ID SESN1_HUMAN Reviewed; 492 AA. AC Q9Y6P5; Q2M2B7; Q5T316; Q9NV00; Q9UPD5; Q9Y6P6; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 27-APR-2001, sequence version 2. DT 27-MAR-2024, entry version 178. DE RecName: Full=Sestrin-1 {ECO:0000305}; DE EC=1.11.1.- {ECO:0000250|UniProtKB:P58004}; DE AltName: Full=p53-regulated protein PA26 {ECO:0000303|PubMed:9926927}; GN Name=SESN1 {ECO:0000312|HGNC:HGNC:21595}; GN Synonyms=PA26 {ECO:0000303|PubMed:9926927}, SEST1 GN {ECO:0000303|PubMed:12607115}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS T1; T2 AND T3), AND INDUCTION. RX PubMed=9926927; DOI=10.1038/sj.onc.1202274; RA Velasco-Miguel S., Buckbinder L., Jean P., Gelbert L., Talbott R., RA Laidlaw J., Seizinger B., Kley N.; RT "PA26, a novel target of the p53 tumor suppressor and member of the GADD RT family of DNA damage and growth arrest inducible genes."; RL Oncogene 18:127-137(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-44, AND TISSUE SPECIFICITY. RX PubMed=12607115; DOI=10.1007/s00439-003-0917-5; RA Peeters H., Debeer P., Bairoch A., Wilquet V., Huysmans C., Parthoens E., RA Fryns J.-P., Gewillig M., Nakamura Y., Niikawa N., Van De Ven W., RA Devriendt K.; RT "PA26 is a candidate gene for heterotaxia in humans: identification of a RT novel PA26-related gene family in human and mouse."; RL Hum. Genet. 112:573-580(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM T1). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 309-492. RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP FUNCTION, INTERACTION WITH PRDX1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP CYS-130. RX PubMed=15105503; DOI=10.1126/science.1095569; RA Budanov A.V., Sablina A.A., Feinstein E., Koonin E.V., Chumakov P.M.; RT "Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of RT bacterial AhpD."; RL Science 304:596-600(2004). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [10] RP FUNCTION, AND INTERACTION WITH KEAP1; RBX1 AND SQSTM1. RX PubMed=23274085; DOI=10.1016/j.cmet.2012.12.002; RA Bae S.H., Sung S.H., Oh S.Y., Lim J.M., Lee S.K., Park Y.N., Lee H.E., RA Kang D., Rhee S.G.; RT "Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation RT of Keap1 and prevent oxidative liver damage."; RL Cell Metab. 17:73-84(2013). RN [11] RP INTERACTION WITH RRAGA; RRAGB; RRAGC AND RRAGD. RX PubMed=25259925; DOI=10.1016/j.cell.2014.08.038; RA Peng M., Yin N., Li M.O.; RT "Sestrins function as guanine nucleotide dissociation inhibitors for Rag RT GTPases to control mTORC1 signaling."; RL Cell 159:122-133(2014). RN [12] RP FUNCTION, AND INTERACTION WITH GATOR2 COMPLEX. RX PubMed=25263562; DOI=10.1016/j.celrep.2014.09.014; RA Chantranupong L., Wolfson R.L., Orozco J.M., Saxton R.A., Scaria S.M., RA Bar-Peled L., Spooner E., Isasa M., Gygi S.P., Sabatini D.M.; RT "The Sestrins interact with GATOR2 to negatively regulate the amino-acid- RT sensing pathway upstream of mTORC1."; RL Cell Rep. 9:1-8(2014). RN [13] RP FUNCTION, INTERACTION WITH GATOR2 COMPLEX, AND LEUCINE-BINDING. RX PubMed=26449471; DOI=10.1126/science.aab2674; RA Wolfson R.L., Chantranupong L., Saxton R.A., Shen K., Scaria S.M., RA Cantor J.R., Sabatini D.M.; RT "Sestrin2 is a leucine sensor for the mTORC1 pathway."; RL Science 351:43-48(2016). CC -!