Affinage

LAMP3

Lysosome-associated membrane glycoprotein 3 · UniProt Q9UQV4

Length
416 aa
Mass
44.3 kDa
Annotated
2026-06-10
76 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LAMP3 (DC-LAMP/CD63) is a lysosome-associated membrane glycoprotein of late endosomes and lamellar bodies that functions at the intersection of endolysosomal trafficking, surfactant homeostasis, and stress-adaptive signaling (PMID:9768752, PMID:14982840, PMID:34161347). Its transcription is directly induced by ATF4 downstream of the PERK/eIF2α arm of the unfolded protein response, activated by hypoxia, ER stress, and proteasomal inhibition independently of HIF-1α, with ATF4 binding the LAMP3 promoter; c-Myc and KDM6A-mediated H3K27me3 demethylation provide additional transcriptional inputs (PMID:19726095, PMID:32312748, PMID:40450055, PMID:39180205). In the lung, LAMP3 localizes to lamellar bodies of alveolar type II pneumocytes where it is required for lamellar body biogenesis and pulmonary surfactant homeostasis, interacting directly with surfactant proteins SP-B and SP-C; loss-of-function variants cause lamellar body maturation arrest and are linked to childhood interstitial lung disease (PMID:14982840, PMID:34161347, PMID:32150563, PMID:40023045). Through its endolysosomal residence LAMP3 cycles between endocytic and secretory compartments, governs degradation of membrane cargo such as NKCC1 and AQP5, modulates autophagic flux, and can trigger lysosomal membrane permeabilization with cathepsin release and caspase activation (PMID:10793155, PMID:34802379, PMID:36329045, PMID:24434718). As a downstream effector of the PERK/ATF4 axis, LAMP3 promotes hypoxia-induced tumor cell migration, invasion, metastasis, and radioresistance, acting via PI3K/Akt, FAK/paxillin/ERK (through interaction with RPL21), and suppression of PKA-VASP(Ser239) phosphorylation (PMID:16204031, PMID:23294542, PMID:24045183, PMID:32200035, PMID:37062845). LAMP3 also facilitates intracellular Salmonella proliferation and HSV-2 and KSHV replication by routing pathogens through the endolysosomal pathway (PMID:27329040, PMID:36350153, PMID:36377873).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1998 Medium

    Established LAMP3 as a lysosomal membrane glycoprotein dynamically associated with the antigen-presentation machinery, framing it as an endolysosomal trafficking component rather than a static lysosomal marker.

    Evidence Confocal microscopy with MAb detection in in vitro-differentiated dendritic cells

    PMID:9768752

    Open questions at the time
    • No molecular function for LAMP3 in MHC II loading defined
    • Whether localization reflects a causal role in presentation untested
  2. 2000 Medium

    Showed that LAMP3 cycles between multivesicular late endosomes and secretory organelles, with late-endosome transit required for recycling, defining its compartmental itinerary.

    Evidence Subcellular fractionation, immunofluorescence and U18666A pharmacological perturbation in primary endothelial cells

    PMID:10793155

    Open questions at the time
    • Trafficking determinants/sorting signals not mapped
    • Functional consequence of recycling not established
  3. 2004 High

    Identified lamellar bodies of type II pneumocytes as a major LAMP3 compartment, linking the protein to surfactant-storage organelles.

    Evidence Immunoelectron microscopy and immunohistochemistry across mouse, sheep, and human lung

    PMID:14982840

    Open questions at the time
    • Co-localization did not establish a functional requirement
    • Interaction with surfactant components not tested at this stage
  4. 2005 High

    Demonstrated a direct pro-metastatic function for LAMP3, moving it from descriptive marker to causal driver of cancer cell behavior.

    Evidence Gain-of-function overexpression with in vitro invasion and in vivo xenograft metastasis assays in cervical cancer cells

    PMID:16204031

    Open questions at the time
    • Downstream signaling mechanism unknown
    • Endogenous loss-of-function not yet tested
  5. 2009 High

    Placed LAMP3 downstream of the PERK/eIF2α/ATF4 UPR arm as a hypoxia-inducible gene independent of HIF-1α, defining its principal regulatory pathway.

    Evidence Microarray, qPCR and RNAi/shRNA knockdown of PERK and ATF4 with ER-stress agents in multiple cell lines

    PMID:19726095

    Open questions at the time
    • Direct promoter binding not shown until later
    • Functional output of induction not yet connected
  6. 2013 High

    Connected the PERK/ATF4/LAMP3 axis to functional outputs by showing LAMP3 mediates hypoxia-induced migration/invasion and radioresistance via the DNA damage response.

    Evidence Sequential siRNA knockdown of PERK/ATF4/LAMP3 with migration, invasion, clonogenic and γ-H2AX assays in breast cancer cells

    PMID:23294542 PMID:23891100

    Open questions at the time
    • How a lysosomal protein influences DNA damage repair unresolved
    • Effector signaling between LAMP3 and migration machinery undefined
  7. 2013 High

    Validated LAMP3 as an in vivo mediator of hypoxia-driven metastasis and a tumor-amplified gene, strengthening its clinical relevance.

