LAMP1

UniProt ID: P11279
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

LAMP1 encodes lysosome-associated membrane glycoprotein 1, an abundant heavily glycosylated single-pass membrane protein of lysosomes, late endosomes, and lysosome-related secretory granules. Its most informative current molecular function is direct inhibition of the lysosomal TMEM175 cation/proton channel, supporting lysosomal lumen acidification and hydrolase activity. LAMP1 also participates in lysosome-related immune granule contexts, TAPL/ABCB9 stabilization, Lassa virus receptor activity, and plasma membrane exposure during degranulation, but its core biology is centered on lysosomal and late-endosomal membrane function.

Proposed New Ontology Terms

lysosomal proton channel inhibitor activity

Definition: An ion channel inhibitor activity that decreases the activity of a proton-conducting channel in the lysosomal membrane.

Justification: LAMP1 inhibits TMEM175 proton leak channel activity, but the current available GO term is only broad ion channel inhibitor activity.

Parent term: ion channel inhibitor activity

Supporting Evidence:

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005765 lysosomal membrane
IBA
GO_REF:0000033 		ACCEPT
Summary: LAMP1 is a canonical single-pass lysosomal membrane glycoprotein; this is the primary cellular location for its core lysosomal functions.
Reason: Retain as a core location for LAMP1, including the TMEM175-dependent lysosomal pH function.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0072594 establishment of protein localization to organelle
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Keep this broad protein-localization process as a non-core NK-cell lytic-granule context.
Reason: PMID:23632890 supports LAMP1-dependent perforin delivery to lytic granules and lytic-granule movement, but not the more specific Golgi-to-lysosome transport term.
Supporting Evidence:
PMID:23632890
LAMP1 silencing causes inhibition of NK-cell cytotoxicity
PMID:23632890
Reduction of LAMP1 expression affects the movement of lytic granules
PMID:23632890
perforin trafficking to lytic granules
GO:0005886 plasma membrane
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: plasma membrane is supported during LAMP1 cycling and cytotoxic granule exocytosis, but it is secondary to the lysosomal membrane location.
Reason: Retain as non-core surface/exocytic localization rather than the defining LAMP1 location.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0031902 late endosome membrane
IBA
GO_REF:0000033 		ACCEPT
Summary: LAMP1 shuttles through the endolysosomal system and is supported at the late endosome membrane.
Reason: Retain as a core endolysosomal membrane location closely related to the lysosomal membrane role.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0005765 lysosomal membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: LAMP1 is a canonical single-pass lysosomal membrane glycoprotein; this is the primary cellular location for its core lysosomal functions.
Reason: Retain as a core location for LAMP1, including the TMEM175-dependent lysosomal pH function.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0005829 cytosol
IEA
GO_REF:0000108 		REMOVE
Summary: cytosol is not an appropriate whole-protein location for a single-pass lysosomal membrane glycoprotein.
Reason: A cytosolic tail faces the cytosol, but the protein itself should be annotated to membranes rather than cytosol/cytoplasm.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Single-pass type I membrane protein
GO:0005886 plasma membrane
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: plasma membrane is supported during LAMP1 cycling and cytotoxic granule exocytosis, but it is secondary to the lysosomal membrane location.
Reason: Retain as non-core surface/exocytic localization rather than the defining LAMP1 location.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0007042 lysosomal lumen acidification
IEA
GO_REF:0000117 		ACCEPT
Summary: LAMP1 supports lysosomal lumen acidification by inhibiting the TMEM175 lysosomal cation/proton channel.
Reason: Retain as a core process supported by direct LAMP-TMEM175 functional evidence.
Supporting Evidence:
PMID:37390818
directly interact with and inhibit the activity of the lysosomal cation channel TMEM175
PMID:37390818
facilitates lysosomal acidification to a lower pH environment
file:human/LAMP1/LAMP1-uniprot.txt
Acts as a direct inhibitor of the proton channel TMEM175
GO:0008200 ion channel inhibitor activity
IEA
GO_REF:0000117 		ACCEPT
Summary: LAMP1 directly inhibits TMEM175 channel activity; GO currently represents this as broad ion channel inhibitor activity.
Reason: Retain as the best available molecular-function term for the TMEM175 inhibition mechanism.
Supporting Evidence:
PMID:37390818
directly interact with and inhibit the activity of the lysosomal cation channel TMEM175
PMID:37390818
facilitates lysosomal acidification to a lower pH environment
file:human/LAMP1/LAMP1-uniprot.txt
Acts as a direct inhibitor of the proton channel TMEM175
GO:0010008 endosome membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: LAMP1 shuttles through the endolysosomal system and is supported at the endosome membrane.
Reason: Retain as a core endolysosomal membrane location closely related to the lysosomal membrane role.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0016020 membrane
IEA
GO_REF:0000002 		MODIFY
Summary: membrane is true but too general for LAMP1.
Reason: Replace the broad membrane/vesicle term with lysosomal membrane, the informative core location.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0031902 late endosome membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: LAMP1 shuttles through the endolysosomal system and is supported at the late endosome membrane.
Reason: Retain as a core endolysosomal membrane location closely related to the lysosomal membrane role.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0035577 azurophil granule membrane
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: azurophil granule membrane is a supported lysosome-related secretory granule membrane context in immune cells.
Reason: Retain as cell-type-specific non-core localization.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0101003 ficolin-1-rich granule membrane
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: ficolin-1-rich granule membrane is a supported lysosome-related secretory granule membrane context in immune cells.
Reason: Retain as cell-type-specific non-core localization.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0101004 cytolytic granule membrane
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: cytolytic granule membrane is a supported lysosome-related secretory granule membrane context in immune cells.
Reason: Retain as cell-type-specific non-core localization.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0005515 protein binding
IPI
PMID:23394946
mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channe... 		MARK AS OVER ANNOTATED
Summary: The reported interaction evidence does not define a useful LAMP1 molecular function as generic protein binding.
Reason: Avoid retaining GO:0005515 when a more specific mechanism is absent or captured by another term.
Supporting Evidence:
file:human/LAMP1/LAMP1-notes.md
generic enzyme/protein-binding annotations are not informative
GO:0005515 protein binding
IPI
PMID:24970085
Virus entry. Lassa virus entry requires a trigger-induced re... 		MODIFY
Summary: LAMP1 binds Lassa virus glycoprotein in acidic endolysosomal compartments, but generic protein binding is not the informative term.
Reason: Use virus receptor activity for this host-pathogen context and keep it out of the core LAMP1 function summary.
Proposed replacements: virus receptor activity
Supporting Evidence:
PMID:24970085
involved a pH-dependent switch to an intracellular receptor
PMID:24970085
The resistance of Lamp1-deficient mice to Lassa virus highlights
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		MARK AS OVER ANNOTATED
Summary: The reported interaction evidence does not define a useful LAMP1 molecular function as generic protein binding.
Reason: Avoid retaining GO:0005515 when a more specific mechanism is absent or captured by another term.
Supporting Evidence:
file:human/LAMP1/LAMP1-notes.md
generic enzyme/protein-binding annotations are not informative
GO:0000421 autophagosome membrane
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Autophagosome membrane is likely an over-extension from autophagy/autolysosome contexts; LAMP1 is primarily lysosomal and autolysosomal after fusion.
Reason: Do not treat LAMP1 as a canonical autophagosome membrane protein without direct gene-specific evidence.
Supporting Evidence:
PMID:22885770
clathrin and phosphatidylinositol-4,5-bisphosphate
file:human/LAMP1/LAMP1-notes.md
PN membership alone is not evidence for a GO annotation
GO:0005764 lysosome
IEA
GO_REF:0000107 		MODIFY
Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein.
Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0005768 endosome
IEA
GO_REF:0000107 		MODIFY
Summary: Endosome is correct as a broad compartment, but LAMP1 is specifically an endosomal membrane protein.
Reason: Use endosome membrane to capture the integral membrane localization.
Proposed replacements: endosome membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0005770 late endosome
IEA
GO_REF:0000107 		MODIFY
Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane.
Reason: Use late endosome membrane to capture the integral membrane localization.
Proposed replacements: late endosome membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0005771 multivesicular body
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: multivesicular body is a plausible trafficking or lysosome-related context for LAMP1 but is not the defining location or function.
Reason: Retain as non-core context while prioritizing lysosomal/late endosomal membrane annotations.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0008021 synaptic vesicle
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: synaptic vesicle is a plausible trafficking or lysosome-related context for LAMP1 but is not the defining location or function.
Reason: Retain as non-core context while prioritizing lysosomal/late endosomal membrane annotations.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0009897 external side of plasma membrane
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: external side of plasma membrane is supported during LAMP1 cycling and cytotoxic granule exocytosis, but it is secondary to the lysosomal membrane location.
Reason: Retain as non-core surface/exocytic localization rather than the defining LAMP1 location.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0009986 cell surface
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: cell surface is supported during LAMP1 cycling and cytotoxic granule exocytosis, but it is secondary to the lysosomal membrane location.
Reason: Retain as non-core surface/exocytic localization rather than the defining LAMP1 location.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0019904 protein domain specific binding
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Protein domain specific binding is an uninformative automated transfer for LAMP1.
Reason: Do not retain broad binding terms without a specific functional mechanism.
Supporting Evidence:
file:human/LAMP1/LAMP1-notes.md
