cytoplasm to lipid droplets. Freeze-fracture cytochemistry, siRNA knockdown, EGFP-TIP47 overexpression, triglyceride quantification Arteriosclerosis, thrombosis, and vascular biology Medium 19286631
2012 Antisense oligonucleotide-mediated reduction of TIP47 (PLIN3) in mouse liver decreases hepatic triglyceride content (by 35–52%), reduces steatosis, blunts hepatic triglyceride secretion, improves glucose tolerance, and increases insulin sensitivity, establishing TIP47 as a regulator of hepatic lipid and glucose metabolism in vivo. Antisense oligonucleotide (ASO) treatment in high-fat diet-fed mice, liver triglyceride quantification, glucose tolerance test, insulin tolerance test, liver histology American journal of physiology. Regulatory, integrative and comparative physiology High 22378776
2013 TIP47 (PLIN3) interacts with HCV NS5A via the N-terminus of NS5A (α-helical membrane-tethering domain); shRNA knockdown of TIP47 causes >10-fold decrease in HCV propagation and a similar reduction in subgenomic replicon replication; a single NS5A point mutation (W9A) disrupting TIP47 interaction severely decreases HCV RNA replication; TIP47 co-fractionates with NS3, NS5A, NS5B, and viral RNA in LD-rich membrane fractions in replicating cells. Yeast two-hybrid, co-immunoprecipitation in Huh7 cells, shRNA knockdown, subgenomic replicon assay, NS5A site-directed mutagenesis, membrane flotation assay PLoS pathogens High 23593007
2013 TIP47 (PLIN3) binds RNA-loaded NS5A via the N-terminal PAT domain; overexpression of TIP47 increases released HCV virions while silencing abolishes virus replication; TIP47 associates with viral particles and is found on released HCV particles; destruction of the Rab9-binding domain of TIP47 (without affecting NS5A binding or genome replication) prevents HCV particle release and misdirects viral particles to autophagosomal/lysosomal compartments for degradation, establishing that Rab9-complexed TIP47 is required for proper HCV particle release. Co-immunoprecipitation, affinity chromatography, yeast two-hybrid, siRNA/lentiviral knockdown, immunogold electron microscopy, TIP47 deletion/mutation constructs Journal of hepatology / European journal of cell biology High 23354285 24480419
2013 PLIN3 (TIP47) siRNA knockdown in HL-60-derived neutrophils essentially eliminates lipid droplet formation induced by P. gingivalis LPS and reduces PGE2 secretion by 65%, also suppressing COX-2 and microsomal PGE synthase-1 and -2, linking PLIN3 to lipid droplet biogenesis and the inflammatory eicosanoid production pathway. siRNA knockdown, LPS stimulation, Oil Red O / BODIPY lipid droplet staining, PGE2 ELISA, Western blotting for prostaglandin synthetic enzymes PloS one Medium 23936516
2007 All-trans-retinol generated by rhodopsin photobleaching induces rapid translocation of TIP47 (PLIN3) from the cytosol to lipid droplets in retinal pigment epithelium cells; this requires both the N-terminal and C-terminal halves of TIP47, as deletion of either abolishes LD localization; RNAi-mediated TIP47 knockdown does not significantly affect retinyl ester storage amounts. Light stimulation of dark-adapted mouse eyes, all-trans-retinol treatment of ARPE-19 cells, immunofluorescence quantification, deletion mutant analysis, RNAi knockdown, HPLC retinyl ester quantification Investigative ophthalmology & visual science Medium 17525222
2006 TIP47 (PLIN3) inhibits retinylester hydrolysis by GS2 lipase and hormone-sensitive lipase in keratinocytes; deletion mutant analysis shows two contributing regions: residues within the C-terminal α3–α4 helices are essential in the context of full-length protein, and N-terminal residues also contribute, establishing TIP47 as a regulator of lipase activity. cDNA expression library screen, enzyme inhibition assay, deletion mutant analysis The Journal of investigative dermatology Medium 16741517
2010 TIP47 (PLIN3) overexpression protects NIH3T3 cells from oxidative stress-induced cell death and prevents hydrogen-peroxide-induced mitochondrial depolarization; recombinant TIP47 increases mitochondrial membrane potential and partially prevents Ca2+-induced depolarization in vitro; suppression of TIP47 in HeLa cells facilitates oxidative-stress-induced cell death; TIP47 translocates to mitochondria under oxidative stress conditions. TIP47 overexpression and siRNA suppression, JC1 mitochondrial potential assay, recombinant protein in vitro mitochondrial assay, cell death assays FEBS letters Medium 20556887
2010 TIP47 (PLIN3) is required for the production of infectious HIV-1 from primary macrophages; TIP47 silencing disrupts Gag–Env colocalization; mutations in Gag or Env that abolish TIP47 interaction impair infectivity and prevent Gag–Env coimmunoprecipitation; disruption of Gag–TIP47 interaction causes Gag to localize in scattered dots near the plasma membrane. siRNA knockdown in primary macrophages, co-immunoprecipitation, site-directed mutagenesis of Gag/Env TIP47-interaction sites, confocal co-localization, infectivity assays Traffic High 20070608