    Evidence Inducible shRNA orthotopic cervical cancer xenografts with FISH copy-number analysis of human tumors

    PMID:24045183

    Open questions at the time
    • Molecular mechanism of migration promotion still not defined
    • Causality of copy-number amplification not functionally tested
  8. 2015 Medium

    Generalized ATF4-driven LAMP3 induction to proteasomal stress and assigned a pro-survival, autophagy-enhancing role.

    Evidence siRNA knockdown and proteasome inhibition with autophagic-flux and apoptosis assays in neuroblastoma cells

    PMID:25681212

    Open questions at the time
    • Mechanism by which LAMP3 enhances autophagic flux unknown
    • Context-dependence versus cancer cell phenotypes unclear
  9. 2014 Medium

    Linked LAMP3-modulated autophagy to therapy resistance, showing LAMP3 sustains autophagic flux to confer tamoxifen resistance.

    Evidence siRNA knockdown with LC3B/p62 readouts and tamoxifen-resistant breast cancer cell cultures

    PMID:24434718

    Open questions at the time
    • Direct molecular role of LAMP3 in autophagosome-lysosome fusion not shown
    • Apparently opposing effects on flux across studies unreconciled
  10. 2016 Medium

    Defined PI3K/Akt as a LAMP3-engaged signaling output, here driving lipogenic enzyme expression and lipid accumulation in hepatocytes.

    Evidence Overexpression with PI3K/Akt inhibitor rescue and lipid/triglyceride readouts in HCC cells

    PMID:29056532

    Open questions at the time
    • How LAMP3 activates Akt mechanistically unknown
    • Physiological relevance beyond overexpression untested
  11. 2016 Medium

    Identified LAMP3 as a host factor recruited to pathogen vacuoles that supports intracellular bacterial proliferation.

    Evidence siRNA knockdown, super-resolution imaging of Salmonella-containing vacuoles and bacterial recovery in THP-1 macrophages

    PMID:27329040

    Open questions at the time
    • Mechanism of recruitment to vacuoles unknown
    • Whether LAMP3 directly aids bacterial survival or alters vacuole maturation unclear
  12. 2020 High

    Established ATF4 as a direct transcriptional activator of LAMP3, closing the regulatory loop opened in 2009.

    Evidence ChIP, dual-luciferase reporter with binding-site mutation, knockdown and overexpression

    PMID:32312748

    Open questions at the time
    • Additional co-regulators at the promoter not mapped
    • Cell-type specificity of ATF4 control not addressed
  13. 2020 Medium

    Revealed roles for LAMP3 in autoantigen release via extracellular vesicles and in PKA-VASP(Ser239)-controlled cell motility, extending its function to secretion and a defined motility axis.

    Evidence Overexpression with EV isolation/apoptosis assays in salivary epithelial cells; sequential LAMP3/PKA-subunit knockdown with phospho-VASP and migration assays in ESCC

    PMID:32200035 PMID:32939030

    Open questions at the time
    • How LAMP3 represses PKA-VASP phosphorylation mechanistically unknown
    • Connection between EV release and endolysosomal cycling undefined
  14. 2021 High

    Provided genetic proof that LAMP3 regulates pulmonary surfactant homeostasis and showed it can drive lysosomal membrane permeabilization and caspase-dependent death.

    Evidence CRISPR/Cas9 knockout mice with surfactant/lipid/lung-function analysis; stable overexpression with galectin-3 LMP, cathepsin-release and caspase assays

    PMID:34161347 PMID:34802379

    Open questions at the time
    • Molecular mechanism linking LAMP3 levels to membrane integrity unknown
    • How LAMP3 controls surfactant lipid composition not defined
  15. 2020 Medium

    Showed a LAMP-domain missense variant arrests lamellar body maturation, establishing LAMP3 as required for organelle biogenesis.

    Evidence GWAS plus exome sequencing in affected dogs with transmission electron microscopy of lung tissue

    PMID:32150563

    Open questions at the time
    • Mechanism by which the LAMP domain supports lamellar body assembly unknown
    • Variant studied in a single natural model
  16. 2022 Medium

    Demonstrated LAMP3 promotes endolysosomal degradation of secretory membrane proteins (NKCC1, AQP5) and enhances viral entry, generalizing its role as a regulator of endolysosomal cargo flux.

    Evidence Overexpression mouse model with protein quantification, salivary flow and AAV2 internalization assays

    PMID:36329045

    Open questions at the time
    • How LAMP3 accelerates cargo degradation mechanistically unknown
    • Whether degradation is direct or indirect via altered trafficking unresolved
  17. 2022 Medium

    Established LAMP3 as a proviral host factor for HSV-2 and KSHV acting through the endolysosomal pathway and ATF4-coupled Akt/ERK activation.

    Evidence Isogenic OE/KO cell lines with virion quantification, co-localization imaging and endosomal inhibitors (HSV-2); siRNA/OE with Akt/ERK and viral readouts (KSHV)

    PMID:36350153 PMID:36377873

    Open questions at the time
    • Direct viral-LAMP3 molecular contacts not defined
    • Whether LAMP3 acts on entry, trafficking, or replication step-specifically unclear
  18. 2023 Medium

    Identified RPL21 as a direct LAMP3 partner and the FAK/paxillin/ERK pathway as an effector route, providing a mechanistic basis for LAMP3-driven invasion.