Generic enzyme/protein-binding annotations are not informative
GO:0031982 vesicle
IEA
GO_REF:0000107 		MODIFY
Summary: vesicle is true but too general for LAMP1.
Reason: Replace the broad membrane/vesicle term with lysosomal membrane, the informative core location.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0042383 sarcolemma
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: sarcolemma is a plausible trafficking or lysosome-related context for LAMP1 but is not the defining location or function.
Reason: Retain as non-core context while prioritizing lysosomal/late endosomal membrane annotations.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0042470 melanosome
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: melanosome is a plausible trafficking or lysosome-related context for LAMP1 but is not the defining location or function.
Reason: Retain as non-core context while prioritizing lysosomal/late endosomal membrane annotations.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0044194 cytolytic granule
IEA
GO_REF:0000107 		MODIFY
Summary: Cytolytic granule is a supported secretory-lysosome context, but LAMP1 is a membrane protein.
Reason: Use cytolytic granule membrane for the more precise compartment.
Proposed replacements: cytolytic granule membrane
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0044754 autolysosome
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: autolysosome is a plausible trafficking or lysosome-related context for LAMP1 but is not the defining location or function.
Reason: Retain as non-core context while prioritizing lysosomal/late endosomal membrane annotations.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0045335 phagocytic vesicle
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: phagocytic vesicle is a plausible trafficking or lysosome-related context for LAMP1 but is not the defining location or function.
Reason: Retain as non-core context while prioritizing lysosomal/late endosomal membrane annotations.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0050821 protein stabilization
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: LAMP1/LAMP2 stabilize TAPL/ABCB9 at the endosomal limiting membrane.
Reason: Retain as a supported secondary process rather than the core lysosomal pH function.
Supporting Evidence:
PMID:22641697
LAMP proteins retain TAPL on the limiting membrane of endosomes
PMID:22641697
In LAMP-deficient cells, the half-life of TAPL is decreased
GO:0061474 phagolysosome membrane
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: phagolysosome membrane is a plausible trafficking or lysosome-related context for LAMP1 but is not the defining location or function.
Reason: Retain as non-core context while prioritizing lysosomal/late endosomal membrane annotations.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0005515 protein binding
IPI
PMID:39284914
ER-phagy restrains inflammatory responses through its recept... 		MARK AS OVER ANNOTATED
Summary: The ER-phagy paper uses LAMP1-positive compartments and reports UBAC2 association with LAMP1, but LAMP1 is not the mechanistic receptor in that study.
Reason: Generic protein binding would overstate LAMP1 function; the study is mainly about UBAC2/GABARAP-mediated ER-phagy.
Supporting Evidence:
PMID:39284914
autophagy activation promoted the distribution of UBAC2 into LAMP1
GO:0005765 lysosomal membrane
EXP
PMID:17897319
Integral and associated lysosomal membrane proteins. 		ACCEPT
Summary: LAMP1 is a canonical single-pass lysosomal membrane glycoprotein; this is the primary cellular location for its core lysosomal functions.
Reason: Retain as a core location for LAMP1, including the TMEM175-dependent lysosomal pH function.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0005886 plasma membrane
EXP
PMID:2022921
Cytotoxic T lymphocyte granules are secretory lysosomes, con... 		KEEP AS NON CORE
Summary: plasma membrane is supported during LAMP1 cycling and cytotoxic granule exocytosis, but it is secondary to the lysosomal membrane location.
Reason: Retain as non-core surface/exocytic localization rather than the defining LAMP1 location.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0005886 plasma membrane
EXP
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from deg... 		KEEP AS NON CORE
Summary: plasma membrane is supported during LAMP1 cycling and cytotoxic granule exocytosis, but it is secondary to the lysosomal membrane location.
Reason: Retain as non-core surface/exocytic localization rather than the defining LAMP1 location.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0010008 endosome membrane
EXP
PMID:16176980
The oxysterol-binding protein homologue ORP1L interacts with... 		ACCEPT
Summary: LAMP1 shuttles through the endolysosomal system and is supported at the endosome membrane.
Reason: Retain as a core endolysosomal membrane location closely related to the lysosomal membrane role.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0031902 late endosome membrane
EXP
PMID:16176980
The oxysterol-binding protein homologue ORP1L interacts with... 		ACCEPT
Summary: LAMP1 shuttles through the endolysosomal system and is supported at the late endosome membrane.
Reason: Retain as a core endolysosomal membrane location closely related to the lysosomal membrane role.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0101004 cytolytic granule membrane
EXP
PMID:2022921
Cytotoxic T lymphocyte granules are secretory lysosomes, con... 		KEEP AS NON CORE
Summary: cytolytic granule membrane is a supported lysosome-related secretory granule membrane context in immune cells.
Reason: Retain as cell-type-specific non-core localization.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0005515 protein binding
IPI
PMID:37390818
Lysosomal LAMP proteins regulate lysosomal pH by direct inhi... 		MODIFY
Summary: The TMEM175 interaction is real, but generic protein binding hides the informative channel-inhibitor mechanism.
Reason: Replace with ion channel inhibitor activity for the LAMP1-TMEM175 functional interaction.
Proposed replacements: ion channel inhibitor activity
Supporting Evidence:
PMID:37390818
directly interact with and inhibit the activity of the lysosomal cation channel TMEM175
PMID:37390818
facilitates lysosomal acidification to a lower pH environment
file:human/LAMP1/LAMP1-uniprot.txt
Acts as a direct inhibitor of the proton channel TMEM175
GO:0005765 lysosomal membrane
IDA
PMID:16176980
The oxysterol-binding protein homologue ORP1L interacts with... 		ACCEPT
Summary: LAMP1 is a canonical single-pass lysosomal membrane glycoprotein; this is the primary cellular location for its core lysosomal functions.
Reason: Retain as a core location for LAMP1, including the TMEM175-dependent lysosomal pH function.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0007042 lysosomal lumen acidification
IDA
PMID:37390818
Lysosomal LAMP proteins regulate lysosomal pH by direct inhi... 		ACCEPT
Summary: LAMP1 supports lysosomal lumen acidification by inhibiting the TMEM175 lysosomal cation/proton channel.
Reason: Retain as a core process supported by direct LAMP-TMEM175 functional evidence.
Supporting Evidence:
PMID:37390818
directly interact with and inhibit the activity of the lysosomal cation channel TMEM175
PMID:37390818
facilitates lysosomal acidification to a lower pH environment
file:human/LAMP1/LAMP1-uniprot.txt
Acts as a direct inhibitor of the proton channel TMEM175
GO:0008200 ion channel inhibitor activity
IDA
PMID:37390818
Lysosomal LAMP proteins regulate lysosomal pH by direct inhi... 		ACCEPT
Summary: LAMP1 directly inhibits TMEM175 channel activity; GO currently represents this as broad ion channel inhibitor activity.
Reason: Retain as the best available molecular-function term for the TMEM175 inhibition mechanism.
Supporting Evidence:
PMID:37390818
directly interact with and inhibit the activity of the lysosomal cation channel TMEM175
PMID:37390818
facilitates lysosomal acidification to a lower pH environment
file:human/LAMP1/LAMP1-uniprot.txt
Acts as a direct inhibitor of the proton channel TMEM175
GO:0005764 lysosome
IDA
PMID:25365221
Spastic paraplegia proteins spastizin and spatacsin mediate ... 		MODIFY
Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein.
Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0005515 protein binding
IPI
PMID:21194361
The lysosomal polypeptide transporter TAPL: more than a hous... 		MARK AS OVER ANNOTATED
Summary: The reported interaction evidence does not define a useful LAMP1 molecular function as generic protein binding.
Reason: Avoid retaining GO:0005515 when a more specific mechanism is absent or captured by another term.
Supporting Evidence:
file:human/LAMP1/LAMP1-notes.md
generic enzyme/protein-binding annotations are not informative
GO:0101004 cytolytic granule membrane
IDA
PMID:24088571
Arf-like GTPase Arl8b regulates lytic granule polarization a... 		KEEP AS NON CORE
Summary: cytolytic granule membrane is a supported lysosome-related secretory granule membrane context in immune cells.
Reason: Retain as cell-type-specific non-core localization.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0140507 granzyme-mediated programmed cell death signaling pathway
IMP
PMID:23632890
LAMP1/CD107a is required for efficient perforin delivery to ... 		KEEP AS NON CORE
Summary: granzyme-mediated programmed cell death signaling pathway is supported in NK-cell cytotoxicity assays but is cell-type-specific.
Reason: Retain as non-core immune-cell biology rather than the general LAMP1 core function.
Supporting Evidence:
PMID:23632890
LAMP1 silencing causes inhibition of NK-cell cytotoxicity
PMID:23632890
Reduction of LAMP1 expression affects the movement of lytic granules
GO:1902513 regulation of organelle transport along microtubule
IMP
PMID:23632890
LAMP1/CD107a is required for efficient perforin delivery to ... 		KEEP AS NON CORE
Summary: regulation of organelle transport along microtubule is supported in NK-cell cytotoxicity assays but is cell-type-specific.
Reason: Retain as non-core immune-cell biology rather than the general LAMP1 core function.
Supporting Evidence:
PMID:23632890
LAMP1 silencing causes inhibition of NK-cell cytotoxicity
PMID:23632890
Reduction of LAMP1 expression affects the movement of lytic granules
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-6798739 		KEEP AS NON CORE
Summary: plasma membrane is supported during LAMP1 cycling and cytotoxic granule exocytosis, but it is secondary to the lysosomal membrane location.
Reason: Retain as non-core surface/exocytic localization rather than the defining LAMP1 location.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-6800426 		KEEP AS NON CORE
Summary: plasma membrane is supported during LAMP1 cycling and cytotoxic granule exocytosis, but it is secondary to the lysosomal membrane location.
Reason: Retain as non-core surface/exocytic localization rather than the defining LAMP1 location.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0035577 azurophil granule membrane
TAS
Reactome:R-HSA-6798739 		KEEP AS NON CORE
Summary: azurophil granule membrane is a supported lysosome-related secretory granule membrane context in immune cells.
Reason: Retain as cell-type-specific non-core localization.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0101003 ficolin-1-rich granule membrane
TAS
Reactome:R-HSA-6800426 		KEEP AS NON CORE
Summary: ficolin-1-rich granule membrane is a supported lysosome-related secretory granule membrane context in immune cells.
