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... | REMOVE | Summary: cytoplasm is not an appropriate whole-protein location for a single-pass lysosomal membrane glycoprotein. Reason: A cytosolic tail faces the cytosol, but the protein itself should be annotated to membranes rather than cytosol/cytoplasm. Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Single-pass type I membrane protein |
| GO:0005764 lysosome | IDA PMID:22792322 The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62,... | MODIFY | Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein. Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein. Proposed replacements: lysosomal membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane PMID:17897319 Integral and associated lysosomal membrane proteins |
| GO:0005770 late endosome | IDA PMID:18388320 Dynamic regulation of ubiquitylation and deubiquitylation at... | MODIFY | Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane. Reason: Use late endosome membrane to capture the integral membrane localization. Proposed replacements: late endosome membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane; Endosome membrane; Late endosome membrane PMID:16176980 localizes to late endosomes (LEs)/lysosomes |
| GO:0005764 lysosome | IDA PMID:15613468 Novel function for receptor activity-modifying proteins (RAM... | MODIFY | Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein. Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein. Proposed replacements: lysosomal membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane PMID:17897319 Integral and associated lysosomal membrane proteins |
| GO:0005770 late endosome | IDA PMID:15052268 Mutations in VPS33B, encoding a regulator of SNARE-dependent... | MODIFY | Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane. Reason: Use late endosome membrane to capture the integral membrane localization. Proposed replacements: late endosome membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane; Endosome membrane; Late endosome membrane PMID:16176980 localizes to late endosomes (LEs)/lysosomes |
| GO:0005770 late endosome | IDA PMID:15792797 Regulation of divalent metal transporter expression in human... | MODIFY | Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane. Reason: Use late endosome membrane to capture the integral membrane localization. Proposed replacements: late endosome membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane; Endosome membrane; Late endosome membrane PMID:16176980 localizes to late endosomes (LEs)/lysosomes |
| GO:0005764 lysosome | IDA PMID:15052268 Mutations in VPS33B, encoding a regulator of SNARE-dependent... | MODIFY | Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein. Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein. Proposed replacements: lysosomal membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane PMID:17897319 Integral and associated lysosomal membrane proteins |
| GO:0005764 lysosome | IDA PMID:16542649 Palmitoyl protein thioesterase 1 (PPT1) deficiency causes en... | MODIFY | Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein. Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein. Proposed replacements: lysosomal membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane PMID:17897319 Integral and associated lysosomal membrane proteins |
| GO:0005770 late endosome | IDA PMID:16542649 Palmitoyl protein thioesterase 1 (PPT1) deficiency causes en... | MODIFY | Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane. Reason: Use late endosome membrane to capture the integral membrane localization. Proposed replacements: late endosome membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane; Endosome membrane; Late endosome membrane PMID:16176980 localizes to late endosomes (LEs)/lysosomes |
| GO:0005764 lysosome | IDA PMID:15292400 Alfy, a novel FYVE-domain-containing protein associated with... | MODIFY | Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein. Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein. Proposed replacements: lysosomal membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane PMID:17897319 Integral and associated lysosomal membrane proteins |
| GO:0005770 late endosome | IDA PMID:15292400 Alfy, a novel FYVE-domain-containing protein associated with... | MODIFY | Summary: Late endosome is correct as a broad compartment, but LAMP1 is specifically on the late endosome membrane. Reason: Use late endosome membrane to capture the integral membrane localization. Proposed replacements: late endosome membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane; Endosome membrane; Late endosome membrane PMID:16176980 localizes to late endosomes (LEs)/lysosomes |
| GO:0005764 lysosome | TAS PMID:3131762 Molecular cloning of cDNAs encoding lamp A, a human lysosoma... | MODIFY | Summary: Lysosome is correct but less precise than lysosomal membrane for this type I membrane glycoprotein. Reason: Use the more specific lysosomal membrane term for a single-pass LAMP-family membrane protein. Proposed replacements: lysosomal membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane PMID:17897319 Integral and associated lysosomal membrane proteins |
| GO:0005886 plasma membrane | TAS PMID:3174652 Derived protein sequence, oligosaccharides, and membrane ins... | KEEP AS NON CORE | Summary: plasma membrane is supported during LAMP1 cycling and cytotoxic granule exocytosis, but it is secondary to the lysosomal membrane location. Reason: Retain as non-core surface/exocytic localization rather than the defining LAMP1 location. Supporting Evidence: PMID:23847195 Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage file:human/LAMP1/LAMP1-uniprot.txt Cell membrane; Cytolytic granule membrane |
| GO:0016020 membrane | TAS PMID:3174652 Derived protein sequence, oligosaccharides, and membrane ins... | MODIFY | Summary: membrane is true but too general for LAMP1. Reason: Replace the broad membrane/vesicle term with lysosomal membrane, the informative core location. Proposed replacements: lysosomal membrane Supporting Evidence: file:human/LAMP1/LAMP1-uniprot.txt Lysosome membrane PMID:17897319 Integral and associated lysosomal membrane proteins |
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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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