    Evidence GST/His pull-down domain mapping, Co-IP, ubiquitin-proteasome and focal-adhesion assays with orthotopic CRC metastasis model

    PMID:37062845

    Open questions at the time
    • How an endolysosomal protein engages cytosolic RPL21 spatially unresolved
    • Reciprocal validation of focal-adhesion control limited to one model
  19. 2023 Medium

    Showed extracellular LAMP3 itself acts as a cell-to-cell apoptotic signal, demonstrating a non-cell-autonomous function.

    Evidence Extracellular-particle isolation, proteomics, recombinant LAMP3 internalization and caspase-inhibitor experiments

    PMID:36788255

    Open questions at the time
    • Receptor/uptake mechanism for extracellular LAMP3 unknown
    • Physiological versus overexpression-driven relevance untested
  20. 2025 Medium

    Provided human disease causation, linking bi-allelic LAMP3 variants to childhood interstitial lung disease and demonstrating direct LAMP3 interaction with SP-B and SP-C.

    Evidence Exome sequencing, NMD/glycosylation analysis of mutants and co-immunoprecipitation of LAMP3 with SP-B/SP-C

    PMID:40023045

    Open questions at the time
    • Structural basis of LAMP3-surfactant protein binding undefined
    • How interaction supports lamellar body function mechanistically unresolved
  21. 2025 Medium

    Extended LAMP3's regulatory inputs to c-Myc and its outputs to glucose metabolism reprogramming and NF-κB-coupled autophagy suppression in ischemia.

    Evidence Dual-luciferase c-Myc binding assay with knockdown in TSCC; OGD/R and MCAO/R models with NF-κB inhibitor rescue

    PMID:39954716 PMID:40450055

    Open questions at the time
    • Mechanism connecting LAMP3 to NF-κB activation undefined
    • Direct role in metabolic reprogramming versus secondary effect unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The unifying molecular activity of LAMP3 — how a single endolysosomal/lamellar-body glycoprotein mechanistically links surfactant organelle biogenesis, autophagy/LMP control, multiple oncogenic signaling cascades, and pathogen trafficking — remains undefined.
  • No biochemical activity or structural mechanism explaining diverse phenotypes
  • No reconciliation of pro- versus anti-autophagic effects across contexts
  • Direct membrane/cargo-binding determinants of LAMP3 not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 2
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005576 extracellular region 2 GO:0005764 lysosome 2 GO:0005768 endosome 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-9612973 Autophagy 3 R-HSA-168256 Immune System 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
RPL21SFTPBSFTPCUSP4