Reason: Retain as cell-type-specific non-core localization.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0048471 perinuclear region of cytoplasm
IMP
PMID:18787122
The Salmonella virulence protein SifA is a G protein antagon... 		KEEP AS NON CORE
Summary: perinuclear region of cytoplasm is a plausible trafficking or lysosome-related context for LAMP1 but is not the defining location or function.
Reason: Retain as non-core context while prioritizing lysosomal/late endosomal membrane annotations.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0005765 lysosomal membrane
ISS
GO_REF:0000024 		ACCEPT
Summary: LAMP1 is a canonical single-pass lysosomal membrane glycoprotein; this is the primary cellular location for its core lysosomal functions.
Reason: Retain as a core location for LAMP1, including the TMEM175-dependent lysosomal pH function.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0010008 endosome membrane
ISS
GO_REF:0000024 		ACCEPT
Summary: LAMP1 shuttles through the endolysosomal system and is supported at the endosome membrane.
Reason: Retain as a core endolysosomal membrane location closely related to the lysosomal membrane role.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0005886 plasma membrane
IDA
PMID:20956541
Syntaxin 4 is required for acid sphingomyelinase activity an... 		KEEP AS NON CORE
Summary: plasma membrane is supported during LAMP1 cycling and cytotoxic granule exocytosis, but it is secondary to the lysosomal membrane location.
Reason: Retain as non-core surface/exocytic localization rather than the defining LAMP1 location.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0005770 late endosome
IDA
PMID:18767904
Hrs and SNX3 functions in sorting and membrane invagination ... 		MODIFY
Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane.
Reason: Use late endosome membrane to capture the integral membrane localization.
Proposed replacements: late endosome membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0070062 extracellular exosome
HDA
PMID:23533145
In-depth proteomic analyses of exosomes isolated from expres... 		KEEP AS NON CORE
Summary: extracellular exosome is a plausible trafficking or lysosome-related context for LAMP1 but is not the defining location or function.
Reason: Retain as non-core context while prioritizing lysosomal/late endosomal membrane annotations.
Supporting Evidence:
PMID:23533145
exosomes isolated from expressed prostatic secretions in urine
GO:0016020 membrane
HDA
PMID:19946888
Defining the membrane proteome of NK cells. 		MODIFY
Summary: membrane is true but too general for LAMP1.
Reason: Replace the broad membrane/vesicle term with lysosomal membrane, the informative core location.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0005764 lysosome
IDA
PMID:23704327
The giant spectrin ÎēV couples the molecular motors to photot... 		MODIFY
Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein.
Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0043323 positive regulation of natural killer cell degranulation
IMP
PMID:23632890
LAMP1/CD107a is required for efficient perforin delivery to ... 		KEEP AS NON CORE
Summary: positive regulation of natural killer cell degranulation is supported in NK-cell cytotoxicity assays but is cell-type-specific.
Reason: Retain as non-core immune-cell biology rather than the general LAMP1 core function.
Supporting Evidence:
PMID:23632890
LAMP1 silencing causes inhibition of NK-cell cytotoxicity
PMID:23632890
Reduction of LAMP1 expression affects the movement of lytic granules
GO:0045954 positive regulation of natural killer cell mediated cytotoxicity
IMP
PMID:23632890
LAMP1/CD107a is required for efficient perforin delivery to ... 		KEEP AS NON CORE
Summary: positive regulation of natural killer cell mediated cytotoxicity is supported in NK-cell cytotoxicity assays but is cell-type-specific.
Reason: Retain as non-core immune-cell biology rather than the general LAMP1 core function.
Supporting Evidence:
PMID:23632890
LAMP1 silencing causes inhibition of NK-cell cytotoxicity
PMID:23632890
Reduction of LAMP1 expression affects the movement of lytic granules
GO:0072594 establishment of protein localization to organelle
IMP
PMID:23632890
LAMP1/CD107a is required for efficient perforin delivery to ... 		KEEP AS NON CORE
Summary: Keep this broad protein-localization process as a non-core NK-cell lytic-granule context.
Reason: PMID:23632890 supports LAMP1-dependent perforin delivery to lytic granules and lytic-granule movement, but not the more specific Golgi-to-lysosome transport term.
Supporting Evidence:
PMID:23632890
LAMP1 silencing causes inhibition of NK-cell cytotoxicity
PMID:23632890
Reduction of LAMP1 expression affects the movement of lytic granules
PMID:23632890
perforin trafficking to lytic granules
GO:0090160 Golgi to lysosome transport
IMP
PMID:23632890
LAMP1/CD107a is required for efficient perforin delivery to ... 		MARK AS OVER ANNOTATED
Summary: Golgi to lysosome transport is too specific for the accessible LAMP1 NK-cell evidence.
Reason: The paper supports perforin delivery and lytic-granule movement, including retention outside lysosomal compartments in TGN-derived vesicles after LAMP1 silencing, but it does not show LAMP1 directly mediates Golgi-to-lysosome transport as a core function.
Supporting Evidence:
PMID:23632890
LAMP1 silencing causes inhibition of NK-cell cytotoxicity
PMID:23632890
Reduction of LAMP1 expression affects the movement of lytic granules
PMID:23632890
more perforin is retained outside of lysosomal compartments in trans-Golgi network-derived transport vesicles
GO:0019899 enzyme binding
IPI
PMID:22641697
The lysosomal polypeptide transporter TAPL is stabilized by ... 		MODIFY
Summary: ABCB9/TAPL binding is real, but the informative effect is stabilization of the lysosomal transporter rather than generic enzyme binding.
Reason: Replace enzyme binding with protein stabilization for the LAMP1/TAPL context.
Proposed replacements: protein stabilization
Supporting Evidence:
PMID:22641697
LAMP proteins retain TAPL on the limiting membrane of endosomes
PMID:22641697
In LAMP-deficient cells, the half-life of TAPL is decreased
GO:0050821 protein stabilization
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: LAMP1/LAMP2 stabilize TAPL/ABCB9 at the endosomal limiting membrane.
Reason: Retain as a supported secondary process rather than the core lysosomal pH function.
Supporting Evidence:
PMID:22641697
LAMP proteins retain TAPL on the limiting membrane of endosomes
PMID:22641697
In LAMP-deficient cells, the half-life of TAPL is decreased
GO:0070062 extracellular exosome
HDA
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exos... 		KEEP AS NON CORE
Summary: extracellular exosome is a plausible trafficking or lysosome-related context for LAMP1 but is not the defining location or function.
Reason: Retain as non-core context while prioritizing lysosomal/late endosomal membrane annotations.
Supporting Evidence:
PMID:19056867
proteomics and phosphoproteomics of urinary exosomes
GO:0005737 cytoplasm
IDA
PMID:21266579
Raftlin is involved in the nucleocapture complex to induce p... 		REMOVE
Summary: cytoplasm is not an appropriate whole-protein location for a single-pass lysosomal membrane glycoprotein.
Reason: A cytosolic tail faces the cytosol, but the protein itself should be annotated to membranes rather than cytosol/cytoplasm.
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Single-pass type I membrane protein
GO:0005764 lysosome
IDA
PMID:22792322
The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62,... 		MODIFY
Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein.
Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0005770 late endosome
IDA
PMID:18388320
Dynamic regulation of ubiquitylation and deubiquitylation at... 		MODIFY
Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane.
Reason: Use late endosome membrane to capture the integral membrane localization.
Proposed replacements: late endosome membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0005764 lysosome
IDA
PMID:15613468
Novel function for receptor activity-modifying proteins (RAM... 		MODIFY
Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein.
Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0005770 late endosome
IDA
PMID:15052268
Mutations in VPS33B, encoding a regulator of SNARE-dependent... 		MODIFY
Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane.
Reason: Use late endosome membrane to capture the integral membrane localization.
Proposed replacements: late endosome membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0005770 late endosome
IDA
PMID:15792797
Regulation of divalent metal transporter expression in human... 		MODIFY
Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane.
Reason: Use late endosome membrane to capture the integral membrane localization.
Proposed replacements: late endosome membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0005764 lysosome
IDA
PMID:15052268
Mutations in VPS33B, encoding a regulator of SNARE-dependent... 		MODIFY
Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein.
Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0005764 lysosome
IDA
PMID:16542649
Palmitoyl protein thioesterase 1 (PPT1) deficiency causes en... 		MODIFY
Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein.
Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0005770 late endosome
IDA
PMID:16542649
Palmitoyl protein thioesterase 1 (PPT1) deficiency causes en... 		MODIFY
Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane.
Reason: Use late endosome membrane to capture the integral membrane localization.
Proposed replacements: late endosome membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0005764 lysosome
IDA
PMID:15292400
Alfy, a novel FYVE-domain-containing protein associated with... 		MODIFY
Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein.
Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0005770 late endosome
IDA
PMID:15292400
Alfy, a novel FYVE-domain-containing protein associated with... 		MODIFY
Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane.
Reason: Use late endosome membrane to capture the integral membrane localization.
Proposed replacements: late endosome membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane; Endosome membrane; Late endosome membrane
PMID:16176980
localizes to late endosomes (LEs)/lysosomes
GO:0005764 lysosome
TAS
PMID:3131762
Molecular cloning of cDNAs encoding lamp A, a human lysosoma... 		MODIFY
Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein.
Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins
GO:0005886 plasma membrane
TAS
PMID:3174652
Derived protein sequence, oligosaccharides, and membrane ins... 		KEEP AS NON CORE
Summary: plasma membrane is supported during LAMP1 cycling and cytotoxic granule exocytosis, but it is secondary to the lysosomal membrane location.
Reason: Retain as non-core surface/exocytic localization rather than the defining LAMP1 location.
Supporting Evidence:
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage
file:human/LAMP1/LAMP1-uniprot.txt
Cell membrane; Cytolytic granule membrane
GO:0016020 membrane
TAS
PMID:3174652
Derived protein sequence, oligosaccharides, and membrane ins... 		MODIFY
Summary: membrane is true but too general for LAMP1.
Reason: Replace the broad membrane/vesicle term with lysosomal membrane, the informative core location.
Proposed replacements: lysosomal membrane
Supporting Evidence:
file:human/LAMP1/LAMP1-uniprot.txt
Lysosome membrane
PMID:17897319
Integral and associated lysosomal membrane proteins

