{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P58004","secondaryAccessions":["Q5T7D0","Q96SI5"],"uniProtkbId":"SESN2_HUMAN","entryAudit":{"firstPublicDate":"2001-04-27","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2001-04-27","entryVersion":192,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Sestrin-2"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"26612684"}],"value":"1.11.1.-"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12203114"}],"value":"Hypoxia-induced gene"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:20746"}],"value":"SESN2"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12203114"}],"value":"Hi95"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12607115"}],"value":"SEST2"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15105503"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18692468"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19113821"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23274085"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24947615"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25263562"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25457612"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26449471"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26586190"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35114100"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35831510"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36528027"}],"value":"Functions as an intracellular leucine sensor that negatively regulates the mTORC1 signaling pathway through the GATOR complex (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26586190, PubMed:26612684, PubMed:31586034, PubMed:35114100, PubMed:35831510, PubMed:36528027). In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents mTORC1 signaling (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26586190, PubMed:26612684, PubMed:31586034, PubMed:35114100, PubMed:35831510, PubMed:36528027). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190, PubMed:35114100, PubMed:35831510, PubMed:36528027). This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. May negatively regulate protein translation in response to endoplasmic reticulum stress, via mTORC1 (PubMed:24947615). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress (PubMed:18692468). Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (PubMed:26612684). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (PubMed:19113821)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"a hydroperoxide + L-cysteinyl-[protein] = S-hydroxy-L-cysteinyl-[protein] + an alcohol","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:67124"},{"database":"Rhea","id":"RHEA-COMP:10131"},{"database":"Rhea","id":"RHEA-COMP:17193"},{"database":"ChEBI","id":"CHEBI:29950"},{"database":"ChEBI","id":"CHEBI:30879"},{"database":"ChEBI","id":"CHEBI:35924"},{"database":"ChEBI","id":"CHEBI:61973"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:67125"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"26612684"}]}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P58043"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15105503"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18692468"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23274085"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25040165"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25259925"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25263562"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25457612"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26449471"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35114100"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35831510"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36528027"}],"value":"Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by leucine (PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:35114100, PubMed:35831510, PubMed:36528027). Conveys leucine availability via direct interaction with SEH1L and WDR24 components of the GATOR2 complex (PubMed:35831510, PubMed:36528027). Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them (PubMed:25259925). May interact with the TORC2 complex (By similarity). Interacts with KEAP1, RBX1, SQSTM and ULK1; to regulate the degradation of KEAP1 (PubMed:23274085, PubMed:25040165). May also associate with the complex composed of TSC1, TSC2 and the AMP-responsive protein kinase/AMPK to regulate TORC1 signaling (PubMed:18692468). May interact with PRDX1 (PubMed:15105503)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P58004","intActId":"EBI-3939642"},"interactantTwo":{"uniProtKBAccession":"Q14145","geneName":"KEAP1","intActId":"EBI-751001"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P58004","intActId":"EBI-3939642"},"interactantTwo":{"uniProtKBAccession":"Q9NXC5","geneName":"MIOS","intActId":"EBI-2515122"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P58004","intActId":"EBI-3939642"},"interactantTwo":{"uniProtKBAccession":"P62877","geneName":"RBX1","intActId":"EBI-398523"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P58004","intActId":"EBI-3939642"},"interactantTwo":{"uniProtKBAccession":"Q13501","geneName":"SQSTM1","intActId":"EBI-307104"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P58004","intActId":"EBI-3939642"},"interactantTwo":{"uniProtKBAccession":"Q96S15","geneName":"WDR24","intActId":"EBI-746424"},"numberOfExperiments":18,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P58004","intActId":"EBI-3939642"},"interactantTwo":{"uniProtKBAccession":"P62878","geneName":"Rbx1","intActId":"EBI-2507414"},"numberOfExperiments":3,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P58004","intActId":"EBI-3939642"},"interactantTwo":{"uniProtKBAccession":"O70405","geneName":"Ulk1","intActId":"EBI-8390771"},"numberOfExperiments":5,"organismDiffer":true}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15105503"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12607115"}],"value":"Widely