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 DC-LAMP (LAMP3) is a lysosome-associated membrane glycoprotein that is transiently present in the MHC class II compartment immediately before translocation of MHC class II molecules to the dendritic cell surface, after which it concentrates in perinuclear lysosomes, suggesting a role in lysosome function during antigen presentation. Confocal microscopy, MAb detection, in vitro DC differentiation with LPS/TNFα/CD40L activation Immunity Medium 9768752
2000 CD63/LAMP3 in human endothelial cells distributes predominantly to internal membranes of multivesicular late endosomes and cycles between endocytic compartments and Weibel-Palade bodies (secretory organelles); treatment with U18666A (mimicking Niemann-Pick type C) causes accumulation in late endosomes and failure to reach Weibel-Palade bodies, indicating that late endosome transit is required for recycling. Subcellular fractionation, immunofluorescence, pharmacological inhibition (U18666A), live-cell trafficking assays in primary endothelial cells Molecular biology of the cell Medium 10793155
2004 DC-LAMP (LAMP3) is constitutively expressed in type II pneumocytes and co-localizes with lbm180 (a marker of lamellar body limiting membrane containing surfactant protein B) and intracellular MHC class II molecules in the same organelles; expression is occasionally detected at the cell surface of type II pneumocytes. Confocal microscopy, immunoelectron microscopy, immunohistochemistry in mouse/sheep/human lung tissue The American journal of pathology High 14982840
2005 Overexpression of LAMP3 in human uterine cervical cancer cells (TCS line) significantly increases in vitro cell migration and in vivo distant metastasis (9/11 vs 1/11 mice), with histological evidence of lymph-vascular space invasion, establishing a direct pro-metastatic function. LAMP3 expression vector transfection, in vitro invasion assay, in vivo metastasis assay (xenograft), histology Cancer research High 16204031
2009 LAMP3 is strongly induced by hypoxia at both mRNA and protein levels through activation of the PERK/eIF2α/ATF4 arm of the unfolded protein response (UPR), independently of HIF-1α; this was established by transient RNAi and stable shRNA knockdown of PERK and ATF4. Microarray, qPCR, Western blot, siRNA/shRNA knockdown, immunohistochemistry, ER stress agent treatment Radiotherapy and oncology High 19726095
2010 The lumenal domain of DC-LAMP is not required for MHC class I and II antigen presentation; fusion constructs lacking the lumenal domain of DC-LAMP linked to HIV antigens induced equivalent antigen-specific CD4+ and CD8+ T cell responses as full-length DC-LAMP fusion constructs, but the DC-LAMP targeting sequence itself is absolutely required for optimal T cell stimulation. mRNA electroporation of DCs, antigen-specific T cell response assays (with/without lumenal domain constructs) Human gene therapy Medium 19903083
2013 LAMP3 knockdown via siRNA reduces hypoxia-induced migration and invasion of MDA-MB-231 breast cancer cells, placing LAMP3 downstream of PERK and ATF4 in the UPR pathway that mediates hypoxia-stimulated cell migration. siRNA knockdown of PERK, ATF4, LAMP3; transwell migration assay, gap closure assay, 3D collagen invasion assay Breast cancer research High 23294542
2013 LAMP3 knockdown radiosensitizes breast cancer cells and attenuates the DNA damage response after irradiation, as shown by reduced γ-H2AX foci and diminished activation of DNA damage repair proteins, placing LAMP3 as a mediator of radioresistance via the PERK/ATF4/LAMP3-arm of the UPR. siRNA knockdown, clonogenic survival assay, Western blot for DNA damage repair proteins, immunocytochemistry for γ-H2AX foci Radiotherapy and oncology Medium 23891100
2013 Induced disruption of PERK signaling in established orthotopic cervical cancer xenografts completely inhibits hypoxia-induced lymph node metastasis, and LAMP3 is identified as a key mediator of this effect via its ability to promote cell migration; LAMP3 gene amplification in human cervical tumors is augmented by both copy number alterations and hypoxia. Inducible shRNA cell lines, orthotopic xenograft model of cervical cancer, FISH for gene copy number, immunofluorescence Clinical cancer research High 24045183
2014 LAMP3 knockdown in MCF7 breast cancer cells increases tamoxifen sensitivity and elevates LC3B and p62 autophagy markers, indicating suppressed autophagic flux completion; tamoxifen-resistant MCF7 cells show sevenfold higher LAMP3 expression with elevated basal autophagy, and LAMP3 knockdown re-sensitizes them to tamoxifen, establishing LAMP3 as a modulator of autophagy contributing to tamoxifen resistance. siRNA knockdown, clonogenic assay, qRT-PCR, Western blot for LC3B and p62, tamoxifen-resistant cell culture Endocrine-related cancer Medium 24434718