Core Functions

Direct inhibition of the lysosomal TMEM175 cation/proton channel to limit proton leak and support acidic lysosomal lumen pH.

Molecular Function:
ion channel inhibitor activity
Directly Involved In:
lysosomal lumen acidification
Cellular Locations:
lysosomal membrane
Supporting Evidence:
  • PMID:37390818
    directly interact with and inhibit the activity of the lysosomal cation channel TMEM175
  • PMID:37390818
    facilitates lysosomal acidification to a lower pH environment
  • file:human/LAMP1/LAMP1-uniprot.txt
    Acts as a direct inhibitor of the proton channel TMEM175

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000108
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
PMID:15052268
Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome.
PMID:15292400
Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes.
PMID:15613468
Novel function for receptor activity-modifying proteins (RAMPs) in post-endocytic receptor trafficking.
PMID:15792797
Regulation of divalent metal transporter expression in human intestinal epithelial cells following exposure to non-haem iron.
PMID:16176980
The oxysterol-binding protein homologue ORP1L interacts with Rab7 and alters functional properties of late endocytic compartments.
PMID:16542649
Palmitoyl protein thioesterase 1 (PPT1) deficiency causes endocytic defects connected to abnormal saposin processing.
PMID:17897319
Integral and associated lysosomal membrane proteins.
PMID:18388320
Dynamic regulation of ubiquitylation and deubiquitylation at the central spindle during cytokinesis.
PMID:18767904
Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies.
PMID:18787122
The Salmonella virulence protein SifA is a G protein antagonist.
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exosomes.
PMID:19946888
Defining the membrane proteome of NK cells.
PMID:2022921
Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes.
PMID:20956541
Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function.
PMID:21194361
The lysosomal polypeptide transporter TAPL: more than a housekeeping factor?
PMID:21266579
Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation.
PMID:22641697
The lysosomal polypeptide transporter TAPL is stabilized by interaction with LAMP-1 and LAMP-2.
PMID:22792322
The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome.
PMID:23394946
mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state.
PMID:23533145
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
PMID:23632890
LAMP1/CD107a is required for efficient perforin delivery to lytic granules and NK-cell cytotoxicity.
PMID:23704327
The giant spectrin ÎēV couples the molecular motors to phototransduction and Usher syndrome type I proteins along their trafficking route.
PMID:23847195
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage.
PMID:24088571
Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell-mediated cytotoxicity.
PMID:24970085
Virus entry. Lassa virus entry requires a trigger-induced receptor switch.
PMID:25365221
Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation.
PMID:3131762
Molecular cloning of cDNAs encoding lamp A, a human lysosomal membrane glycoprotein with apparent Mr approximately equal to 120,000.
PMID:3174652
Derived protein sequence, oligosaccharides, and membrane insertion of the 120-kDa lysosomal membrane glycoprotein (lgp120): identification of a highly conserved family of lysosomal membrane glycoproteins.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:37390818
Lysosomal LAMP proteins regulate lysosomal pH by direct inhibition of the TMEM175 channel.
PMID:39284914
ER-phagy restrains inflammatory responses through its receptor UBAC2.
Reactome:R-HSA-6798739
Exocytosis of azurophil granule membrane proteins
Reactome:R-HSA-6800426
Exocytosis of ficolin-rich granule membrane proteins
PMID:22885770
Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation.
file:human/LAMP1/LAMP1-uniprot.txt
UniProt record for human LAMP1
file:human/LAMP1/LAMP1-notes.md
LAMP1 curation notes
file:projects/PROTEOSTASIS/mappings/autophagy_lysosome_pathway.yaml
Proteostasis Network autophagy-lysosome pathway mappings

Suggested Questions for Experts

Q: Does the LAMP1-specific clathrin recruitment evidence in ALR warrant a direct lysosome organization or future autophagic lysosome reformation annotation?

Suggested experts: Li Yu, Yongliang Rong

Q: Should GO add a proton-channel-specific child term under ion channel inhibitor activity for LAMP1-TMEM175 regulation?

Suggested experts: Youxing Jiang, GO molecular function editors

Q: How much of the lysosomal pH phenotype is LAMP1-specific versus redundant with LAMP2 in different human cell types?

Suggested experts: Youxing Jiang, Paul Saftig

Suggested Experiments

Experiment: Rescue LAMP1/LAMP2-deficient cells with LAMP1 mutants that disrupt TMEM175 binding while measuring lysosomal pH, TMEM175 currents, and hydrolase activity.

Hypothesis: The LAMP1-TMEM175 interaction is required for LAMP1-dependent lysosomal acidification.

Type: genetic rescue/electrophysiology/lysosomal pH imaging

Experiment: Test LAMP1 cytosolic-tail or glycan mutants during starvation-refeeding ALR and quantify clathrin recruitment, autolysosome tubulation, and proto-lysosome budding.

Hypothesis: A LAMP1-dependent membrane cue recruits or stabilizes clathrin machinery during ALR morphology remodeling.

Type: live-cell imaging/rescue mutagenesis

Experiment: Separate perforin trafficking from lytic granule exocytosis in LAMP1-depleted NK cells using perforin localization, granule motility, degranulation, and target-cell killing assays.

Hypothesis: LAMP1 supports NK cytotoxicity primarily through perforin delivery and lytic granule movement rather than a general degranulation mechanism.

Type: NK-cell RNAi/rescue microscopy/cytotoxicity assay

📚 Additional Documentation

Notes

(LAMP1-notes.md)

LAMP1 review notes

Core function

LAMP1 encodes a heavily glycosylated type I lysosomal membrane glycoprotein.
UniProt describes the protein as a lysosome, endosome, late endosome, cell
membrane, and cytolytic granule membrane protein that shuttles through the
endolysosomal/secretory-lysosome system [file:human/LAMP1/LAMP1-uniprot.txt].
The most informative current molecular function is regulation of lysosomal pH:
LAMP1 and LAMP2 directly interact with TMEM175 and inhibit TMEM175 cation/proton
channel activity, which facilitates lysosomal acidification and hydrolase
activity PMID:37390818.

The core GO interpretation should therefore keep GO:0005765 lysosomal membrane
as the primary location, accept GO:0007042 lysosomal lumen acidification, and
accept GO:0008200 ion channel inhibitor activity as the best available broad
MF term for the TMEM175 inhibition mechanism. The local GO cache does not contain
a more specific proton-channel or TMEM175-channel inhibitor term.

Proteostasis network context

The Proteostasis Network places LAMP1 under
Autophagy-Lysosome Pathway|Autophagic lysosome reformation|Regulation of autolysosome morphology.
The node is marked no_mapping, so PN membership alone is not evidence for a GO
annotation. The workbook note says LAMP1 recruits clathrin to tubules during ALR,
but the locally cached Rong et al. ALR abstract supports clathrin and PI(4,5)P2
as central ALR components without providing a LAMP1-specific statement
PMID:22885770.
I am therefore not adding a new ALR/lysosome-organization annotation from the PN
row alone. Expert follow-up should ask whether the LAMP1-specific clathrin
recruitment evidence is in figures or supplemental material that should support
a future annotation.

Secondary functions and contexts

LAMP1 has a non-core but well-supported role in cytotoxic lymphocyte secretory
lysosomes. LAMP1 RNAi in NK cells reduces cytotoxicity, disturbs lytic-granule
movement, and reduces perforin delivery to lytic granules PMID:23632890. Surface LAMP1 also
protects NK cells from degranulation-associated self-damage by reducing perforin
binding PMID:23847195.
These support NK-cell and cytolytic-granule annotations, but they are not the
general core function of LAMP1.

LAMP1 also stabilizes the lysosomal polypeptide transporter TAPL/ABCB9. The TAPL
paper reports LAMP1/LAMP2 as abundant TAPL interactors and shows that TAPL
half-life is reduced in LAMP-deficient cells PMID:22641697.
This supports protein stabilization as a secondary process, while generic
enzyme/protein-binding annotations are not informative.

LAMP1 is a host factor/receptor for Lassa virus entry in acidic endolysosomal
compartments; this is a valid host-pathogen context but not a normal human core
function PMID:24970085.

Annotation decisions

  • Accept lysosomal membrane, endosome membrane, and late endosome membrane as the
    core membrane locations; modify broader lysosome/endosome/membrane terms to
    those more specific membrane terms.
  • Keep plasma membrane, cell surface, cytolytic granule membrane, azurophil
    granule membrane, ficolin-1-rich granule membrane, extracellular exosome, and
    other trafficking/localization terms as non-core contexts.
  • Remove cytosol/cytoplasm annotations because LAMP1 is an integral membrane
    protein; the cytosolic tail does not justify annotating the whole protein to
    cytosol.
  • Accept lysosomal lumen acidification and ion channel inhibitor activity as core
    TMEM175-dependent functions.
  • Modify broad protein binding to more informative terms where possible:
    TMEM175 binding to ion channel inhibitor activity, Lassa virus binding to virus
    receptor activity, and ABCB9/TAPL binding to protein stabilization.
  • Keep NK-cell degranulation/cytotoxicity and perforin transport terms as
    non-core, cell-type-specific functions.

Deep research provenance

Falcon deep research was started with just deep-research-falcon human LAMP1.
The provider timed out after 600 seconds and no LAMP1-deep-research-falcon.md
file was generated in the gene folder. This review therefore relies on cached
GOA/UniProt, cached publications, PN mappings, and these notes.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

  • Moved out of the YAML description: existing GOA correctly captures lysosomal membrane, late endosome membrane, lysosomal lumen acidification, and broad ion channel inhibitor activity; broad lysosome, endosome, membrane, and generic binding annotations should be narrowed; NK-cell cytotoxicity, TAPL/ABCB9 stabilization, Lassa virus receptor activity, plasma membrane exposure, and lysosome-related granule locations are secondary contexts. The Proteostasis Network ALR morphology row is useful search context but does not by itself justify a new ALR annotation for LAMP1.

Pn Notes

(LAMP1-pn-notes.md)

LAMP1 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: P11279
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-pr-1217 (PR 1217)
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: LAMP1 encodes lysosome-associated membrane glycoprotein 1, an abundant heavily glycosylated single-pass membrane protein of lysosomes, late endosomes, and lysosome-related secretory granules. Its most informative current molecular function is direct inhibition of the lysosomal TMEM175 cation/proton channel, supporting lysosomal lumen acidification and hydrolase activity. LAMP1 also participates in lysosome-related immune granule contexts, TAPL/ABCB9 stabilization, Lassa virus receptor activity, and plasma membrane exposure during degranulation, but its core biology is centered on lysosomal and late-endosomal membrane function.
  • Existing/core annotation action counts: ACCEPT: 15; KEEP_AS_NON_CORE: 35; MARK_AS_OVER_ANNOTATED: 7; MODIFY: 25; REMOVE: 2

PN Consistency Summary

  • Consistency: Consistent. PN note ("LAMP1 recruits clathrin to tubules during ALR") is acknowledged in LAMP1-notes.md, which states the cached Rong et al. ALR abstract (PMID:22885770) supports clathrin/PI(4,5)P2 as ALR components but gives no LAMP1-specific statement. Review therefore does not add an ALR annotation and treats GO:0000421/GO:0044754 (autophagosome/autolysosome) as MARK_AS_OVER_ANNOTATED / KEEP_AS_NON_CORE. No contradiction.
  • PN story / NEW pressure: PN asserts a LAMP1 ALR-morphology role absent from GO, but the node projects nothing and the review correctly judges the evidence insufficient. The review's own NEW pressure is elsewhere: a proposed_new_term "lysosomal proton channel inhibitor activity" (parent GO:0008200) for the TMEM175 mechanism (PMID:37390818). I verified via OLS that no such GO term exists, so this is a defensible new-term candidate, not already captured; the existing GO:0008200 ion channel inhibitor activity is the best current term and is ACCEPTed. Conclusion: ALR over-reaches; TMEM175-inhibitor new term is justified (candidate).
  • Evidence alignment: PN cites one ALR review ("Membrane Trafficking in Autophagy"); review's load-bearing evidence is independent (PMID:37390818 TMEM175, PMID:23632890 NK granules, PMID:22641697 TAPL). Divergence is expected: PN row is search context, not the core LAMP1 function.
  • Verdict: Consistent; PN ALR story correctly not propagated. TMEM175 proton-channel-inhibitor proposed new term is a real GO gap. No edits required.