2021 mTORC1 phosphorylates PLIN3 to promote lipid droplet degradation (lipophagy) in hepatocytes; PLIN3 knockdown abolishes lipophagy; PLIN3 directly interacts with autophagy proteins FAK200 (FIP200) and ATG16L, suggesting PLIN3 functions as a docking protein for autophagosome formation on lipid droplets. RNA interference knockdown, co-immunoprecipitation of PLIN3 with FIP200 and ATG16L, mTORC1 phosphorylation assay, lipophagy quantification in fibroblasts and primary hepatocytes, in vivo mouse model and ex vivo human liver slices Hepatology Medium 34233024
2019 PLIN3 interacts with dynein subunit Dync1i1 and mediates colocalization of lipid droplets with microtubules; PLIN3 knockdown increases sensitivity to alcohol-induced apoptosis, ER stress, and inflammatory cytokine release, and causes TG accumulation in the ER with ER dilation, establishing PLIN3 as an adapter mediating LD transport along microtubules and facilitating lipid export from the ER. Co-immunoprecipitation of PLIN3 with Dync1i1, confocal imaging of LD-microtubule colocalization, siRNA knockdown, ER stress markers, cell death assays, triglyceride quantification in ER fractions Journal of cellular biochemistry Medium 31119787
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 (contrasting with the largely helical C-terminus), suggesting functional domain separation consistent with distinct lipid-binding and protein–protein interaction roles. Small-angle X-ray scattering (solution structure), N-terminal truncation mutants, purification strategy for monodisperse full-length protein Proteins Medium 22508559
2021 ACSS3 reduces lipid droplet deposits by regulating the stability of the LD coat protein PLIN3; loss of ACSS3 increases PLIN3 stability, promoting LD accumulation, intratumoral androgen synthesis, and CRPC progression. Co-immunoprecipitation, Western blotting, Oil Red O assay, LC/MS lipid analysis, xenograft model Theranostics Medium 33391508

Source papers

Stage 0 corpus · 64 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 291 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 130 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 82 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
1986 Identification and characterization of the nonphosphorylated precursor of pp17, a phosphoprotein associated with phorbol ester induction of growth arrest and monocytic differentiation in HL-60 promyelocytic leukemia cells. The Journal of biological chemistry 61 3464595
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.) 45 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
1998 Cloning and sequence analysis of cDNAs encoding human placental tissue protein 17 (PP17) variants. European journal of biochemistry 37 9874244
2013 Crucial role of perilipin-3 (TIP47) in formation of lipid droplets and PGE2 production in HL-60-derived neutrophils. PloS one 35 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
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
2020 Feedback activation of GATA1/miR-885-5p/PLIN3 pathway decreases sunitinib sensitivity in clear cell renal cell carcinoma. Cell cycle (Georgetown, Tex.) 21 32783497
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
2023 PIWIL1 interacting RNA piR-017724 inhibits proliferation, invasion, and migration, and inhibits the development of HCC by silencing PLIN3. Frontiers in oncology 17 37503320
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 Cloning and sequencing of human oncodevelopmental soluble placental tissue protein 17 (PP17): homology with adipophilin and the mouse adipose differentiation-related protein. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 10393528
1999 Is placental tissue protein 17b/TIP47 a new factor in cervical cancer genesis? Anticancer research 10 10697545
2019 Utilization of oil palm decanter cake for valuable laccase and manganese peroxidase enzyme production from a novel white-rot fungus, Pseudolagarobasidium sp. PP17-33. 3 Biotech 8 31696022
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
1993 The development of an enzyme immunoassay for placental tissue protein 17 (PP17) and its clinical significance. Asia-Oceania journal of obstetrics and gynaecology 1 8250767
2026 PLIN3-triggered lipophagic flux releases FFAs to facilitate CSFV propagation. Virulence 0 41656915
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
2024 Phosphatidylcholine and ceramide derivatives from white rot fungus Microporus xanthropus PP17-20. Journal of Asian natural products research 0 38940405
2008 [TIP47: a cellular factor required for envelope glycoproteins incorporation into HIV particles]. Virologie (Montrouge, France) 0 36131457