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 βV 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.