- FUNCTION: Functions as an intracellular leucine sensor that negatively CC regulates the TORC1 signaling pathway through the GATOR complex. In CC absence of leucine, binds the GATOR subcomplex GATOR2 and prevents CC TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction CC with GATOR2 thereby activating the TORC1 signaling pathway CC (PubMed:25263562, PubMed:26449471). This stress-inducible metabolic CC regulator may also play a role in protection against oxidative and CC genotoxic stresses (By similarity). May positively regulate the CC transcription by NFE2L2 of genes involved in the response to oxidative CC stress by facilitating the SQSTM1-mediated autophagic degradation of CC KEAP1 (PubMed:23274085). Moreover, may prevent the accumulation of CC reactive oxygen species (ROS) through the alkylhydroperoxide reductase CC activity born by the N-terminal domain of the protein (By similarity). CC Was originally reported to contribute to oxidative stress resistance by CC reducing PRDX1 (PubMed:15105503). However, this could not be confirmed CC (By similarity). {ECO:0000250|UniProtKB:P58004, CC ECO:0000269|PubMed:15105503, ECO:0000269|PubMed:23274085, CC ECO:0000269|PubMed:25263562, ECO:0000269|PubMed:26449471}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a hydroperoxide + L-cysteinyl-[protein] = an alcohol + S- CC hydroxy-L-cysteinyl-[protein]; Xref=Rhea:RHEA:67124, Rhea:RHEA- CC COMP:10131, Rhea:RHEA-COMP:17193, ChEBI:CHEBI:29950, CC ChEBI:CHEBI:30879, ChEBI:CHEBI:35924, ChEBI:CHEBI:61973; CC Evidence={ECO:0000250|UniProtKB:P58004}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67125; CC Evidence={ECO:0000250|UniProtKB:P58004}; CC -!- SUBUNIT: Interacts with the GATOR2 complex which is composed of MIOS, CC SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated CC by leucine (PubMed:25263562, PubMed:26449471). Interacts with RRAGA, CC RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide CC dissociation inhibitor for RRAGs and regulate them (PubMed:25259925). CC Interacts with KEAP1, RBX1 and SQSTM1; in the SQSTM1-dependent CC autophagic degradation of KEAP1 (PubMed:23274085). May interact with CC PRDX1 (PubMed:15105503). {ECO:0000269|PubMed:15105503, CC ECO:0000269|PubMed:23274085, ECO:0000269|PubMed:25259925, CC ECO:0000269|PubMed:25263562, ECO:0000269|PubMed:26449471}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9926927}. Cytoplasm CC {ECO:0000269|PubMed:15105503}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=T2; CC IsoId=Q9Y6P5-1; Sequence=Displayed; CC Name=T1; CC IsoId=Q9Y6P5-2; Sequence=VSP_006059; CC Name=T3; CC IsoId=Q9Y6P5-3; Sequence=VSP_006060; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:12607115}. CC -!- INDUCTION: Isoform T2 and isoform T3 are induced by genotoxic stress CC (UV, gamma-irradiation and cytotoxic drugs) in a p53/TP53-dependent CC manner. Isoform T1 is not induced by p53/TP53. CC {ECO:0000269|PubMed:9926927}. CC -!- DOMAIN: The N-terminal domain may have an alkylhydroperoxide reductase CC activity. {ECO:0000250|UniProtKB:P58004}. CC -!