LAMP3

UniProt ID: Q9UQV4
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

LAMP3 (DC-LAMP, CD208) is a single-pass type I glycoprotein of the LAMP family with a heavily glycosylated luminal domain containing a single LAMP domain and a short cytoplasmic tail with a lysosomal targeting motif. Unlike the ubiquitous LAMP1/LAMP2 it is expressed in restricted cell types, notably mature interdigitating dendritic cells (where it is strongly induced on activation), alveolar type II pneumocytes (in the limiting membrane of surfactant-storing lamellar bodies), activated B cells and many carcinomas. In dendritic cells it appears in MHC class II compartments before MHC II is transferred to the cell surface and then concentrates in perinuclear lysosomes. It resides mainly in lysosomal and late endosomal membranes, with a small cell-surface pool. Reported roles include promoting autophagic flux as an ATF4/UPR target, supporting influenza A virus post-entry replication and Salmonella intracellular growth, but its molecular activity is not defined.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005765 lysosomal membrane
EXP
PMID:21930964
Reciprocal polarization of T and B cells at the immunologica...
ACCEPT
Summary: LAMP3 is a lysosomal membrane glycoprotein in dendritic cells and other cell types.
Reason: Confocal microscopy shows lysosomal distribution in dendritic cells; LAMP3 is a type I membrane protein of the LAMP family with a lysosomal targeting tail.
Supporting Evidence:
PMID:9768752
Confocal microscopy confirmed the lysosomal distribution of the protein.
PMID:9768752
DC-LAMP was found in the MHC class II compartment immediately before the translocation of MHC class II molecules to the cell surface, after which it concentrates into perinuclear lysosomes.
GO:0005765 lysosomal membrane
EXP
PMID:9768752
A novel lysosome-associated membrane glycoprotein, DC-LAMP, ...
ACCEPT
Summary: LAMP3 is a lysosomal membrane glycoprotein in dendritic cells and other cell types.
Reason: Confocal microscopy shows lysosomal distribution in dendritic cells; LAMP3 is a type I membrane protein of the LAMP family with a lysosomal targeting tail.
Supporting Evidence:
PMID:9768752
Confocal microscopy confirmed the lysosomal distribution of the protein.
PMID:9768752
DC-LAMP was found in the MHC class II compartment immediately before the translocation of MHC class II molecules to the cell surface, after which it concentrates into perinuclear lysosomes.
GO:0005765 lysosomal membrane
IBA
GO_REF:0000033
ACCEPT
Summary: LAMP3 is a lysosomal membrane glycoprotein in dendritic cells and other cell types.
Reason: Confocal microscopy shows lysosomal distribution in dendritic cells; LAMP3 is a type I membrane protein of the LAMP family with a lysosomal targeting tail.
Supporting Evidence:
PMID:9768752
Confocal microscopy confirmed the lysosomal distribution of the protein.
PMID:9768752
DC-LAMP was found in the MHC class II compartment immediately before the translocation of MHC class II molecules to the cell surface, after which it concentrates into perinuclear lysosomes.
GO:0005765 lysosomal membrane
IEA
GO_REF:0000044
ACCEPT
Summary: LAMP3 is a lysosomal membrane glycoprotein in dendritic cells and other cell types.
Reason: Confocal microscopy shows lysosomal distribution in dendritic cells; LAMP3 is a type I membrane protein of the LAMP family with a lysosomal targeting tail.
Supporting Evidence:
PMID:9768752
Confocal microscopy confirmed the lysosomal distribution of the protein.
PMID:9768752
DC-LAMP was found in the MHC class II compartment immediately before the translocation of MHC class II molecules to the cell surface, after which it concentrates into perinuclear lysosomes.
GO:0005765 lysosomal membrane
TAS
PMID:9721848
Isolation and characterization of a novel human lung-specifi...
ACCEPT
Summary: LAMP3 is a lysosomal membrane glycoprotein in dendritic cells and other cell types.
Reason: Confocal microscopy shows lysosomal distribution in dendritic cells; LAMP3 is a type I membrane protein of the LAMP family with a lysosomal targeting tail.
Supporting Evidence:
PMID:9768752
Confocal microscopy confirmed the lysosomal distribution of the protein.
PMID:9768752
DC-LAMP was found in the MHC class II compartment immediately before the translocation of MHC class II molecules to the cell surface, after which it concentrates into perinuclear lysosomes.
GO:0005769 early endosome
IDA
PMID:21810281
