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.
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:
| 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 Ξ²V 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. Proposed replacements: establishment of protein localization to organelle 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... | TOO GENERAL | Summary: True but broad: entailed by autolysosome, azurophil granule membrane and cytolytic granule membrane and others, kept in this review. Reason: GO's cytoplasm covers everything inside the plasma membrane except the nucleus, organelles and secretory compartments included, so autolysosome, azurophil granule membrane and cytolytic granule membrane and others, kept in this review, entail this term and the claim is true. TOO_GENERAL rather than REMOVE. The objection is a reason not to annotate a narrower term such as cytosol, not to remove this one. Objection recorded at removal: A cytosolic tail faces the cytosol, but the protein itself should be annotated to membranes rather than cytosol/cytoplasm. Summary at removal: cytoplasm is not an appropriate whole-protein location for a single-pass lysosomal membrane glycoprotein. 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 |
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Download this section (compressed HTML)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
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
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