- DOMAIN: The C-terminal domain mediates interaction with GATOR2 through CC which it regulates TORC1 signaling. {ECO:0000250|UniProtKB:P58004}. CC -!- SIMILARITY: Belongs to the sestrin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF033122; AAD04812.1; -; mRNA. DR EMBL; AF033120; AAD04810.1; -; mRNA. DR EMBL; AF033121; AAD04811.1; -; mRNA. DR EMBL; AL390208; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW48367.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48368.1; -; Genomic_DNA. DR EMBL; BC112036; AAI12037.1; -; mRNA. DR EMBL; BC113569; AAI13570.1; -; mRNA. DR EMBL; AK001886; BAA91961.1; -; mRNA. DR CCDS; CCDS5070.1; -. [Q9Y6P5-2] DR CCDS; CCDS56444.1; -. [Q9Y6P5-3] DR CCDS; CCDS56445.1; -. [Q9Y6P5-1] DR RefSeq; NP_001186862.1; NM_001199933.1. [Q9Y6P5-1] DR RefSeq; NP_001186863.1; NM_001199934.1. [Q9Y6P5-3] DR RefSeq; NP_055269.1; NM_014454.2. [Q9Y6P5-2] DR AlphaFoldDB; Q9Y6P5; -. DR SMR; Q9Y6P5; -. DR BioGRID; 118092; 10. DR DIP; DIP-62046N; -. DR IntAct; Q9Y6P5; 6. DR STRING; 9606.ENSP00000393762; -. DR iPTMnet; Q9Y6P5; -. DR PhosphoSitePlus; Q9Y6P5; -. DR BioMuta; SESN1; -. DR DMDM; 13633953; -. DR EPD; Q9Y6P5; -. DR jPOST; Q9Y6P5; -. DR MassIVE; Q9Y6P5; -. DR MaxQB; Q9Y6P5; -. DR PaxDb; 9606-ENSP00000393762; -. DR PeptideAtlas; Q9Y6P5; -. DR ProteomicsDB; 86756; -. [Q9Y6P5-1] DR ProteomicsDB; 86757; -. [Q9Y6P5-2] DR ProteomicsDB; 86758; -. [Q9Y6P5-3] DR Pumba; Q9Y6P5; -. DR Antibodypedia; 32228; 330 antibodies from 31 providers. DR DNASU; 27244; -. DR Ensembl; ENST00000302071.6; ENSP00000306734.2; ENSG00000080546.14. [Q9Y6P5-3] DR Ensembl; ENST00000356644.7; ENSP00000349061.7; ENSG00000080546.14. [Q9Y6P5-1] DR Ensembl; ENST00000436639.7; ENSP00000393762.2; ENSG00000080546.14. [Q9Y6P5-2] DR GeneID; 27244; -. DR KEGG; hsa:27244; -. DR MANE-Select; ENST00000436639.7; ENSP00000393762.2; NM_014454.3; NP_055269.1. [Q9Y6P5-2] DR UCSC; uc003pst.5; human. [Q9Y6P5-1] DR AGR; HGNC:21595; -. DR CTD; 27244; -. DR DisGeNET; 27244; -. DR GeneCards; SESN1; -. DR HGNC; HGNC:21595; SESN1. DR HPA; ENSG00000080546; Low tissue specificity. DR MIM; 606103; gene. DR neXtProt; NX_Q9Y6P5; -. DR OpenTargets; ENSG00000080546; -. DR PharmGKB; PA134927596; -. DR VEuPathDB; HostDB:ENSG00000080546; -. DR eggNOG; KOG3746; Eukaryota. DR GeneTree; ENSGT00950000183168; -. DR HOGENOM; CLU_020429_2_0_1; -. DR InParanoid; Q9Y6P5; -. DR OMA; CDQVTQV; -. DR OrthoDB; 3032841at2759; -. DR PhylomeDB; Q9Y6P5; -. DR TreeFam; TF314230; -. DR PathwayCommons; Q9Y6P5; -. DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes. DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1. DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway. DR SignaLink; Q9Y6P5; -. DR SIGNOR; Q9Y6P5; -. DR BioGRID-ORCS; 27244; 16 hits in 1166 CRISPR screens. DR ChiTaRS; SESN1; human. DR GeneWiki; SESN1; -. DR GenomeRNAi; 27244; -. DR Pharos; Q9Y6P5; Tbio. DR PRO; PR:Q9Y6P5; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q9Y6P5; Protein. DR Bgee; ENSG00000080546; Expressed in skeletal muscle tissue of rectus abdominis and 199 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0070728; F:leucine binding; IDA:UniProtKB. DR GO; GO:0016684; F:oxidoreductase activity, acting on peroxide as acceptor; IBA:GO_Central. DR GO; GO:0098869; P:cellular