Lysosome-associated membrane glycoprotein 3 is involved in i...
MODIFY
Summary: LAMP3-positive vesicles colocalize with incoming influenza NP early in infection.
Reason: LAMP3 is a membrane protein, so the early endosome membrane term already carried is the precise form; the endosomal localization is retained as non-core.
Proposed replacements: early endosome membrane
Supporting Evidence:
PMID:21810281
LAMP3 is an influenza A virus inducible gene, and plays an important role in viral post-entry steps.
GO:0005886 plasma membrane
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: A pool of LAMP3 is present at the cell surface.
Reason: LAMP3 was observed at the surface of THP-1 macrophages before relocalizing to Salmonella vacuoles, and LAMP proteins cycle via the plasma membrane; the surface pool is minor relative to lysosomes, with the glycosylated luminal domain facing outward.
Supporting Evidence:
PMID:27329040
LAMP-3, like LAMP-2, shifts its localization from the cell surface to alongside Salmonella.
GO:0005886 plasma membrane
IDA
PMID:21810281
Lysosome-associated membrane glycoprotein 3 is involved in i...
KEEP AS NON CORE
Summary: A pool of LAMP3 is present at the cell surface.
Reason: LAMP3 was observed at the surface of THP-1 macrophages before relocalizing to Salmonella vacuoles, and LAMP proteins cycle via the plasma membrane; the surface pool is minor relative to lysosomes, with the glycosylated luminal domain facing outward.
Supporting Evidence:
PMID:27329040
LAMP-3, like LAMP-2, shifts its localization from the cell surface to alongside Salmonella.
GO:0009986 cell surface
EXP
PMID:27329040
LAMP-3 (Lysosome-Associated Membrane Protein 3) Promotes the...
KEEP AS NON CORE
Summary: A pool of LAMP3 is present at the cell surface.
Reason: LAMP3 was observed at the surface of THP-1 macrophages before relocalizing to Salmonella vacuoles, and LAMP proteins cycle via the plasma membrane; the surface pool is minor relative to lysosomes, with the glycosylated luminal domain facing outward.
Supporting Evidence:
PMID:27329040
LAMP-3, like LAMP-2, shifts its localization from the cell surface to alongside Salmonella.
GO:0009986 cell surface
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: A pool of LAMP3 is present at the cell surface.
Reason: LAMP3 was observed at the surface of THP-1 macrophages before relocalizing to Salmonella vacuoles, and LAMP proteins cycle via the plasma membrane; the surface pool is minor relative to lysosomes, with the glycosylated luminal domain facing outward.
Supporting Evidence:
PMID:27329040
LAMP-3, like LAMP-2, shifts its localization from the cell surface to alongside Salmonella.
GO:0010506 regulation of autophagy
IMP
PMID:25681212
Loss of lysosome-associated membrane protein 3 (LAMP3) enhan...
KEEP AS NON CORE
Summary: LAMP3 induction promotes autophagic flux during proteasome inhibition.
Reason: As an ATF4/UPR target LAMP3 supports autophagic flux and survival; the mechanism is undefined.
Supporting Evidence:
PMID:25681212
Induction of LAMP3 mRNA following proteasomal inhibition was dependent on UPR transcription factor ATF4 signaling and induced autophagic flux.
GO:0010628 positive regulation of gene expression
IMP
PMID:23651994
Gene network reconstruction reveals cell cycle and antiviral...
KEEP AS NON CORE
Summary: LAMP3 positively regulates interferon-dependent antiviral gene expression in cervical cancer cells.
Reason: The full text shows siRNA knockdown of LAMP3 in HeLa cells reduced interferon-dependent antiviral gene expression (STAT1, IRF7, HERC5, ISG20, OAS1), identifying LAMP3 as a positive regulator of this gene-expression program; this is a genuine but cancer-context, mechanism-undefined role peripheral to LAMP3's core lysosomal/lamellar-body membrane function.
Supporting Evidence:
PMID:23651994
LAMP3 drives the IFN-dependent gene expression signature
GO:0012505 endomembrane system
IEA
GO_REF:0000117
MODIFY
Summary: General membrane assignment.
Reason: True but general; LAMP3 is an integral protein of lysosomal membranes, already accepted.
Proposed replacements: lysosomal membrane
Supporting Evidence:
PMID:9768752
Confocal microscopy confirmed the lysosomal distribution of the protein.
GO:0016020 membrane
IEA
GO_REF:0000002
MODIFY
Summary: General membrane assignment.
Reason: True but general; LAMP3 is an integral protein of lysosomal membranes, already accepted.
Proposed replacements: lysosomal membrane
Supporting Evidence:
PMID:9768752
