ID   SESN1_MACFA             Reviewed;         492 AA.
AC   Q4R6P7;
DT   04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 1.
DT   03-AUG-2022, entry version 58.
DE   RecName: Full=Sestrin-1 {ECO:0000305};
DE            EC=1.11.1.- {ECO:0000250|UniProtKB:P58004};
GN   Name=SESN1 {ECO:0000250|UniProtKB:P58004};
GN   ORFNames=QtsA-17454 {ECO:0000312|EMBL:BAE01227.1};
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RG   International consortium for macaque cDNA sequencing and analysis;
RT   "DNA sequences of macaque genes expressed in brain or testis and its
RT   evolutionary implications.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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. This
CC       stress-inducible metabolic regulator may also play a role in protection
CC       against oxidative and genotoxic stresses. 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. Moreover, may prevent the accumulation of reactive oxygen
CC       species (ROS) through the alkylhydroperoxide reductase activity born by
CC       the N-terminal domain of the protein. Was originally reported to
CC       contribute to oxidative stress resistance by reducing PRDX1. However,
CC       this could not be confirmed. {ECO:0000250|UniProtKB:P58004}.
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. Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function
CC       as a guanine nucleotide dissociation inhibitor for RRAGs and regulate
CC       them. Interacts with KEAP1, RBX1 and SQSTM1; in the SQSTM1-dependent
CC       autophagic degradation of KEAP1. May interact with PRDX1.
CC       {ECO:0000250|UniProtKB:Q9Y6P5}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y6P5}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q9Y6P5}.
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; AB169134; BAE01227.1; -; mRNA.
DR   RefSeq; XP_015303861.1; XM_015448375.1.
DR   AlphaFoldDB; Q4R6P7; -.
DR   SMR; Q4R6P7; -.
DR   STRING; 9541.XP_005551598.1; -.
DR   PRIDE; Q4R6P7; -.
DR   GeneID; 101865915; -.
DR   KEGG; mcf:101865915; -.
DR   CTD; 27244; -.
DR   VEuPathDB; HostDB:ENSMFAG00000031220; -.
DR   eggNOG; KOG3746; Eukaryota.
DR   OMA; CIFGIRH; -.
DR   Proteomes; UP000233100; Chromosome 4.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0070728; F:leucine binding; ISS:UniProtKB.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0098869; P:cellular oxidant detoxification; ISS:UniProtKB.
DR   GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB.
DR   GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB.
DR   GO; GO:0072593; P:reactive oxygen species metabolic process; ISS: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   2: Evidence at transcript level;
KW   Cytoplasm; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome.
FT   CHAIN           1..492
FT                   /note="Sestrin-1"
FT                   /id="PRO_0000231008"
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:0000250|UniProtKB:Q9Y6P5"
FT   MOD_RES         314
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6P5"
SQ   SEQUENCE   492 AA;  56712 MW;  C785D1E94A996446 CRC64;
     MRLATAANEA YTAPLAVSEL LGCKQCGGGR DHDEELGIRI 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 VFSSDDDEVT PARDVSRHFE DTSYGYKDFS RHGMHVPTFR VQDYCWEDHG
     YSLVNRLYPD VGQLIDEKFH IAYNLTYNTM AMHKDVDTSM LRRAIWNYIH CMFGIRYDDY
     DYGEINQLLD RSFKVYIKTV VCTPEKVTKR MYESFWRQFK HSEKVHVNLL LIEARMQAEL
     LYALRAITRY MT