Full Consistency Review

  • UniProt: P11279 · batch: proteostasis-pr-1217 · review status: COMPLETE
  • PN placement: ALP|Autophagic lysosome reformation|Regulation of autolysosome morphology ; PN-node mapping: group no_mapping; parent class context_only / too_broad_to_propagate / GO:0007040 lysosome organization; branch no_mapping. No projected GO terms.
  • Consistency: Consistent. PN note ("LAMP1 recruits clathrin to tubules during ALR") is acknowledged in LAMP1-notes.md, which states the cached Rong et al. ALR abstract (PMID:22885770) supports clathrin/PI(4,5)P2 as ALR components but gives no LAMP1-specific statement. Review therefore does not add an ALR annotation and treats GO:0000421/GO:0044754 (autophagosome/autolysosome) as MARK_AS_OVER_ANNOTATED / KEEP_AS_NON_CORE. No contradiction.
  • PN story / NEW pressure: PN asserts a LAMP1 ALR-morphology role absent from GO, but the node projects nothing and the review correctly judges the evidence insufficient. The review's own NEW pressure is elsewhere: a proposed_new_term "lysosomal proton channel inhibitor activity" (parent GO:0008200) for the TMEM175 mechanism (PMID:37390818). I verified via OLS that no such GO term exists, so this is a defensible new-term candidate, not already captured; the existing GO:0008200 ion channel inhibitor activity is the best current term and is ACCEPTed. Conclusion: ALR over-reaches; TMEM175-inhibitor new term is justified (candidate).
  • Mapping strategy: No change. no_mapping for the ALR-morphology container is correct (descendants mix components/regulators); the context_only lysosome-organization framing at the class level is right. LAMP1 does not justify upgrading the node to propagation.
  • Evidence alignment: PN cites one ALR review ("Membrane Trafficking in Autophagy"); review's load-bearing evidence is independent (PMID:37390818 TMEM175, PMID:23632890 NK granules, PMID:22641697 TAPL). Divergence is expected: PN row is search context, not the core LAMP1 function.
  • Verdict: Consistent; PN ALR story correctly not propagated. TMEM175 proton-channel-inhibitor proposed new term is a real GO gap. No edits required.

PN Dossier Context

  • review_batch: proteostasis-pr-1217
  • review_yaml: genes/human/LAMP1/LAMP1-ai-review.yaml
  • PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagic lysosome reformation | Regulation of autolysosome morphology