Confocal microscopy confirmed the lysosomal distribution of the protein.
GO:0030659 cytoplasmic vesicle membrane
EXP
PMID:9768752
A novel lysosome-associated membrane glycoprotein, DC-LAMP, ...
KEEP AS NON CORE
Summary: LAMP3 is in cytoplasmic vesicle membranes, including MHC class II compartments.
Reason: Supported by dendritic cell localization to MHC II-containing vesicles; the lysosomal and late endosomal membrane terms are more precise for the main pool.
Supporting Evidence:
PMID:9768752
DC-LAMP was found in the MHC class II compartment immediately before the translocation of MHC class II molecules to the cell surface, after which it concentrates into perinuclear lysosomes.
GO:0030659 cytoplasmic vesicle membrane
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: LAMP3 is in cytoplasmic vesicle membranes, including MHC class II compartments.
Reason: Supported by dendritic cell localization to MHC II-containing vesicles; the lysosomal and late endosomal membrane terms are more precise for the main pool.
Supporting Evidence:
PMID:9768752
DC-LAMP was found in the MHC class II compartment immediately before the translocation of MHC class II molecules to the cell surface, after which it concentrates into perinuclear lysosomes.
GO:0031901 early endosome membrane
EXP
PMID:21810281
Lysosome-associated membrane glycoprotein 3 is involved in i...
KEEP AS NON CORE
Summary: LAMP3 detected on early endosomal vesicles in lung epithelial cells.
Reason: Curated from imaging in influenza-infected A549 cells; a minor or transit location compared with lysosomes.
Supporting Evidence:
PMID:21810281
LAMP3 is an influenza A virus inducible gene, and plays an important role in viral post-entry steps.
GO:0031901 early endosome membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: LAMP3 detected on early endosomal vesicles in lung epithelial cells.
Reason: Curated from imaging in influenza-infected A549 cells; a minor or transit location compared with lysosomes.
Supporting Evidence:
PMID:21810281
LAMP3 is an influenza A virus inducible gene, and plays an important role in viral post-entry steps.
GO:0031902 late endosome membrane
IBA
GO_REF:0000033
ACCEPT
Summary: LAMP3 is in late endosome/MHC class II compartment membranes.
Reason: In dendritic cells LAMP3 occupies the MHC class II compartment, a late endosomal/lysosomal organelle, before reaching perinuclear lysosomes.
Supporting Evidence:
PMID:9768752
DC-LAMP was found in the MHC class II compartment immediately before the translocation of MHC class II molecules to the cell surface, after which it concentrates into perinuclear lysosomes.
GO:0031982 vesicle
IDA
PMID:25681212
Loss of lysosome-associated membrane protein 3 (LAMP3) enhan...
MODIFY
Summary: LAMP3-positive vesicles observed in cells.
Reason: LAMP3 is an integral membrane protein of these vesicles; the vesicle membrane term, already carried, is more precise.
Proposed replacements: cytoplasmic vesicle membrane
Supporting Evidence:
PMID:25681212
Induction of LAMP3 mRNA following proteasomal inhibition was dependent on UPR transcription factor ATF4 signaling and induced autophagic flux.
GO:0035455 response to interferon-alpha
IMP
PMID:23651994
Gene network reconstruction reveals cell cycle and antiviral...
KEEP AS NON CORE
Summary: LAMP3 participates in the cellular response to type I (alpha) interferon in cervical cancer cells.
Reason: The full text stimulated cells with interferon and showed LAMP3 knockdown altered the interferon-dependent antiviral gene signature (which the authors report as a mixed type I and type II IFN pattern); deferring to the curator's term, this GOA row annotates the type I (alpha) component, placing LAMP3 within the cellular response to type I (alpha) interferon. A genuine but non-core, cancer-context role distinct from LAMP3's structural lysosomal membrane function.
Supporting Evidence:
PMID:23651994
between LAMP3 siRNA and control siRNA treated HeLa cells after interferon stimulation
GO:0046718 symbiont entry into host cell
IMP NOT
PMID:21810281
Lysosome-associated membrane glycoprotein 3 is involved in i...
ACCEPT
Summary: Curated NOT annotation; LAMP3 is not involved in symbiont entry into the host cell.
Reason: This is a curated NOT (negated) annotation, and the evidence supports the negation. The study places the LAMP3 requirement at viral post-entry steps (NP nuclear accumulation), not entry, so the negation of symbiont entry is correct; keep it as the machine-readable record. LAMP3's actual effect is on later steps of the viral life cycle.