2015 LAMP3 expression is strongly induced upon proteasomal inhibition in neuroblastoma SH-SY5Y cells via ATF4 signaling, and prevention of this LAMP3 induction enhances apoptotic cell death; LAMP3 induction increases autophagic flux, suggesting that LAMP3 serves as a compensatory survival mechanism during proteasomal dysfunction. siRNA knockdown, proteasomal inhibitor treatment, qRT-PCR, cell viability/apoptosis assays, autophagic flux measurement European journal of cell biology Medium 25681212
2016 LAMP3 overexpression in HCC cells activates Akt and upregulates lipogenic enzymes FASN and SCD-1, leading to increased intracellular lipid droplet and triglyceride accumulation; this effect is attenuated by PI3K/Akt pathway inhibition, placing LAMP3 upstream of PI3K/Akt in hepatic lipid metabolism regulation. LAMP3 overexpression in HepG2 cells, PI3K/Akt inhibitor treatment, Western blot for Akt/FASN/SCD-1, lipid droplet staining, triglyceride measurement Molecular and cellular endocrinology Medium 29056532
2016 Vitamin D3 reduces LAMP3 mRNA and protein expression during dendritic cell differentiation and maturation via the NF-κB pathway. Monocyte-derived DC differentiation, Vitamin D3 treatment, qRT-PCR, Western blot, NF-κB pathway analysis Cellular immunology Low 27697285
2016 LAMP3 is recruited to Salmonella-containing vacuoles (SCVs) alongside LAMP-2 upon infection, shifting from cell surface to pathogen-adjacent localization; LAMP3 knockdown by siRNA decreases the number of viable intracellular Salmonella recovered from infected THP-1 macrophage cells, establishing a pro-bacterial intracellular proliferation role. siRNA knockdown, confocal super-resolution N-SIM imaging, intracellular bacterial recovery assay, DNA microarray, LPS stimulation Molecules and cells Medium 27329040
2020 ATF4 directly regulates LAMP3 gene transcription: siRNA knockdown of ATF4 reduces LAMP3 mRNA, exogenous ATF4 overexpression upregulates LAMP3 mRNA, ChIP assays confirm ATF4 binding to the LAMP3 promoter, and dual-luciferase assay demonstrates that the ATF4-binding site is required for transcriptional upregulation. siRNA knockdown, cDNA overexpression, ChIP assay, dual-luciferase reporter assay The Journal of biological chemistry High 32312748
2020 LAMP3 expression induces epithelial cell apoptosis and causes accumulation and release of autoantigens TRIM21 (SSA), La (SSB), and α-fodrin via extracellular vesicles through an apoptosis-independent mechanism. In vitro LAMP3 overexpression in salivary gland epithelial cells, apoptosis assays, Western blot, extracellular vesicle isolation and analysis Scientific reports Medium 32939030
2020 LAMP3 depletion in esophageal squamous cell carcinoma cells increases phosphorylation of VASP at Ser239 via cAMP-dependent protein kinase A (PKA); silencing PKA regulatory subunits diminishes Ser239 phosphorylation and restores motility in LAMP3-depleted cells, identifying a LAMP3→PKA→VASP(Ser239) signaling axis controlling cell motility. siRNA knockdown of LAMP3 and PKA subunits, phospho-VASP Western blot, transwell migration assay, in vivo metastasis model Cancer letters Medium 32200035
2021 LAMP3 overexpression inhibits autophagic flux and causes lysosomal membrane permeabilization (LMP) leading to cell death; cathepsin B and D are released from lysosomes, and caspase 1 and caspase 3 are activated downstream. Stable LAMP3 overexpression cell lines (A253, HSG), autophagy flux assays (chloroquine, LC3 markers), galectin-3 puncta assay for LMP, caspase activity assays, cathepsin release measurement Autophagy Medium 34802379
2021 LAMP3 knockout mice generated by CRISPR/Cas9 show strongly increased lung SP-C levels and altered bronchoalveolar lavage lipid composition with changes in surfactant functionality, establishing LAMP3 as a regulator of pulmonary surfactant homeostasis in lamellar bodies of alveolar type II cells. CRISPR/Cas9 knockout mouse, surfactant protein quantification, BAL lipid composition analysis, lung function measurement, ovalbumin-induced asthma model PLoS genetics High 34161347
2020 A recessive missense variant (E387K) in LAMP3, located in the LAMP domain adjacent to a conserved disulfide bond, causes maturation arrest in lamellar body formation in alveolar type II cells, demonstrating that LAMP3 is required for normal lamellar body biogenesis. Genome-wide association study + whole exome sequencing in affected dogs, transmission electron microscopy of lung tissue, genetic mapping PLoS genetics Medium 32150563
2022 LAMP3 overexpression promotes endolysosomal degradation of NKCC1 and AQP5 (membrane proteins required for salivation), decreasing their expression levels and causing salivary gland hypofunction; LAMP3 overexpression also enhances AAV2 internalization via the promoted endolysosomal pathway. LAMP3 overexpression mouse model, Western blot for NKCC1/AQP5, salivary flow measurement, AAV2 gene transfer experiments, retrograde cannulation Scientific reports Medium 36329045
2022 During KSHV lytic replication, viral protein ORF45 activates eIF2α phosphorylation and ATF4 translation, leading to ATF4-dependent upregulation of LAMP3; elevated LAMP3 in turn activates Akt and ERK to facilitate lytic gene expression and virion production; LAMP3 silencing attenuates ATF4-promoted lytic replication, but LAMP3 acts independently of ATF4 expression. LAMP3 siRNA knockdown, ATF4 overexpression/knockdown, Western blot for Akt/ERK activation, viral gene expression assays, virion production measurement Journal of virology Medium 36377873