oxidant detoxification; IMP:UniProtKB. DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB. DR GO; GO:0042149; P:cellular response to glucose starvation; IMP:UniProtKB. DR GO; GO:0071233; P:cellular response to leucine; IBA:GO_Central. DR GO; GO:1990253; P:cellular response to leucine starvation; IBA:GO_Central. DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:UniProtKB. DR GO; GO:0016239; P:positive regulation of macroautophagy; IBA:GO_Central. DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:UniProtKB. DR GO; GO:1901031; P:regulation of response to reactive oxygen species; IEA:InterPro. DR Gene3D; 1.20.1290.10; AhpD-like; 1. DR InterPro; IPR029032; AhpD-like. DR InterPro; IPR006730; Sestrin. DR PANTHER; PTHR12474; P53 REGULATED PA26 NUCLEAR PROTEIN SESTRIN; 1. DR PANTHER; PTHR12474:SF3; SESTRIN-1; 1. DR Pfam; PF04636; PA26; 1. DR SUPFAM; SSF69118; AhpD-like; 1. DR Genevisible; Q9Y6P5; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Nucleus; Oxidoreductase; Phosphoprotein; KW Reference proteome. FT CHAIN 1..492 FT /note="Sestrin-1" FT /id="PRO_0000221178" FT REGION 71..252 FT /note="N-terminal domain; may mediate the FT alkylhydroperoxide reductase activity" FT /evidence="ECO:0000250|UniProtKB:P58004" FT REGION 321..492 FT /note="C-terminal domain; mediates TORC1 regulation" FT /evidence="ECO:0000250|UniProtKB:P58004" FT ACT_SITE 130 FT /note="Cysteine sulfenic acid (-SOH) intermediate" FT /evidence="ECO:0000250|UniProtKB:P58004" FT BINDING 386..389 FT /ligand="L-leucine" FT /ligand_id="ChEBI:CHEBI:57427" FT /evidence="ECO:0000250|UniProtKB:P58004" FT BINDING 398 FT /ligand="L-leucine" FT /ligand_id="ChEBI:CHEBI:57427" FT /evidence="ECO:0000250|UniProtKB:P58004" FT BINDING 463 FT /ligand="L-leucine" FT /ligand_id="ChEBI:CHEBI:57427" FT /evidence="ECO:0000250|UniProtKB:P58004" FT MOD_RES 293 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 314 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT VAR_SEQ 1..66 FT /note="Missing (in isoform T3)" FT /evidence="ECO:0000303|PubMed:9926927" FT /id="VSP_006060" FT VAR_SEQ 1..34 FT /note="MRLAAAANEAYTAPLAVSGLLGCKQCGGGRDQDE -> MAEGENEVRWDGLC FT SRDSTTRETALENIRQTILRKTEYLRSVKETPHRPSDGLSNTESSDGLNKLLAHLLMLS FT KRCPFKDVREKSEFILKSIQ (in isoform T1)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9926927" FT /id="VSP_006059" FT VARIANT 44 FT /note="L -> I (in dbSNP:rs2273668)" FT /evidence="ECO:0000269|PubMed:12607115" FT /id="VAR_014210" FT MUTAGEN 130 FT /note="C->S: Loss of the ability to decrease intracellular FT reactive oxygen species." FT /evidence="ECO:0000269|PubMed:15105503" SQ SEQUENCE 492 AA; 56557 MW; 824CF6513634C35E CRC64; MRLAAAANEA YTAPLAVSGL LGCKQCGGGR DQDEELGIRI PRPLGQGPSR FIPEKEILQV GSEDAQMHAL FADSFAALGR LDNITLVMVF HPQYLESFLK TQHYLLQMDG PLPLHYRHYI GIMAAARHQC SYLVNLHVND FLHVGGDPKW LNGLENAPQK LQNLGELNKV LAHRPWLITK EHIEGLLKAE EHSWSLAELV HAVVLLTHYH SLASFTFGCG ISPEIHCDGG HTFRPPSVSN YCICDITNGN HSVDEMPVNS AENVSVSDSF FEVEALMEKM RQLQECRDEE EASQEEMASR FEIEKRESMF VFSSDDEEVT PARAVSRHFE DTSYGYKDFS RHGMHVPTFR VQDYCWEDHG YSLVNRLYPD VGQLIDEKFH IAYNLTYNTM AMHKDVDTSM LRRAIWNYIH CMFGIRYDDY DYGEINQLLD RSFKVYIKTV VCTPEKVTKR MYDSFWRQFK HSEKVHVNLL LIEARMQAEL LYALRAITRY MT //