LRSAM1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Electronic transfer of cytoplasmic localization from UniProt; the correct primary compartment, redundant with experimental IDA/EXP evidence. Reason: Correct primary localization; LRSAM1 is a cytoplasmic E3 ligase. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269\|PubMed:15256501
GO:0061630 ubiquitin protein ligase activity	IEA GO_REF:0000003	ACCEPT	Summary: EC-mapping (EC 2.3.2.27) electronic assignment of ubiquitin protein ligase activity. LRSAM1 is a genuine RING-type E3 ligase, so this is correct and core. Reason: Core molecular function; LRSAM1 has intrinsic RING E3 ligase activity (EC 2.3.2.27), redundant with the experimental EXP/IDA evidence. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	KEEP AS NON CORE	Summary: High-throughput proteome-scale interactome interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative per curation guidelines.
GO:0005515 protein binding	IPI PMID:16713569 A protein-protein interaction network for human inherited at...	KEEP AS NON CORE	Summary: Interaction from an inherited-ataxia/Purkinje-degeneration interaction network. Bare protein binding is uninformative. Reason: High-throughput/network interactome; bare protein binding is uninformative.
GO:0005515 protein binding	IPI PMID:19549727 Analysis of the human E2 ubiquitin conjugating enzyme protei...	KEEP AS NON CORE	Summary: Interaction from an E2 ubiquitin-conjugating enzyme interaction network; relevant to LRSAM1's role as a RING E3 that pairs with E2 enzymes. Bare protein binding is uninformative. Reason: Records E2-E3 interaction(s) consistent with LRSAM1's ligase function, but the bare term is uninformative.
GO:0005515 protein binding	IPI PMID:19690564 A comprehensive framework of E2-RING E3 interactions of the ...	KEEP AS NON CORE	Summary: Interaction from a comprehensive E2-RING E3 interaction framework; relevant to LRSAM1 as a RING E3. Bare protein binding is uninformative. Reason: Records E2-RING interactions consistent with LRSAM1's ligase function, but the bare term is uninformative.
GO:0005515 protein binding	IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi...	KEEP AS NON CORE	Summary: Interaction from a genome-wide YFP fluorescence complementation telomere-signaling screen. Bare protein binding is uninformative. Reason: High-throughput screen interaction; bare protein binding is uninformative.
GO:0005515 protein binding	IPI PMID:25260751 The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in respon...	KEEP AS NON CORE	Summary: Interaction reported in a study of MEKK1 PHD/TAB1 ubiquitination. Bare protein binding is uninformative. Reason: Interactome-type interaction; bare protein binding is uninformative.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: Proteome-scale interactome interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative.
GO:0005515 protein binding	IPI PMID:27615052 A novel missense mutation of CMT2P alters transcription mach...	KEEP AS NON CORE	Summary: Interaction reported in a CMT2P (Charcot-Marie-Tooth) LRSAM1 mutation study. Bare protein binding is uninformative. Reason: Disease-study interaction; bare protein binding is uninformative.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Binary interactome reference map interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	KEEP AS NON CORE	Summary: Neurodegeneration interactome interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: Cell-specific proteome-scale interactome interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative.
GO:0016567 protein ubiquitination	IEA GO_REF:0000041	KEEP AS NON CORE	Summary: UniPathway-derived generic protein ubiquitination process; correct for an E3 ligase but generic. Reason: Correct but generic; the specific autoubiquitination/polyubiquitination and xenophagy annotations better capture LRSAM1's role. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt PATHWAY: Protein modification; protein ubiquitination.
GO:0005737 cytoplasm	EXP PMID:27615052 A novel missense mutation of CMT2P alters transcription mach...	ACCEPT	Summary: Experimental evidence for cytoplasmic localization of LRSAM1. Core compartment. Reason: Direct experimental support for the primary cytoplasmic localization. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt Cytoplasm {ECO:0000269\|PubMed:15256501, ECO:0000269\|PubMed:27615052}
GO:0061630 ubiquitin protein ligase activity	EXP PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase, regulates recept...	ACCEPT	Summary: Experimental evidence that LRSAM1/Tal is a TSG101-specific E3 ubiquitin ligase. Core molecular function. Reason: Core molecular function directly supported; LRSAM1 has intrinsic RING E3 ligase activity (monoubiquitinates TSG101). Supporting Evidence: PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding
GO:0005515 protein binding	IPI PMID:23245322 The LRR and RING domain protein LRSAM1 is an E3 ligase cruci...	KEEP AS NON CORE	Summary: Interaction(s) reported in the foundational xenophagy study. Bare protein binding is uninformative. Reason: From the key antibacterial-autophagy paper, but the bare term is uninformative; the xenophagy/ligase annotations capture the function. Supporting Evidence: PMID:23245322 LRSAM1 localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal
GO:0005515 protein binding	IPI PMID:25484098 PHF23 (plant homeodomain finger protein 23) negatively regul...	KEEP AS NON CORE	Summary: Interaction with PHF23, the PHD finger protein that ubiquitinates and degrades LRSAM1 to negatively regulate autophagy. Bare protein binding is uninformative. Reason: Records a real regulatory interaction (PHF23-LRSAM1) but the bare term is uninformative. Supporting Evidence: PMID:25484098 PHF23 ... negatively regulates cell autophagy by promoting ubiquitination and degradation of E3 ligase LRSAM1
GO:0051865 protein autoubiquitination	IDA PMID:23245322 The LRR and RING domain protein LRSAM1 is an E3 ligase cruci...	ACCEPT	Summary: Direct evidence of LRSAM1 RING-dependent (auto)ubiquitination activity in the xenophagy study. Reflects intrinsic E3 activity. Reason: Directly demonstrated; autoubiquitination is a hallmark of an active RING E3 ligase and supports LRSAM1's core catalytic function. Supporting Evidence: PMID:23245322 these functions require LRSAM1's leucine-rich repeat and RING domains, respectively
GO:0061630 ubiquitin protein ligase activity	IDA PMID:23245322 The LRR and RING domain protein LRSAM1 is an E3 ligase cruci...	ACCEPT	Summary: Direct evidence that LRSAM1 acts as the E3 ligase generating the ubiquitin signal around intracellular bacteria. Core molecular function. Reason: Core molecular function directly demonstrated; the RING domain is required to generate the bacteria-associated ubiquitin signal. Supporting Evidence: PMID:23245322 We identify LRSAM1 as the E3 ligase responsible for anti-Salmonella autophagy-associated ubiquitination
GO:1904417 positive regulation of xenophagy	IMP PMID:23245322 The LRR and RING domain protein LRSAM1 is an E3 ligase cruci...	ACCEPT	Summary: Mutant-phenotype evidence (LRSAM1-deficient cells) that LRSAM1 is required for the ubiquitin signal driving xenophagy of intracellular Salmonella. Core biological process. Reason: Core biological process; LRSAM1 generates the bacteria-associated ubiquitin signal that triggers antibacterial autophagy (xenophagy). Supporting Evidence: PMID:23245322 LRSAM1 is required for ubiquitination associated with intracellular bacteria but dispensable for ubiquitination of aggregated proteins
GO:0098792 xenophagy	IMP PMID:23245322 The LRR and RING domain protein LRSAM1 is an E3 ligase cruci...	NEW	Summary: LRSAM1 is required for ubiquitin-dependent antibacterial autophagy of cytosolic intracellular bacteria, the base xenophagy process. Reason: PN correctly flagged that GOA already supports positive regulation of xenophagy but lacks the base xenophagy process term. The regulation annotation and primary paper support adding GO:0098792 as the more direct process context. Supporting Evidence: PMID:23245322 LRSAM1 is therefore a bacterial recognition protein and ubiquitin ligase that defends the cytoplasm from invasive pathogens
GO:2000786 positive regulation of autophagosome assembly	IMP PMID:25484098 PHF23 (plant homeodomain finger protein 23) negatively regul...	KEEP AS NON CORE	Summary: Mutant-phenotype evidence that LRSAM1 promotes autophagy (its degradation by PHF23 suppresses autophagy). Downstream consequence of LRSAM1's ubiquitin-signaling function. Reason: Real and consistent with LRSAM1 promoting autophagy, but a downstream/secondary process relative to its core E3-ligase ubiquitin-signaling activity that initiates xenophagy. Supporting Evidence: PMID:25484098 PHF23 ... negatively regulates cell autophagy by promoting ubiquitination and degradation of E3 ligase LRSAM1
GO:0016020 membrane	IDA PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase, regulates recept...	KEEP AS NON CORE	Summary: Direct evidence of membrane-associated (submembranal ring) localization. Consistent with LRSAM1's ESCRT/TSG101-related role at membranes. Reason: Real membrane association (submembranal ring), but a generic compartment term secondary to the primary cytoplasmic/bacterial localization. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt Displays a punctuate distribution and localizes to a submembranal ring
GO:0000209 protein polyubiquitination	IDA PMID:18077552 Regulation of Tsg101 expression by the steadiness box: a rol...	ACCEPT	Summary: Direct evidence of LRSAM1-mediated polyubiquitination (TSG101 regulation context). Reflects core E3 ligase activity. Reason: Directly demonstrated ubiquitination activity consistent with LRSAM1's core RING E3 ligase function. Supporting Evidence: PMID:18077552 Regulation of Tsg101 expression by the steadiness box: a role of Tsg101-associated ligase
GO:0004842 ubiquitin-protein transferase activity	IDA PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase, regulates recept...	ACCEPT	Summary: Direct evidence of LRSAM1/Tal ubiquitin-transferase activity toward TSG101. Core molecular function (LRSAM1 is a catalytic RING E3, unlike adaptor-only F-box proteins). Reason: Core molecular function; LRSAM1's RING domain catalyzes ubiquitin transfer to substrates (TSG101). This is genuine catalytic activity, appropriately annotated. Supporting Evidence: PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding
GO:0004842 ubiquitin-protein transferase activity	IDA PMID:18077552 Regulation of Tsg101 expression by the steadiness box: a rol...	ACCEPT	Summary: Direct evidence of LRSAM1 ubiquitin-transferase activity in TSG101 regulation. Core molecular function. Reason: Core molecular function; directly demonstrated ubiquitin transfer activity of the RING E3 ligase. Supporting Evidence: PMID:18077552 a role of Tsg101-associated ligase
GO:0005515 protein binding	IPI PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase, regulates recept...	KEEP AS NON CORE	Summary: Interaction with TSG101 (the substrate of LRSAM1/Tal). Bare protein binding is uninformative. Reason: Records the functionally central LRSAM1-TSG101 substrate interaction, but the bare term is uninformative; the ubiquitination/endocytosis annotations capture the function. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt Interacts with TSG101 (PubMed:17556548)
GO:0005515 protein binding	IPI PMID:18077552 Regulation of Tsg101 expression by the steadiness box: a rol...	KEEP AS NON CORE	Summary: Interaction with TSG101 in the steadiness-box regulation study. Bare protein binding is uninformative. Reason: Records the LRSAM1-TSG101 interaction but the bare term is uninformative. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt Interacts with TSG101 (PubMed:17556548)
GO:0005737 cytoplasm	IDA PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase, regulates recept...	ACCEPT	Summary: Direct evidence of cytoplasmic localization (punctate distribution / submembranal ring). Core compartment. Reason: Direct experimental support for the primary cytoplasmic localization. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt Displays a punctuate distribution and localizes to a submembranal ring
GO:0005737 cytoplasm	IDA PMID:18077552 Regulation of Tsg101 expression by the steadiness box: a rol...	ACCEPT	Summary: Direct evidence of cytoplasmic localization in the TSG101-regulation study. Core compartment. Reason: Direct experimental support for the primary cytoplasmic localization. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0030163 protein catabolic process	IMP PMID:18077552 Regulation of Tsg101 expression by the steadiness box: a rol...	KEEP AS NON CORE	Summary: Mutant-phenotype evidence linking LRSAM1 to regulation of TSG101 protein levels (steadiness box). Reflects LRSAM1's ubiquitination-driven control of substrate abundance. Reason: Generic catabolic-process term; consequence of LRSAM1's ubiquitination activity on TSG101 rather than a distinct core process. Supporting Evidence: PMID:18077552 Regulation of Tsg101 expression by the steadiness box
GO:0045806 negative regulation of endocytosis	IMP PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase, regulates recept...	KEEP AS NON CORE	Summary: Mutant-phenotype evidence that LRSAM1/Tal regulates receptor endocytosis by monoubiquitinating TSG101 and inactivating its endocytic-sorting function. Reason: Real ESCRT/TSG101-related role (regulation of EGFR endocytic sorting), but a secondary function distinct from the core antibacterial-xenophagy ubiquitin-ligase role. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors)
GO:0046755 viral budding	IMP PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase, regulates recept...	KEEP AS NON CORE	Summary: Mutant-phenotype evidence that LRSAM1/Tal regulates retrovirus (HIV-1) budding by ubiquitinating TSG101 and inactivating its exocytic-sorting function. Reason: Real ESCRT/TSG101-related role in retroviral budding, but a secondary function distinct from the core antibacterial-xenophagy ligase role. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt exocytic (HIV-1 viral proteins) cargos
GO:0051865 protein autoubiquitination	IDA PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase, regulates recept...	ACCEPT	Summary: Direct evidence of LRSAM1/Tal autoubiquitination, a hallmark of an active RING E3 ligase. Reason: Directly demonstrated; autoubiquitination supports LRSAM1's core catalytic RING E3 ligase activity. Supporting Evidence: PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase
GO:0070086 ubiquitin-dependent endocytosis	IDA PMID:15256501 Tal, a Tsg101-specific E3 ubiquitin ligase, regulates recept...	KEEP AS NON CORE	Summary: Direct evidence linking LRSAM1/Tal to ubiquitin-dependent endocytic regulation via TSG101 monoubiquitination. Reason: Real ESCRT/TSG101-related endocytic role, but secondary to LRSAM1's core antibacterial-xenophagy ubiquitin-ligase function. Supporting Evidence: file:human/LRSAM1/LRSAM1-uniprot.txt regulates receptor endocytosis and retrovirus budding

Gene Description

Existing Annotations Review

Core Functions

Acts as a TSG101-specific E3 ligase (Tal) that monoubiquitinates the ESCRT-I component TSG101, inactivating its ability to sort endocytic (EGFR) and exocytic (HIV-1) cargo, thereby regulating receptor endocytosis and retroviral budding.

References

Suggested Questions for Experts

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📚 Additional Documentation

Notes

Pn Notes

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