2022 LAMP3 overexpression in vaginal epithelial cells enhances HSV-2 replication, while LAMP3 knockout markedly attenuates virus production; HSV-2 colocalizes with LAMP3 in early endosomes and lysosomes, and blocking endosomal maturation or late endosomal/lysosomal fusion reduces HSV-2 replication. LAMP3 OE and KO cell lines (VK2), air-liquid interface culture, HSV-2 infection, virion quantification, fluorescence microscopy, pharmacological endosomal inhibitors Journal of virology Medium 36350153
2023 LAMP3 is packaged into extracellular particles (EPs) and transferred from LAMP3-overexpressing cells to naïve cells; internalization of LAMP3-containing EPs or recombinant LAMP3 protein induces caspase-dependent apoptosis in recipient cells, establishing a cell-to-cell communication role for extracellular LAMP3. Live-cell imaging, extracellular particle isolation, proteomics, recombinant LAMP3 protein internalization assay, caspase inhibitor experiments, Xfect transfection complex Scientific reports Medium 36788255
2023 RPL21 directly binds to the aa 341-416 domain of LAMP3 via its aa 1-40 and aa 111-160 segments; the RPL21-LAMP3 interaction stabilizes RPL21 protein by suppressing ubiquitin-proteasome degradation; together RPL21 and LAMP3 activate the FAK/paxillin/ERK signaling pathway to promote immature focal adhesion formation and CRC invasion. GST/His pull-down assay (domain mapping), Co-IP, ubiquitin-proteasome assay, immunofluorescence of focal adhesions, in vivo orthotopic metastasis model Cellular & molecular biology letters Medium 37062845
2023 USP4 interacts with LAMP3 (shown by Co-IP) and positively regulates LAMP3 expression in colorectal cancer cells; USP4 knockdown reduces LAMP3 expression and suppresses CRC cell proliferation and invasion, effects reversed by LAMP3 overexpression. Co-immunoprecipitation, siRNA knockdown, Western blot, cell proliferation/invasion assays, xenograft tumor model, IHC Naunyn-Schmiedeberg's archives of pharmacology Low 37728623
2025 Bi-allelic LAMP3 variants (frameshift Y302Qfs*2 causing nonsense-mediated mRNA decay, and T268M causing impaired N-glycosylation and protein instability) are associated with childhood interstitial lung disease; co-immunoprecipitation demonstrates a direct interaction between LAMP3 and surfactant proteins SP-B and SP-C, revealing a link between LAMP3 and surfactant metabolism. Exome sequencing, mRNA analysis (NMD), immunofluorescence, co-immunoprecipitation (LAMP3 with SP-B and SP-C), immunohistochemistry, in vitro expression of mutant LAMP3 EBioMedicine Medium 40023045
2025 LAMP3 inhibits autophagy in microglia and neurons by activating the NF-κB pathway during cerebral ischemia-reperfusion; LAMP3 overexpression in the MCAO/R mouse model inhibits autophagy and exacerbates brain tissue damage, while LAMP3 promotes oxidative stress and inflammatory cytokine release (IL-6, TNF-α). OGD/R model, MCAO/R mouse model, LAMP3 overexpression, Western blot, immunohistochemistry, TEM, confocal microscopy, ROS/LDH assays, rapamycin and BAY 11-7082 (NF-κB inhibitor) pharmacological rescue Cellular signalling Medium 39954716
2024 KDM6A upregulates LAMP3 expression via demethylation of H3K27me3 at the LAMP3 locus; KDM6A knockdown reduces LAMP3 expression and suppresses pancreatic cancer cell angiogenesis and invasion, effects reversed by LAMP3 overexpression. KDM6A siRNA knockdown, LAMP3 overexpression, Western blot for H3K27me3, tube formation assay, transwell assay Critical reviews in eukaryotic gene expression Low 39180205
2025 c-Myc binds to the promoter region of LAMP3 and positively regulates its transcription, as confirmed by dual-luciferase reporter gene assay; LAMP3 knockdown attenuates TSCC cell proliferation, DNA replication, metastatic capacity, and induces glucose metabolism reprogramming. Dual-luciferase reporter assay, bioinformatic prediction of transcription factor binding, siRNA knockdown, biological function assays, xenograft tumor model Scientific reports Medium 40450055
2010 ABCA3, a lipid transporter required for surfactant biogenesis, is N-terminally cleaved by a cysteine protease inside LAMP3-positive vesicles (multivesicular bodies/lamellar bodies), as demonstrated using N- and C-terminal protein tags and protease inhibition. N- and C-terminal protein tagging, cysteine protease inhibition, immunoblot, subcellular fractionation in LAMP3-positive vesicles FEBS letters Medium 20863830
2008 LAMP3 (but not LAMP1) participates in M180 amelogenin uptake: blocking LAMP3 with antibody decreases M180 amelogenin uptake in dental epithelial cells; siRNA knockdown of LAMP1 does not affect M180 amelogenin uptake, indicating LAMP3 is related to amelogenin degradation while LAMP1 is specific for smaller LRAP amelogenin. Anti-LAMP3 antibody blocking, siRNA knockdown of LAMP1/LAMP3, amelogenin uptake assay, mRNA induction assay Journal of biochemistry Low 18676354