  • UniProt: P11279
  • In branches: ALP
  • Notes: Recruits clathrin to tubules during ALR
  • PN references (titles):
    • Membrane Trafficking in Autophagy - ScienceDirect
  • PN-node mapping records (path + ancestors):
    • [group] Autophagy-Lysosome Pathway|Autophagic lysosome reformation|Regulation of autolysosome morphology
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
    • [class] Autophagy-Lysosome Pathway|Autophagic lysosome reformation
      status=context_only scope=too_broad_to_propagate GO=[GO:0007040 lysosome organization]
      rationale: Autophagic lysosome reformation is the lysosome-regeneration phase that follows autolysosome formation and cargo degradation. As a class, it is better aligned to lysosome organization than to generic autophagy, but the PN members are mechanistically mixed across membrane remodeling, tubulation, product efflux, and unknown late-stage roles, so class-level propagation would still over-annotate.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: P11279
gene_symbol: LAMP1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  LAMP1 encodes lysosome-associated membrane glycoprotein 1, an abundant heavily glycosylated
  single-pass membrane protein of lysosomes, late endosomes, and lysosome-related secretory granules.
  Its most informative current molecular function is direct inhibition of the lysosomal TMEM175
  cation/proton channel, supporting lysosomal lumen acidification and hydrolase activity. LAMP1 also
  participates in lysosome-related immune granule contexts, TAPL/ABCB9 stabilization, Lassa virus
  receptor activity, and plasma membrane exposure during degranulation, but its core biology is
  centered on lysosomal and late-endosomal membrane function.
alternative_products:
- name: '1'
  id: P11279-1
- name: '2'
  id: P11279-2
  sequence_note: VSP_056032
existing_annotations:
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: LAMP1 is a canonical single-pass lysosomal membrane glycoprotein;
      this is the primary cellular location for its core lysosomal functions.
    action: ACCEPT
    reason: Retain as a core location for LAMP1, including the TMEM175-dependent
      lysosomal pH function.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0072594
    label: establishment of protein localization to organelle
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Keep this broad protein-localization process as a non-core NK-cell
      lytic-granule context.
    action: KEEP_AS_NON_CORE
    reason: PMID:23632890 supports LAMP1-dependent perforin delivery to lytic
      granules and lytic-granule movement, but not the more specific
      Golgi-to-lysosome transport term.
    supported_by:
    - reference_id: PMID:23632890
      supporting_text: LAMP1 silencing causes inhibition of NK-cell cytotoxicity
    - reference_id: PMID:23632890
      supporting_text: Reduction of LAMP1 expression affects the movement of
        lytic granules
    - reference_id: PMID:23632890
      supporting_text: perforin trafficking to lytic granules
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: plasma membrane is supported during LAMP1 cycling and cytotoxic
      granule exocytosis, but it is secondary to the lysosomal membrane
      location.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core surface/exocytic localization rather than the
      defining LAMP1 location.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: LAMP1 shuttles through the endolysosomal system and is supported at
      the late endosome membrane.
    action: ACCEPT
    reason: Retain as a core endolysosomal membrane location closely related to
      the lysosomal membrane role.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: LAMP1 is a canonical single-pass lysosomal membrane glycoprotein;
      this is the primary cellular location for its core lysosomal functions.
    action: ACCEPT
    reason: Retain as a core location for LAMP1, including the TMEM175-dependent
      lysosomal pH function.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: located_in
  review:
    summary: cytosol is not an appropriate whole-protein location for a
      single-pass lysosomal membrane glycoprotein.
    action: REMOVE
    reason: A cytosolic tail faces the cytosol, but the protein itself should be
      annotated to membranes rather than cytosol/cytoplasm.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Single-pass type I membrane protein
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: plasma membrane is supported during LAMP1 cycling and cytotoxic
      granule exocytosis, but it is secondary to the lysosomal membrane
      location.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core surface/exocytic localization rather than the
      defining LAMP1 location.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0007042
    label: lysosomal lumen acidification
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: LAMP1 supports lysosomal lumen acidification by inhibiting the
      TMEM175 lysosomal cation/proton channel.
    action: ACCEPT
    reason: Retain as a core process supported by direct LAMP-TMEM175 functional
      evidence.
    supported_by:
    - reference_id: PMID:37390818
      supporting_text: directly interact with and inhibit the activity of the
        lysosomal cation channel TMEM175
    - reference_id: PMID:37390818
      supporting_text: facilitates lysosomal acidification to a lower pH
        environment
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Acts as a direct inhibitor of the proton channel TMEM175
- term:
    id: GO:0008200
    label: ion channel inhibitor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: LAMP1 directly inhibits TMEM175 channel activity; GO currently
      represents this as broad ion channel inhibitor activity.
    action: ACCEPT
    reason: Retain as the best available molecular-function term for the TMEM175
      inhibition mechanism.
    supported_by:
    - reference_id: PMID:37390818
      supporting_text: directly interact with and inhibit the activity of the
        lysosomal cation channel TMEM175
    - reference_id: PMID:37390818
      supporting_text: facilitates lysosomal acidification to a lower pH
        environment
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Acts as a direct inhibitor of the proton channel TMEM175
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: LAMP1 shuttles through the endolysosomal system and is supported at
      the endosome membrane.
    action: ACCEPT
    reason: Retain as a core endolysosomal membrane location closely related to
      the lysosomal membrane role.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: membrane is true but too general for LAMP1.
    action: MODIFY
    reason: Replace the broad membrane/vesicle term with lysosomal membrane, the
      informative core location.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: LAMP1 shuttles through the endolysosomal system and is supported at
      the late endosome membrane.
    action: ACCEPT
    reason: Retain as a core endolysosomal membrane location closely related to
      the lysosomal membrane role.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0035577
    label: azurophil granule membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: azurophil granule membrane is a supported lysosome-related
      secretory granule membrane context in immune cells.
    action: KEEP_AS_NON_CORE
    reason: Retain as cell-type-specific non-core localization.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0101003
    label: ficolin-1-rich granule membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: ficolin-1-rich granule membrane is a supported lysosome-related
      secretory granule membrane context in immune cells.
    action: KEEP_AS_NON_CORE
    reason: Retain as cell-type-specific non-core localization.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0101004
    label: cytolytic granule membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: cytolytic granule membrane is a supported lysosome-related
      secretory granule membrane context in immune cells.
    action: KEEP_AS_NON_CORE
    reason: Retain as cell-type-specific non-core localization.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23394946
  qualifier: enables
  review:
    summary: The reported interaction evidence does not define a useful LAMP1
      molecular function as generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Avoid retaining GO:0005515 when a more specific mechanism is absent
      or captured by another term.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-notes.md
      supporting_text: generic enzyme/protein-binding annotations are not
        informative
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24970085
  qualifier: enables
  review:
    summary: LAMP1 binds Lassa virus glycoprotein in acidic endolysosomal
      compartments, but generic protein binding is not the informative term.
    action: MODIFY
    reason: Use virus receptor activity for this host-pathogen context and keep
      it out of the core LAMP1 function summary.
    proposed_replacement_terms:
    - id: GO:0001618
      label: virus receptor activity
    supported_by:
    - reference_id: PMID:24970085
      supporting_text: involved a pH-dependent switch to an intracellular
        receptor
    - reference_id: PMID:24970085
      supporting_text: The resistance of Lamp1-deficient mice to Lassa virus
        highlights
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: The reported interaction evidence does not define a useful LAMP1
      molecular function as generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Avoid retaining GO:0005515 when a more specific mechanism is absent
      or captured by another term.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-notes.md
      supporting_text: generic enzyme/protein-binding annotations are not
        informative
- term:
    id: GO:0000421
    label: autophagosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Autophagosome membrane is likely an over-extension from
      autophagy/autolysosome contexts; LAMP1 is primarily lysosomal and
      autolysosomal after fusion.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not treat LAMP1 as a canonical autophagosome membrane protein
      without direct gene-specific evidence.
    supported_by:
    - reference_id: PMID:22885770
      supporting_text: clathrin and phosphatidylinositol-4,5-bisphosphate
    - reference_id: file:human/LAMP1/LAMP1-notes.md
      supporting_text: PN membership alone is not evidence for a GO annotation
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Lysosome is correct but less precise than lysosomal membrane for
      this type I membrane glycoprotein.
    action: MODIFY
    reason: Use the more specific lysosomal membrane term for a single-pass
      LAMP-family membrane protein.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Endosome is correct as a broad compartment, but LAMP1 is
      specifically an endosomal membrane protein.
    action: MODIFY
    reason: Use endosome membrane to capture the integral membrane localization.
    proposed_replacement_terms:
    - id: GO:0010008
      label: endosome membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Late endosome is correct as a broad compartment, but LAMP1 is
      specifically on the late endosome membrane.
    action: MODIFY
    reason: Use late endosome membrane to capture the integral membrane
      localization.
    proposed_replacement_terms:
    - id: GO:0031902
      label: late endosome membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0005771
    label: multivesicular body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: multivesicular body is a plausible trafficking or lysosome-related
      context for LAMP1 but is not the defining location or function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core context while prioritizing lysosomal/late
      endosomal membrane annotations.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0008021
    label: synaptic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: synaptic vesicle is a plausible trafficking or lysosome-related
      context for LAMP1 but is not the defining location or function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core context while prioritizing lysosomal/late
      endosomal membrane annotations.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0009897
    label: external side of plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: external side of plasma membrane is supported during LAMP1 cycling
      and cytotoxic granule exocytosis, but it is secondary to the lysosomal
      membrane location.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core surface/exocytic localization rather than the
      defining LAMP1 location.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: cell surface is supported during LAMP1 cycling and cytotoxic
      granule exocytosis, but it is secondary to the lysosomal membrane
      location.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core surface/exocytic localization rather than the
      defining LAMP1 location.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Protein domain specific binding is an uninformative automated
      transfer for LAMP1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not retain broad binding terms without a specific functional
      mechanism.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-notes.md
      supporting_text: Generic enzyme/protein-binding annotations are not
        informative
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: vesicle is true but too general for LAMP1.
    action: MODIFY
    reason: Replace the broad membrane/vesicle term with lysosomal membrane, the
      informative core location.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0042383
    label: sarcolemma
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: sarcolemma is a plausible trafficking or lysosome-related context
      for LAMP1 but is not the defining location or function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core context while prioritizing lysosomal/late
      endosomal membrane annotations.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0042470
    label: melanosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: melanosome is a plausible trafficking or lysosome-related context
      for LAMP1 but is not the defining location or function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core context while prioritizing lysosomal/late
      endosomal membrane annotations.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0044194
    label: cytolytic granule
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Cytolytic granule is a supported secretory-lysosome context, but
      LAMP1 is a membrane protein.
    action: MODIFY
    reason: Use cytolytic granule membrane for the more precise compartment.
    proposed_replacement_terms:
    - id: GO:0101004
      label: cytolytic granule membrane
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0044754
    label: autolysosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: autolysosome is a plausible trafficking or lysosome-related context
      for LAMP1 but is not the defining location or function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core context while prioritizing lysosomal/late
      endosomal membrane annotations.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0045335
    label: phagocytic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: phagocytic vesicle is a plausible trafficking or lysosome-related
      context for LAMP1 but is not the defining location or function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core context while prioritizing lysosomal/late
      endosomal membrane annotations.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: LAMP1/LAMP2 stabilize TAPL/ABCB9 at the endosomal limiting
      membrane.
    action: KEEP_AS_NON_CORE
    reason: Retain as a supported secondary process rather than the core
      lysosomal pH function.
    supported_by:
    - reference_id: PMID:22641697
      supporting_text: LAMP proteins retain TAPL on the limiting membrane of
        endosomes
    - reference_id: PMID:22641697
      supporting_text: In LAMP-deficient cells, the half-life of TAPL is
        decreased
- term:
    id: GO:0061474
    label: phagolysosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: phagolysosome membrane is a plausible trafficking or