expressed"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12203114"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24947615"}],"value":"Up-regulated by hypoxia and DNA damage (PubMed:12203114). Up-regulated by treatments inducing endoplasmic reticulum stress (PubMed:24947615)"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"value":"The N-terminal domain has an alkylhydroperoxide reductase activity"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"value":"The C-terminal domain mediates interaction with GATOR2 through which it regulates TORC1 signaling"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25040165"}],"value":"Phosphorylated by ULK1 at multiple sites"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31586034"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35114100"}],"value":"Ubiquitinated at Lys-175 by RNF167 via 'Lys-63'-linked polyubiquitination in response to leucine deprivation: ubiquitination promotes SESN2-interaction with the GATOR2 complex, leading to inhibit the TORC1 signaling pathway (PubMed:35114100). Deubiquitinated at Lys-175 by STAMBPL1, promoting the TORC1 signaling pathway (PubMed:35114100). Ubiquitinated by RNF186; ubiquitination mediates proteasomal degradation (PubMed:31586034)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the sestrin family"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAB55438.1","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":480,"modifier":"EXACT"}},"description":"Sestrin-2","featureId":"PRO_0000221181"},{"type":"Region","location":{"start":{"value":20,"modifier":"EXACT"},"end":{"value":45,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":66,"modifier":"EXACT"},"end":{"value":239,"modifier":"EXACT"}},"description":"N-terminal domain; mediates the alkylhydroperoxide reductase activity","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}]},{"type":"Region","location":{"start":{"value":222,"modifier":"EXACT"},"end":{"value":252,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":272,"modifier":"EXACT"},"end":{"value":291,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":308,"modifier":"EXACT"},"end":{"value":480,"modifier":"EXACT"}},"description":"C-terminal domain; mediates TORC1 regulation","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}]},{"type":"Active site","location":{"start":{"value":125,"modifier":"EXACT"},"end":{"value":125,"modifier":"EXACT"}},"description":"Cysteine sulfenic acid (-SOH) intermediate","evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"26612684"}]},{"type":"Binding site","location":{"start":{"value":374,"modifier":"EXACT"},"end":{"value":377,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:57427"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26586190"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"5DJ4"}],"ligand":{"name":"L-leucine","id":"ChEBI:CHEBI:57427"}},{"type":"Binding site","location":{"start":{"value":386,"modifier":"EXACT"},"end":{"value":386,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:57427"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26586190"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"5DJ4"}],"ligand":{"name":"L-leucine","id":"ChEBI:CHEBI:57427"}},{"type":"Binding site","location":{"start":{"value":451,"modifier":"EXACT"},"end":{"value":451,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:57427"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26586190"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"5DJ4"}],"ligand":{"name":"L-leucine","id":"ChEBI:CHEBI:57427"}},{"type":"Modified residue","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":1,"modifier":"EXACT"}},"description":"N-acetylmethionine","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"22814378"}]},{"type":"Modified residue","location":{"start":{"value":249,"modifier":"EXACT"},"end":{"value":249,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"23186163"},{"evidenceCode":"ECO:0007744","source":"PubMed","id":"24275569"}]},{"type":"Cross-link","location":{"start":{"value":175,"modifier":"EXACT"},"end":{"value":175,"modifier":"EXACT"}},"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35114100"}]},{"type":"Natural variant","location":{"start":{"value":320,"modifier":"EXACT"},"end":{"value":320,"modifier":"EXACT"}},"description":"in dbSNP:rs2274848","featureCrossReferences":[{"database":"dbSNP","id":"rs2274848"}],"featureId":"VAR_022101","alternativeSequence":{"originalSequence":"T","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":13,"modifier":"EXACT"},"end":{"value":13,"modifier":"EXACT"}},"description":"About two-fold prolonged half-life in cycloheximide/CHX time course.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26586190"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":86,"modifier":"EXACT"},"end":{"value":86,"modifier":"EXACT"}},"description":"Loss of leucine-binding.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26586190"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":87,"modifier":"EXACT"},"end":{"value":87,"modifier":"EXACT"}},"description":"No effect on the ability to inhibit the TORC1 signaling pathway.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"P","alternativeSequences":["S"]}},{"type":"Mutagenesis","location":{"start":{"value":113,"modifier":"EXACT"},"end":{"value":113,"modifier":"EXACT"}},"description":"No effect on the ability to inhibit the TORC1 signaling pathway; when associated with C-128.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":125,"modifier":"EXACT"},"end":{"value":125,"modifier":"EXACT"}},"description":"Decreased alkylhydroperoxide reductase activity and loss of the ability to decrease intracellular reactive oxygen species. No effect on interaction with the GATOR2 complex. No effect on inhibition of TOR signaling.