Source papers

Stage 0 corpus · 76 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 A novel lysosome-associated membrane glycoprotein, DC-LAMP, induced upon DC maturation, is transiently expressed in MHC class II compartment. Immunity 313 9768752
2000 The tetraspanin CD63/lamp3 cycles between endocytic and secretory compartments in human endothelial cells. Molecular biology of the cell 258 10793155
2013 Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response. Breast cancer research : BCR 189 23294542
2008 Rheumatoid arthritis synovium contains two subsets of CD83-DC-LAMP- dendritic cells with distinct cytokine profiles. The American journal of pathology 120 18292234
2013 Hypoxic activation of the PERK/eIF2α arm of the unfolded protein response promotes metastasis through induction of LAMP3. Clinical cancer research : an official journal of the American Association for Cancer Research 111 24045183
2021 LAMP3 inhibits autophagy and contributes to cell death by lysosomal membrane permeabilization. Autophagy 101 34802379
2013 The PERK/ATF4/LAMP3-arm of the unfolded protein response affects radioresistance by interfering with the DNA damage response. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 92 23891100
2004 Selective accumulation of mature DC-Lamp+ dendritic cells in tumor sites is associated with efficient T-cell-mediated antitumor response and control of metastatic dissemination in melanoma. Cancer research 90 15026362
2005 Overexpression of LAMP3/TSC403/DC-LAMP promotes metastasis in uterine cervical cancer. Cancer research 89 16204031
2014 LAMP3 is involved in tamoxifen resistance in breast cancer cells through the modulation of autophagy. Endocrine-related cancer 86 24434718
2009 Hypoxic activation of the unfolded protein response (UPR) induces expression of the metastasis-associated gene LAMP3. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 81 19726095
2004 CD208/dendritic cell-lysosomal associated membrane protein is a marker of normal and transformed type II pneumocytes. The American journal of pathology 66 14982840
2017 LAMP3 regulates hepatic lipid metabolism through activating PI3K/Akt pathway. Molecular and cellular endocrinology 60 29056532
2004 LAMP-1 and LAMP-2, but not LAMP-3, are reliable markers for activation-induced secretion of human mast cells. Cytometry. Part A : the journal of the International Society for Analytical Cytology 60 15351990
2023 Interactions of Indoleamine 2,3-dioxygenase-expressing LAMP3+ dendritic cells with CD4+ regulatory T cells and CD8+ exhausted T cells: synergistically remodeling of the immunosuppressive microenvironment in cervical cancer and therapeutic implications. Cancer communications (London, England) 59 37794698
2007 Long-term protective effect of mature DC-LAMP+ dendritic cell accumulation in sentinel lymph nodes containing micrometastatic melanoma. Clinical cancer research : an official journal of the American Association for Cancer Research 59 17606713
2020 LAMP3 induces apoptosis and autoantigen release in Sjögren's syndrome patients. Scientific reports 51 32939030
2019 Long noncoding RNA HAGLR acts as a microRNA-143-5p sponge to regulate epithelial-mesenchymal transition and metastatic potential in esophageal cancer by regulating LAMP3. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 48 31311326
2003 Differential expression of CCL19 by DC-Lamp+ mature dendritic cells in human lymph node versus chronically inflamed skin. The Journal of pathology 48 12474232
2024 Interactions between LAMP3+ dendritic cells and T-cell subpopulations promote immune evasion in papillary thyroid carcinoma. Journal for immunotherapy of cancer 35 38816233
2023 RPL21 interacts with LAMP3 to promote colorectal cancer invasion and metastasis by regulating focal adhesion formation. Cellular & molecular biology letters 33 37062845
2015 Loss of lysosome-associated membrane protein 3 (LAMP3) enhances cellular vulnerability against proteasomal inhibition. European journal of cell biology 33 25681212
2010 The surfactant lipid transporter ABCA3 is N-terminally cleaved inside LAMP3-positive vesicles. FEBS letters 33 20863830
2003 Cloning and characterization of the mouse homologue of the human dendritic cell maturation marker CD208/DC-LAMP. European journal of immunology 31 12938238
2014 Hypoxic regulation of the PERK/ATF4/LAMP3-arm of the unfolded protein response in head and neck squamous cell carcinoma. Head & neck 29 24634103
2012 Characterisation and expression analysis of the rainbow trout (Oncorhynchus mykiss) homologue of the human dendritic cell marker CD208/lysosomal associated membrane protein 3. Developmental and comparative immunology 28 22402276
2016 Vitamin D3 regulates LAMP3 expression in monocyte derived dendritic cells. Cellular immunology 24 27697285
2020 The gene for the lysosomal protein LAMP3 is a direct target of the transcription factor ATF4. The Journal of biological chemistry 23 32312748
2017 LAMP3 promotes the invasion of osteosarcoma cells via SPP1 signaling. Molecular medicine reports 21 28849219
2016 LAMP-3 (Lysosome-Associated Membrane Protein 3) Promotes the Intracellular Proliferation of Salmonella typhimurium. Molecules and cells 20 27329040
2013 Clinical and immunological implications of increase in CD208+ dendritic cells in tonsils of patients with immunoglobulin A nephropathy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20 24081865
2021 A Genome-wide Association Study Identifies SERPINB10, CRLF3, STX7, LAMP3, IFNG-AS1, and KRT80 As Risk Loci Contributing to Cutaneous Leishmaniasis in Brazil. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 19 32830257
2022 Correction of LAMP3-associated salivary gland hypofunction by aquaporin gene therapy. Scientific reports 18 36329045
2020 Depletion of LAMP3 enhances PKA-mediated VASP phosphorylation to suppress invasion and metastasis in esophageal squamous cell carcinoma. Cancer letters 18 32200035
2021 LAMP3 deficiency affects surfactant homeostasis in mice. PLoS genetics 17 34161347
2017 LAMP3 expression correlated with poor clinical outcome in human ovarian cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 28349821