      lysosome-related context for LAMP1 but is not the defining location or
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core context while prioritizing lysosomal/late
      endosomal membrane annotations.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:39284914
  qualifier: enables
  review:
    summary: The ER-phagy paper uses LAMP1-positive compartments and reports
      UBAC2 association with LAMP1, but LAMP1 is not the mechanistic receptor in
      that study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding would overstate LAMP1 function; the study is
      mainly about UBAC2/GABARAP-mediated ER-phagy.
    supported_by:
    - reference_id: PMID:39284914
      supporting_text: autophagy activation promoted the distribution of UBAC2
        into LAMP1
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: EXP
  original_reference_id: PMID:17897319
  qualifier: located_in
  review:
    summary: LAMP1 is a canonical single-pass lysosomal membrane glycoprotein;
      this is the primary cellular location for its core lysosomal functions.
    action: ACCEPT
    reason: Retain as a core location for LAMP1, including the TMEM175-dependent
      lysosomal pH function.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: EXP
  original_reference_id: PMID:2022921
  qualifier: located_in
  review:
    summary: plasma membrane is supported during LAMP1 cycling and cytotoxic
      granule exocytosis, but it is secondary to the lysosomal membrane
      location.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core surface/exocytic localization rather than the
      defining LAMP1 location.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: EXP
  original_reference_id: PMID:23847195
  qualifier: located_in
  review:
    summary: plasma membrane is supported during LAMP1 cycling and cytotoxic
      granule exocytosis, but it is secondary to the lysosomal membrane
      location.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core surface/exocytic localization rather than the
      defining LAMP1 location.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: EXP
  original_reference_id: PMID:16176980
  qualifier: located_in
  review:
    summary: LAMP1 shuttles through the endolysosomal system and is supported at
      the endosome membrane.
    action: ACCEPT
    reason: Retain as a core endolysosomal membrane location closely related to
      the lysosomal membrane role.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: EXP
  original_reference_id: PMID:16176980
  qualifier: located_in
  review:
    summary: LAMP1 shuttles through the endolysosomal system and is supported at
      the late endosome membrane.
    action: ACCEPT
    reason: Retain as a core endolysosomal membrane location closely related to
      the lysosomal membrane role.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0101004
    label: cytolytic granule membrane
  evidence_type: EXP
  original_reference_id: PMID:2022921
  qualifier: located_in
  review:
    summary: cytolytic granule membrane is a supported lysosome-related
      secretory granule membrane context in immune cells.
    action: KEEP_AS_NON_CORE
    reason: Retain as cell-type-specific non-core localization.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37390818
  qualifier: enables
  review:
    summary: The TMEM175 interaction is real, but generic protein binding hides
      the informative channel-inhibitor mechanism.
    action: MODIFY
    reason: Replace with ion channel inhibitor activity for the LAMP1-TMEM175
      functional interaction.
    proposed_replacement_terms:
    - id: GO:0008200
      label: ion channel inhibitor activity
    supported_by:
    - reference_id: PMID:37390818
      supporting_text: directly interact with and inhibit the activity of the
        lysosomal cation channel TMEM175
    - reference_id: PMID:37390818
      supporting_text: facilitates lysosomal acidification to a lower pH
        environment
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Acts as a direct inhibitor of the proton channel TMEM175
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IDA
  original_reference_id: PMID:16176980
  qualifier: is_active_in
  review:
    summary: LAMP1 is a canonical single-pass lysosomal membrane glycoprotein;
      this is the primary cellular location for its core lysosomal functions.
    action: ACCEPT
    reason: Retain as a core location for LAMP1, including the TMEM175-dependent
      lysosomal pH function.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0007042
    label: lysosomal lumen acidification
  evidence_type: IDA
  original_reference_id: PMID:37390818
  qualifier: involved_in
  review:
    summary: LAMP1 supports lysosomal lumen acidification by inhibiting the
      TMEM175 lysosomal cation/proton channel.
    action: ACCEPT
    reason: Retain as a core process supported by direct LAMP-TMEM175 functional
      evidence.
    supported_by:
    - reference_id: PMID:37390818
      supporting_text: directly interact with and inhibit the activity of the
        lysosomal cation channel TMEM175
    - reference_id: PMID:37390818
      supporting_text: facilitates lysosomal acidification to a lower pH
        environment
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Acts as a direct inhibitor of the proton channel TMEM175
- term:
    id: GO:0008200
    label: ion channel inhibitor activity
  evidence_type: IDA
  original_reference_id: PMID:37390818
  qualifier: enables
  review:
    summary: LAMP1 directly inhibits TMEM175 channel activity; GO currently
      represents this as broad ion channel inhibitor activity.
    action: ACCEPT
    reason: Retain as the best available molecular-function term for the TMEM175
      inhibition mechanism.
    supported_by:
    - reference_id: PMID:37390818
      supporting_text: directly interact with and inhibit the activity of the
        lysosomal cation channel TMEM175
    - reference_id: PMID:37390818
      supporting_text: facilitates lysosomal acidification to a lower pH
        environment
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Acts as a direct inhibitor of the proton channel TMEM175
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:25365221
  qualifier: located_in
  review:
    summary: Lysosome is correct but less precise than lysosomal membrane for
      this type I membrane glycoprotein.
    action: MODIFY
    reason: Use the more specific lysosomal membrane term for a single-pass
      LAMP-family membrane protein.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21194361
  qualifier: enables
  review:
    summary: The reported interaction evidence does not define a useful LAMP1
      molecular function as generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Avoid retaining GO:0005515 when a more specific mechanism is absent
      or captured by another term.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-notes.md
      supporting_text: generic enzyme/protein-binding annotations are not
        informative
- term:
    id: GO:0101004
    label: cytolytic granule membrane
  evidence_type: IDA
  original_reference_id: PMID:24088571
  qualifier: located_in
  review:
    summary: cytolytic granule membrane is a supported lysosome-related
      secretory granule membrane context in immune cells.
    action: KEEP_AS_NON_CORE
    reason: Retain as cell-type-specific non-core localization.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0140507
    label: granzyme-mediated programmed cell death signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:23632890
  qualifier: involved_in
  review:
    summary: granzyme-mediated programmed cell death signaling pathway is
      supported in NK-cell cytotoxicity assays but is cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune-cell biology rather than the general LAMP1
      core function.
    supported_by:
    - reference_id: PMID:23632890
      supporting_text: LAMP1 silencing causes inhibition of NK-cell cytotoxicity
    - reference_id: PMID:23632890
      supporting_text: Reduction of LAMP1 expression affects the movement of
        lytic granules
- term:
    id: GO:1902513
    label: regulation of organelle transport along microtubule
  evidence_type: IMP
  original_reference_id: PMID:23632890
  qualifier: involved_in
  review:
    summary: regulation of organelle transport along microtubule is supported in
      NK-cell cytotoxicity assays but is cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune-cell biology rather than the general LAMP1
      core function.
    supported_by:
    - reference_id: PMID:23632890
      supporting_text: LAMP1 silencing causes inhibition of NK-cell cytotoxicity
    - reference_id: PMID:23632890
      supporting_text: Reduction of LAMP1 expression affects the movement of
        lytic granules
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798739
  qualifier: located_in
  review:
    summary: plasma membrane is supported during LAMP1 cycling and cytotoxic
      granule exocytosis, but it is secondary to the lysosomal membrane
      location.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core surface/exocytic localization rather than the
      defining LAMP1 location.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800426
  qualifier: located_in
  review:
    summary: plasma membrane is supported during LAMP1 cycling and cytotoxic
      granule exocytosis, but it is secondary to the lysosomal membrane
      location.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core surface/exocytic localization rather than the
      defining LAMP1 location.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0035577
    label: azurophil granule membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798739
  qualifier: located_in
  review:
    summary: azurophil granule membrane is a supported lysosome-related
      secretory granule membrane context in immune cells.
    action: KEEP_AS_NON_CORE
    reason: Retain as cell-type-specific non-core localization.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0101003
    label: ficolin-1-rich granule membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800426
  qualifier: located_in
  review:
    summary: ficolin-1-rich granule membrane is a supported lysosome-related
      secretory granule membrane context in immune cells.
    action: KEEP_AS_NON_CORE
    reason: Retain as cell-type-specific non-core localization.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IMP
  original_reference_id: PMID:18787122
  qualifier: located_in
  review:
    summary: perinuclear region of cytoplasm is a plausible trafficking or
      lysosome-related context for LAMP1 but is not the defining location or
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core context while prioritizing lysosomal/late
      endosomal membrane annotations.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: LAMP1 is a canonical single-pass lysosomal membrane glycoprotein;
      this is the primary cellular location for its core lysosomal functions.
    action: ACCEPT
    reason: Retain as a core location for LAMP1, including the TMEM175-dependent
      lysosomal pH function.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: LAMP1 shuttles through the endolysosomal system and is supported at
      the endosome membrane.
    action: ACCEPT
    reason: Retain as a core endolysosomal membrane location closely related to
      the lysosomal membrane role.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:20956541
  qualifier: located_in
  review:
    summary: plasma membrane is supported during LAMP1 cycling and cytotoxic
      granule exocytosis, but it is secondary to the lysosomal membrane
      location.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core surface/exocytic localization rather than the
      defining LAMP1 location.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:18767904
  qualifier: located_in
  review:
    summary: Late endosome is correct as a broad compartment, but LAMP1 is
      specifically on the late endosome membrane.
    action: MODIFY
    reason: Use late endosome membrane to capture the integral membrane
      localization.
    proposed_replacement_terms:
    - id: GO:0031902
      label: late endosome membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: extracellular exosome is a plausible trafficking or
      lysosome-related context for LAMP1 but is not the defining location or
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core context while prioritizing lysosomal/late
      endosomal membrane annotations.
    supported_by:
    - reference_id: PMID:23533145
      supporting_text: exosomes isolated from expressed prostatic secretions in
        urine
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: membrane is true but too general for LAMP1.
    action: MODIFY
    reason: Replace the broad membrane/vesicle term with lysosomal membrane, the
      informative core location.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:23704327
  qualifier: located_in
  review:
    summary: Lysosome is correct but less precise than lysosomal membrane for
      this type I membrane glycoprotein.
    action: MODIFY
    reason: Use the more specific lysosomal membrane term for a single-pass
      LAMP-family membrane protein.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0043323
    label: positive regulation of natural killer cell degranulation
  evidence_type: IMP
  original_reference_id: PMID:23632890
  qualifier: involved_in
  review:
    summary: positive regulation of natural killer cell degranulation is
      supported in NK-cell cytotoxicity assays but is cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune-cell biology rather than the general LAMP1
      core function.
    supported_by:
    - reference_id: PMID:23632890
      supporting_text: LAMP1 silencing causes inhibition of NK-cell cytotoxicity
    - reference_id: PMID:23632890
      supporting_text: Reduction of LAMP1 expression affects the movement of
        lytic granules
- term:
    id: GO:0045954
    label: positive regulation of natural killer cell mediated cytotoxicity
  evidence_type: IMP
  original_reference_id: PMID:23632890
  qualifier: involved_in
  review:
    summary: positive regulation of natural killer cell mediated cytotoxicity is
      supported in NK-cell cytotoxicity assays but is cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune-cell biology rather than the general LAMP1
      core function.
    supported_by:
    - reference_id: PMID:23632890
      supporting_text: LAMP1 silencing causes inhibition of NK-cell cytotoxicity
    - reference_id: PMID:23632890
      supporting_text: Reduction of LAMP1 expression affects the movement of
        lytic granules
- term:
    id: GO:0072594
    label: establishment of protein localization to organelle
  evidence_type: IMP
  original_reference_id: PMID:23632890
  qualifier: involved_in
  review:
    summary: Keep this broad protein-localization process as a non-core NK-cell
      lytic-granule context.
    action: KEEP_AS_NON_CORE
    reason: PMID:23632890 supports LAMP1-dependent perforin delivery to lytic
      granules and lytic-granule movement, but not the more specific
      Golgi-to-lysosome transport term.
    supported_by:
    - reference_id: PMID:23632890
      supporting_text: LAMP1 silencing causes inhibition of NK-cell cytotoxicity
    - reference_id: PMID:23632890
      supporting_text: Reduction of LAMP1 expression affects the movement of
        lytic granules
    - reference_id: PMID:23632890
      supporting_text: perforin trafficking to lytic granules
- term:
    id: GO:0090160
    label: Golgi to lysosome transport
  evidence_type: IMP
  original_reference_id: PMID:23632890
  qualifier: involved_in
  review:
    summary: Golgi to lysosome transport is too specific for the accessible LAMP1
      NK-cell evidence.
    action: MARK_AS_OVER_ANNOTATED
    reason: The paper supports perforin delivery and lytic-granule movement,
      including retention outside lysosomal compartments in TGN-derived vesicles
      after LAMP1 silencing, but it does not show LAMP1 directly mediates
      Golgi-to-lysosome transport as a core function.
    proposed_replacement_terms:
    - id: GO:0072594
      label: establishment of protein localization to organelle
    supported_by:
    - reference_id: PMID:23632890
      supporting_text: LAMP1 silencing causes inhibition of NK-cell cytotoxicity
    - reference_id: PMID:23632890
      supporting_text: Reduction of LAMP1 expression affects the movement of
        lytic granules
    - reference_id: PMID:23632890
