SESN1_HUMAN
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 03-AUG-2022, entry version 169.
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},
GN SEST1 {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}.
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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; Q9Y6P5; -.
DR PeptideAtlas; Q9Y6P5; -.
DR PRIDE; Q9Y6P5; -.
DR ProteomicsDB; 86756; -. [Q9Y6P5-1]
DR ProteomicsDB; 86757; -. [Q9Y6P5-2]
DR ProteomicsDB; 86758; -. [Q9Y6P5-3]
DR Antibodypedia; 32228; 276 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 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; CIFGIRH; -.
DR OrthoDB; 588598at2759; -.
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; 15 hits in 1088 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 197 other tissues.
DR Genevisible; Q9Y6P5; HS.
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; -; 1.
DR InterPro; IPR029032; AhpD-like.
DR InterPro; IPR006730; Sestrin.
DR PANTHER; PTHR12474; PTHR12474; 1.
DR Pfam; PF04636; PA26; 1.
DR SUPFAM; SSF69118; SSF69118; 1.
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