Supporting Evidence:
PMID:21810281
LAMP3 is an influenza A virus inducible gene, and plays an important role in viral post-entry steps.
GO:0048471 perinuclear region of cytoplasm
IDA
PMID:25681212
Loss of lysosome-associated membrane protein 3 (LAMP3) enhan...
KEEP AS NON CORE
Summary: LAMP3 concentrates in perinuclear lysosomes.
Reason: Consistent with the perinuclear lysosomal distribution in mature dendritic cells.
Supporting Evidence:
PMID:9768752
DC-LAMP was found in the MHC class II compartment immediately before the translocation of MHC class II molecules to the cell surface, after which it concentrates into perinuclear lysosomes.
GO:0072594 establishment of protein localization to organelle
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: Protein localization to organelle propagated from LAMP2 (chaperone-mediated autophagy).
Reason: The source activity is LAMP-2A's CMA receptor function, which depends on the LAMP-2A-specific cytosolic tail; there is no evidence that LAMP3 targets proteins to organelles.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: FUNCTIONAL DIVERGENCE
Sources checked:
MGI:MGI:96748 SUPPORTS SOURCE BUT NOT TARGET
Mouse Lamp2 CMA-related protein targeting; LAMP3 lacks the LAMP-2A cytosolic tail features for substrate binding.
Supporting Evidence:
PMID:9768752
Confocal microscopy confirmed the lysosomal distribution of the protein.
GO:0097233 alveolar lamellar body membrane
ISS
GO_REF:0000024
ACCEPT
Summary: LAMP3 is in the limiting membrane of lamellar bodies of alveolar type II cells (rat data).
Reason: LAMP3 is a characteristic marker of type II pneumocytes, where lamellar bodies are lysosome-related organelles; the transfer from rat is consistent with human lung expression of the gene.
Supporting Evidence:
PMID:9721848
We have isolated and characterized a novel human lung-specific gene
GO:0098588 bounding membrane of organelle
IEA
GO_REF:0000117
MODIFY
Summary: General membrane assignment.
Reason: True but general; LAMP3 is an integral protein of lysosomal membranes, already accepted.
Proposed replacements: lysosomal membrane
Supporting Evidence:
PMID:9768752
Confocal microscopy confirmed the lysosomal distribution of the protein.
GO:1901799 negative regulation of proteasomal protein catabolic process
IMP
PMID:25681212
Loss of lysosome-associated membrane protein 3 (LAMP3) enhan...
UNDECIDED
Summary: Link between LAMP3 and proteasomal degradation.
Reason: The cached abstract shows LAMP3 is induced by proteasome inhibition and promotes autophagic flux, not that LAMP3 negatively regulates proteasomal catabolism; the full-text basis for this IMP was not inspected.
Supporting Evidence:
PMID:25681212
Induction of LAMP3 mRNA following proteasomal inhibition was dependent on UPR transcription factor ATF4 signaling and induced autophagic flux.
GO:1903900 regulation of viral life cycle
IMP
PMID:21810281
Lysosome-associated membrane glycoprotein 3 is involved in i...
KEEP AS NON CORE
Summary: LAMP3 supports influenza A virus post-entry replication.
Reason: Knockdown reduced viral NP nuclear accumulation and titers; a host-factor role during infection.
Supporting Evidence:
PMID:21810281
LAMP3 is an influenza A virus inducible gene, and plays an important role in viral post-entry steps.

Core Functions

Lysosomal/late endosomal membrane glycoprotein of dendritic cells, B cells and alveolar type II cells (lamellar bodies), of undefined molecular activity, that modulates autophagic flux and the endolysosomal compartment during dendritic cell maturation and stress.

Supporting Evidence:
  • PMID:9768752
    Confocal microscopy confirmed the lysosomal distribution of the protein.
  • PMID:25681212
    Induction of LAMP3 mRNA following proteasomal inhibition was dependent on UPR transcription factor ATF4 signaling and induced autophagic flux.

References

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Suggested Questions for Experts

Q: What molecular activity does LAMP3 contribute to lamellar bodies and dendritic cell MHC class II compartments?

Suggested Experiments

Experiment: Profile lamellar body composition, surfactant secretion and MHC II peptide presentation in LAMP3-knockout alveolar type II cells and dendritic cells.

Type: knockout phenotyping

πŸ“š Additional Documentation

Notes

(LAMP3-notes.md)

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