      supporting_text: more perforin is retained outside of lysosomal compartments in trans-Golgi network-derived transport vesicles
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:22641697
  qualifier: enables
  review:
    summary: ABCB9/TAPL binding is real, but the informative effect is
      stabilization of the lysosomal transporter rather than generic enzyme
      binding.
    action: MODIFY
    reason: Replace enzyme binding with protein stabilization for the LAMP1/TAPL
      context.
    proposed_replacement_terms:
    - id: GO:0050821
      label: protein stabilization
    supported_by:
    - reference_id: PMID:22641697
      supporting_text: LAMP proteins retain TAPL on the limiting membrane of
        endosomes
    - reference_id: PMID:22641697
      supporting_text: In LAMP-deficient cells, the half-life of TAPL is
        decreased
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: LAMP1/LAMP2 stabilize TAPL/ABCB9 at the endosomal limiting
      membrane.
    action: KEEP_AS_NON_CORE
    reason: Retain as a supported secondary process rather than the core
      lysosomal pH function.
    supported_by:
    - reference_id: PMID:22641697
      supporting_text: LAMP proteins retain TAPL on the limiting membrane of
        endosomes
    - reference_id: PMID:22641697
      supporting_text: In LAMP-deficient cells, the half-life of TAPL is
        decreased
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: extracellular exosome is a plausible trafficking or
      lysosome-related context for LAMP1 but is not the defining location or
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core context while prioritizing lysosomal/late
      endosomal membrane annotations.
    supported_by:
    - reference_id: PMID:19056867
      supporting_text: proteomics and phosphoproteomics of urinary exosomes
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:21266579
  qualifier: located_in
  review:
    summary: cytoplasm is not an appropriate whole-protein location for a
      single-pass lysosomal membrane glycoprotein.
    action: REMOVE
    reason: A cytosolic tail faces the cytosol, but the protein itself should be
      annotated to membranes rather than cytosol/cytoplasm.
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Single-pass type I membrane protein
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:22792322
  qualifier: located_in
  review:
    summary: Lysosome is correct but less precise than lysosomal membrane for
      this type I membrane glycoprotein.
    action: MODIFY
    reason: Use the more specific lysosomal membrane term for a single-pass
      LAMP-family membrane protein.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:18388320
  qualifier: located_in
  review:
    summary: Late endosome is correct as a broad compartment, but LAMP1 is
      specifically on the late endosome membrane.
    action: MODIFY
    reason: Use late endosome membrane to capture the integral membrane
      localization.
    proposed_replacement_terms:
    - id: GO:0031902
      label: late endosome membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:15613468
  qualifier: colocalizes_with
  review:
    summary: Lysosome is correct but less precise than lysosomal membrane for
      this type I membrane glycoprotein.
    action: MODIFY
    reason: Use the more specific lysosomal membrane term for a single-pass
      LAMP-family membrane protein.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:15052268
  qualifier: located_in
  review:
    summary: Late endosome is correct as a broad compartment, but LAMP1 is
      specifically on the late endosome membrane.
    action: MODIFY
    reason: Use late endosome membrane to capture the integral membrane
      localization.
    proposed_replacement_terms:
    - id: GO:0031902
      label: late endosome membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:15792797
  qualifier: located_in
  review:
    summary: Late endosome is correct as a broad compartment, but LAMP1 is
      specifically on the late endosome membrane.
    action: MODIFY
    reason: Use late endosome membrane to capture the integral membrane
      localization.
    proposed_replacement_terms:
    - id: GO:0031902
      label: late endosome membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:15052268
  qualifier: located_in
  review:
    summary: Lysosome is correct but less precise than lysosomal membrane for
      this type I membrane glycoprotein.
    action: MODIFY
    reason: Use the more specific lysosomal membrane term for a single-pass
      LAMP-family membrane protein.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:16542649
  qualifier: located_in
  review:
    summary: Lysosome is correct but less precise than lysosomal membrane for
      this type I membrane glycoprotein.
    action: MODIFY
    reason: Use the more specific lysosomal membrane term for a single-pass
      LAMP-family membrane protein.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:16542649
  qualifier: located_in
  review:
    summary: Late endosome is correct as a broad compartment, but LAMP1 is
      specifically on the late endosome membrane.
    action: MODIFY
    reason: Use late endosome membrane to capture the integral membrane
      localization.
    proposed_replacement_terms:
    - id: GO:0031902
      label: late endosome membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:15292400
  qualifier: located_in
  review:
    summary: Lysosome is correct but less precise than lysosomal membrane for
      this type I membrane glycoprotein.
    action: MODIFY
    reason: Use the more specific lysosomal membrane term for a single-pass
      LAMP-family membrane protein.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:15292400
  qualifier: located_in
  review:
    summary: Late endosome is correct as a broad compartment, but LAMP1 is
      specifically on the late endosome membrane.
    action: MODIFY
    reason: Use late endosome membrane to capture the integral membrane
      localization.
    proposed_replacement_terms:
    - id: GO:0031902
      label: late endosome membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane; Endosome membrane; Late endosome
        membrane
    - reference_id: PMID:16176980
      supporting_text: localizes to late endosomes (LEs)/lysosomes
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: TAS
  original_reference_id: PMID:3131762
  qualifier: located_in
  review:
    summary: Lysosome is correct but less precise than lysosomal membrane for
      this type I membrane glycoprotein.
    action: MODIFY
    reason: Use the more specific lysosomal membrane term for a single-pass
      LAMP-family membrane protein.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: PMID:3174652
  qualifier: located_in
  review:
    summary: plasma membrane is supported during LAMP1 cycling and cytotoxic
      granule exocytosis, but it is secondary to the lysosomal membrane
      location.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core surface/exocytic localization rather than the
      defining LAMP1 location.
    supported_by:
    - reference_id: PMID:23847195
      supporting_text: Surface CD107a/LAMP-1 protects natural killer cells from
        degranulation-associated damage
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Cell membrane; Cytolytic granule membrane
- term:
    id: GO:0016020
    label: membrane
  evidence_type: TAS
  original_reference_id: PMID:3174652
  qualifier: located_in
  review:
    summary: membrane is true but too general for LAMP1.
    action: MODIFY
    reason: Replace the broad membrane/vesicle term with lysosomal membrane, the
      informative core location.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:17897319
      supporting_text: Integral and associated lysosomal membrane proteins
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with
    GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular
    Location vocabulary mapping, accompanied by conservative changes to GO terms
    applied by UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data
    to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on
    inter-ontology links
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning
    models
  findings: []
- id: PMID:15052268
  title: Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane
    fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome.
  findings: []
- id: PMID:15292400
  title: Alfy, a novel FYVE-domain-containing protein associated with protein
    granules and autophagic membranes.
  findings: []
- id: PMID:15613468
  title: Novel function for receptor activity-modifying proteins (RAMPs) in
    post-endocytic receptor trafficking.
  findings: []
- id: PMID:15792797
  title: Regulation of divalent metal transporter expression in human intestinal
    epithelial cells following exposure to non-haem iron.
  findings: []
- id: PMID:16176980
  title: The oxysterol-binding protein homologue ORP1L interacts with Rab7 and
    alters functional properties of late endocytic compartments.
  findings: []
- id: PMID:16542649
  title: Palmitoyl protein thioesterase 1 (PPT1) deficiency causes endocytic
    defects connected to abnormal saposin processing.
  findings: []
- id: PMID:17897319
  title: Integral and associated lysosomal membrane proteins.
  findings: []
- id: PMID:18388320
  title: Dynamic regulation of ubiquitylation and deubiquitylation at the
    central spindle during cytokinesis.
  findings: []
- id: PMID:18767904
  title: Hrs and SNX3 functions in sorting and membrane invagination within
    multivesicular bodies.
  findings: []
- id: PMID:18787122
  title: The Salmonella virulence protein SifA is a G protein antagonist.
  findings: []
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:2022921
  title: Cytotoxic T lymphocyte granules are secretory lysosomes, containing
    both perforin and granzymes.
  findings: []
- id: PMID:20956541
  title: Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic
    function.
  findings: []
- id: PMID:21194361
  title: 'The lysosomal polypeptide transporter TAPL: more than a housekeeping factor?'
  findings: []
- id: PMID:21266579
  title: Raftlin is involved in the nucleocapture complex to induce
    poly(I:C)-mediated TLR3 activation.
  findings: []
- id: PMID:22641697
  title: The lysosomal polypeptide transporter TAPL is stabilized by interaction
    with LAMP-1 and LAMP-2.
  findings: []
- id: PMID:22792322
  title: The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and
    promotes the sequestration and clearance of ubiquitinated proteins into the
    aggresome.
  findings: []
- id: PMID:23394946
  title: mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt
    to metabolic state.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed
    prostatic secretions in urine.
  findings: []
- id: PMID:23632890
  title: LAMP1/CD107a is required for efficient perforin delivery to lytic
    granules and NK-cell cytotoxicity.
  findings: []
- id: PMID:23704327
  title: The giant spectrin ÎēV couples the molecular motors to phototransduction
    and Usher syndrome type I proteins along their trafficking route.
  findings: []
- id: PMID:23847195
  title: Surface CD107a/LAMP-1 protects natural killer cells from
    degranulation-associated damage.
  findings: []
- id: PMID:24088571
  title: Arf-like GTPase Arl8b regulates lytic granule polarization and natural
    killer cell-mediated cytotoxicity.
  findings: []
- id: PMID:24970085
  title: Virus entry. Lassa virus entry requires a trigger-induced receptor
    switch.
  findings: []
- id: PMID:25365221
  title: Spastic paraplegia proteins spastizin and spatacsin mediate autophagic
    lysosome reformation.
  findings: []
- id: PMID:3131762
  title: Molecular cloning of cDNAs encoding lamp A, a human lysosomal membrane
    glycoprotein with apparent Mr approximately equal to 120,000.
  findings: []
- id: PMID:3174652
  title: 'Derived protein sequence, oligosaccharides, and membrane insertion of the
    120-kDa lysosomal membrane glycoprotein (lgp120): identification of a highly conserved
    family of lysosomal membrane glycoproteins.'
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:37390818
  title: Lysosomal LAMP proteins regulate lysosomal pH by direct inhibition of
    the TMEM175 channel.
  findings: []
- id: PMID:39284914
  title: ER-phagy restrains inflammatory responses through its receptor UBAC2.
  findings: []
- id: Reactome:R-HSA-6798739
  title: Exocytosis of azurophil granule membrane proteins
  findings: []
- id: Reactome:R-HSA-6800426
  title: Exocytosis of ficolin-rich granule membrane proteins
  findings: []
- id: PMID:22885770
  title: Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic
    lysosome reformation.
  findings: []
- id: file:human/LAMP1/LAMP1-uniprot.txt
  title: UniProt record for human LAMP1
  findings: []
- id: file:human/LAMP1/LAMP1-notes.md
  title: LAMP1 curation notes
  findings: []
- id: file:projects/PROTEOSTASIS/mappings/autophagy_lysosome_pathway.yaml
  title: Proteostasis Network autophagy-lysosome pathway mappings
  findings: []
core_functions:
- description: Direct inhibition of the lysosomal TMEM175 cation/proton channel
    to limit proton leak and support acidic lysosomal lumen pH.
  molecular_function:
    id: GO:0008200
    label: ion channel inhibitor activity
  directly_involved_in:
  - id: GO:0007042
    label: lysosomal lumen acidification
  locations:
  - id: GO:0005765
    label: lysosomal membrane
  supported_by:
  - reference_id: PMID:37390818
    supporting_text: directly interact with and inhibit the activity of the
      lysosomal cation channel TMEM175
  - reference_id: PMID:37390818
    supporting_text: facilitates lysosomal acidification to a lower pH
      environment
  - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
    supporting_text: Acts as a direct inhibitor of the proton channel TMEM175
proposed_new_terms:
- proposed_name: lysosomal proton channel inhibitor activity
  proposed_definition: An ion channel inhibitor activity that decreases the
    activity of a proton-conducting channel in the lysosomal membrane.
  justification: LAMP1 inhibits TMEM175 proton leak channel activity, but the
    current available GO term is only broad ion channel inhibitor activity.
  proposed_parent:
    id: GO:0008200
    label: ion channel inhibitor activity
  supported_by:
  - reference_id: PMID:37390818
    supporting_text: directly interact with and inhibit the activity of the
      lysosomal cation channel TMEM175
  - reference_id: PMID:37390818
    supporting_text: facilitates lysosomal acidification to a lower pH
      environment
  - reference_id: file:human/LAMP1/LAMP1-uniprot.txt
    supporting_text: Acts as a direct inhibitor of the proton channel TMEM175
suggested_questions:
- question: Does the LAMP1-specific clathrin recruitment evidence in ALR warrant
    a direct lysosome organization or future autophagic lysosome reformation
    annotation?
  experts:
  - Li Yu
  - Yongliang Rong
- question: Should GO add a proton-channel-specific child term under ion channel
    inhibitor activity for LAMP1-TMEM175 regulation?
  experts:
  - Youxing Jiang
  - GO molecular function editors
- question: How much of the lysosomal pH phenotype is LAMP1-specific versus
    redundant with LAMP2 in different human cell types?
  experts:
  - Youxing Jiang
  - Paul Saftig
suggested_experiments:
- description: Rescue LAMP1/LAMP2-deficient cells with LAMP1 mutants that
    disrupt TMEM175 binding while measuring lysosomal pH, TMEM175 currents, and
    hydrolase activity.
  experiment_type: genetic rescue/electrophysiology/lysosomal pH imaging
  hypothesis: The LAMP1-TMEM175 interaction is required for LAMP1-dependent
    lysosomal acidification.
- description: Test LAMP1 cytosolic-tail or glycan mutants during
    starvation-refeeding ALR and quantify clathrin recruitment, autolysosome
    tubulation, and proto-lysosome budding.
  experiment_type: live-cell imaging/rescue mutagenesis
  hypothesis: A LAMP1-dependent membrane cue recruits or stabilizes clathrin
    machinery during ALR morphology remodeling.
- description: Separate perforin trafficking from lytic granule exocytosis in
    LAMP1-depleted NK cells using perforin localization, granule motility,
    degranulation, and target-cell killing assays.
  experiment_type: NK-cell RNAi/rescue microscopy/cytotoxicity assay
  hypothesis: LAMP1 supports NK cytotoxicity primarily through perforin delivery
    and lytic granule movement rather than a general degranulation mechanism.