2008 The effects of LAMP1 and LAMP3 on M180 amelogenin uptake, localization and amelogenin mRNA induction by amelogenin protein. Journal of biochemistry 17 18676354
2021 Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder. Neurology 16 33397775
2007 Presence of mature DC-Lamp+ dendritic cells in sentinel and non-sentinel lymph nodes of breast cancer patients. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 16 17618075
2006 Depletion of alveolar glycogen corresponds with immunohistochemical development of CD208 antigen expression in perinatal lamb lung. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 16 16899762
2016 The potential role of lysosome-associated membrane protein 3 (LAMP3) on cardiac remodelling. American journal of translational research 15 27069538
2009 Cloning and characterisation of the chicken orthologue of dendritic cell-lysosomal associated membrane protein (DC-LAMP). Developmental and comparative immunology 15 19782701
2011 Significance of DC-LAMP and DC-SIGN expression in psoriasis vulgaris lesions. Experimental and molecular pathology 14 21596034
2020 Recessive missense LAMP3 variant associated with defect in lamellar body biogenesis and fatal neonatal interstitial lung disease in dogs. PLoS genetics 13 32150563
2018 LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53. Cellular & molecular biology letters 13 30008754
2014 Increase of DC-LAMP+ mature dendritic cell subsets in dermatopathic lymphadenitis of mycosis fungoides. European journal of dermatology : EJD 12 25672788
2010 Lumenal part of the DC-LAMP protein is not required for induction of antigen-specific T cell responses by means of antigen-DC-LAMP messenger RNA-electroporated dendritic cells. Human gene therapy 11 19903083
2009 Increased expression of CD208 (DC-LAMP) in epidermal keratinocytes of psoriatic lesions. The Journal of dermatology 11 19335688
2023 Curcumin inhibits the development of colorectal cancer via regulating the USP4/LAMP3 pathway. Naunyn-Schmiedeberg's archives of pharmacology 9 37728623
2020 FOXP3, CD208, and CD206 Expression in Canine Cutaneous Histiocytoma. Veterinary pathology 9 32783525
2013 DC-LAMP+ dendritic cells are recruited to gastric lymphoid follicles in Helicobacter pylori-infected individuals. Infection and immunity 9 23876802
2025 Bi-allelic LAMP3 variants in childhood interstitial lung disease: a surfactant-related disease. EBioMedicine 8 40023045
2023 Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren's disease. PloS one 8 36821638
2023 LAMP3 expression in the liver is involved in T cell activation and adaptive immune regulation in hepatitis B virus infection. Frontiers in immunology 8 37006307
2022 Upregulation of ATF4-LAMP3 Axis by ORF45 Facilitates Lytic Replication of Kaposi's Sarcoma-Associated Herpesvirus. Journal of virology 8 36377873
2014 Association analysis of STK39, MCCC1/LAMP3 and sporadic PD in the Chinese Han population. Neuroscience letters 8 24631562
2025 LAMP3 exacerbates autophagy-mediated neuronal damage through NF-kB in microglia. Cellular signalling 6 39954716
2019 Efficacy of radiation exposure in laryngeal squamous cell carcinoma is mediated by the LAMP3/LAMC2/tenascin-C pathway. Experimental biology and medicine (Maywood, N.J.) 6 31390898
2006 DC-LAMP stains pulmonary adenocarcinoma with bronchiolar Clara cell differentiation. Human pathology 6 17056097
2023 LAMP3 transfer via extracellular particles induces apoptosis in Sjögren's disease. Scientific reports 5 36788255
2023 MiR-526b-3p enhances sensitivity of head and neck squamous cell carcinoma cells to radiotherapy via suppressing exosomal LAMP3-mediated autophagy. Autoimmunity 5 37740656
2022 LAMP3/CD63 Expression in Early and Late Endosomes in Human Vaginal Epithelial Cells Is Associated with Enhancement of HSV-2 Infection. Journal of virology 5 36350153
2014 Accumulation of CD208⁺ mature dendritic cells does not correlate with survival time in oral squamous cell carcinoma patients. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 5 25149675
2025 LAMP3-mediated epithelial-mesenchymal transition promotes the invasion and excessive proliferation of fibroblast-like synoviocytes in rheumatoid arthritis. Journal of autoimmunity 4 39799877
2024 Potential Plasma Proteins (LGALS9, LAMP3, PRSS8 and AGRN) as Predictors of Hospitalisation Risk in COVID-19 Patients. Biomolecules 4 39334929
2023 Inhibition of LAMP3 mediates the protective effect of vitamin D against hypoxia/reoxygenation in trophoblast cells. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 4 37878884
2021 Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson's disease in patients of Malay ancestry. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 4 33559030
2025 Long non-coding RNA C1RL-AS1 aggravates influenza A virus pneumonia through miR-16-5p/LAMP3. Virus genes 2 39747803
2025 USF2-Mediated Transcription of BZW2 Contributes to CRC Malignant Progression by Affecting LAMP3. The journal of gene medicine 1 40112348
2025 c-Myc-dependent LAMP3 regulates the proliferation, metastasis and metabolic reprogramming of tongue squamous cell carcinoma. Scientific reports 1 40450055
2024 KDM6A Promotes Angiogenesis, Migration, and Invasion of Pancreatic Cancer by Activating LAMP3. Critical reviews in eukaryotic gene expression 1 39180205
2026 PERK/ATF4/LAMP3-arm contributes to the aggressive phenotype of hepatocellular carcinoma cells in response to the chronic ethanol exposure. Scientific reports 0 41582194
2026 Biallelic LAMP3 variants in 5 families with interstitial lung disease: Evidence of a disease-gene association. Genetics in medicine : official journal of the American College of Medical Genetics 0 41653023
2026 IL-31 blockade elevates thymus and activation-regulated chemokine by lifting LAMP3+CD1c+ mature dendritic cells from calcitonin gene-related peptide-calcitonin receptor-like neuroimmune suppression in atopic dermatitis. The Journal of allergy and clinical immunology 0 41831623
2025 LAMP3 signature affects cervical cancer progression through autophagy. BMC cancer 0 40707912
2024 Lysosome-Associated Membrane Protein-3 (LAMP3) Expression in Oral Squamous Cell Carcinoma and Its Relationship With Clinicopathological Parameters: A Cross-Sectional Study. Cureus 0 39429383

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