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15105503"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18692468"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"C","alternativeSequences":["S"]}},{"type":"Mutagenesis","location":{"start":{"value":127,"modifier":"EXACT"},"end":{"value":127,"modifier":"EXACT"}},"description":"Decreased alkylhydroperoxide reductase activity. No effect on the ability to inhibit the TORC1 signaling pathway.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"Y","alternativeSequences":["F"]}},{"type":"Mutagenesis","location":{"start":{"value":128,"modifier":"EXACT"},"end":{"value":128,"modifier":"EXACT"}},"description":"No effect on the ability to inhibit the TORC1 signaling pathway; when associated with E-113.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"L","alternativeSequences":["C"]}},{"type":"Mutagenesis","location":{"start":{"value":132,"modifier":"EXACT"},"end":{"value":132,"modifier":"EXACT"}},"description":"Decreased alkylhydroperoxide reductase activity. No effect on the ability to inhibit the TORC1 signaling pathway.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":175,"modifier":"EXACT"},"end":{"value":175,"modifier":"EXACT"}},"description":"Abolished 'Lys-63'-linked ubiquitination by RNF167.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35114100"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":190,"modifier":"EXACT"},"end":{"value":190,"modifier":"EXACT"}},"description":"Loss of interaction with GATOR2. No effect on leucine-binding. Unable to mediate leucine-induced inhibition of the TORC1 signaling pathway.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26449471"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36528027"}],"alternativeSequence":{"originalSequence":"S","alternativeSequences":["W"]}},{"type":"Mutagenesis","location":{"start":{"value":204,"modifier":"EXACT"},"end":{"value":204,"modifier":"EXACT"}},"description":"No effect on alkylhydroperoxide reductase activity. No effect on the ability to inhibit the TORC1 signaling pathway.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"C","alternativeSequences":["S"]}},{"type":"Mutagenesis","location":{"start":{"value":214,"modifier":"EXACT"},"end":{"value":214,"modifier":"EXACT"}},"description":"No effect on alkylhydroperoxide reductase activity.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"C","alternativeSequences":["S"]}},{"type":"Mutagenesis","location":{"start":{"value":258,"modifier":"EXACT"},"end":{"value":258,"modifier":"EXACT"}},"description":"No effect on the ability to inhibit the TORC1 signaling pathway; when associated with L-259 and R-261.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"V","alternativeSequences":["R"]}},{"type":"Mutagenesis","location":{"start":{"value":259,"modifier":"EXACT"},"end":{"value":259,"modifier":"EXACT"}},"description":"No effect on the ability to inhibit the TORC1 signaling pathway; when associated with R-258 and R-261.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"E","alternativeSequences":["L"]}},{"type":"Mutagenesis","location":{"start":{"value":261,"modifier":"EXACT"},"end":{"value":261,"modifier":"EXACT"}},"description":"Decreased leucine-binding. Promotes interaction with RNF167.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26449471"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35114100"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36528027"}],"alternativeSequence":{"originalSequence":"L","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":261,"modifier":"EXACT"},"end":{"value":261,"modifier":"EXACT"}},"description":"No effect on the ability to inhibit the TORC1 signaling pathway; when associated with R-258 and L-259.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"L","alternativeSequences":["R"]}},{"type":"Mutagenesis","location":{"start":{"value":262,"modifier":"EXACT"},"end":{"value":264,"modifier":"EXACT"}},"description":"No effect on the ability to inhibit the TORC1 signaling pathway.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"MER","alternativeSequences":["LMM"]}},{"type":"Mutagenesis","location":{"start":{"value":264,"modifier":"EXACT"},"end":{"value":264,"modifier":"EXACT"}},"description":"No effect on the ability to inhibit the TORC1 signaling pathway.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["P"]}},{"type":"Mutagenesis","location":{"start":{"value":314,"modifier":"EXACT"},"end":{"value":314,"modifier":"EXACT"}},"description":"No effect on ability to decrease intracellular reactive oxygen species.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15105503"}],"alternativeSequence":{"originalSequence":"C","alternativeSequences":["S"]}},{"type":"Mutagenesis","location":{"start":{"value":336,"modifier":"EXACT"},"end":{"value":337,"modifier":"EXACT"}},"description":"No effect on the ability to inhibit the TORC1 signaling pathway.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"TF","alternativeSequences":["AA"]}},{"type":"Mutagenesis","location":{"start":{"value":340,"modifier":"EXACT"},"end":{"value":341,"modifier":"EXACT"}},"description":"No effect on the ability to inhibit the TORC1 signaling pathway.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"QD","alternativeSequences":["AA"]}},{"type":"Mutagenesis","location":{"start":{"value":373,"modifier":"EXACT"},"end":{"value":373,"modifier":"EXACT"}},"description":"No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-376.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26612684"}],"alternativeSequence":{"originalSequence":"L","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":374,"modifier":"EXACT"},"end":{"value":374,"modifier":"EXACT"}},"description":"Loss of leucine-binding. 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