SESN1_XENLA
ID SESN1_XENLA Reviewed; 481 AA.
AC P58003; Q5D077;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Sestrin-1 {ECO:0000305};
DE EC=1.11.1.- {ECO:0000250|UniProtKB:P58004};
DE AltName: Full=XPA26 {ECO:0000303|PubMed:11165487};
DE AltName: Full=p53-regulated protein PA26 {ECO:0000303|PubMed:11165487};
GN Name=sesn1 {ECO:0000250|UniProtKB:P58004};
GN Synonyms=pa26 {ECO:0000303|PubMed:11165487};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11165487; DOI=10.1016/s0925-4773(00)00519-0;
RA Hikasa H., Taira M.;
RT "A Xenopus homolog of a human p53-activated gene, PA26, is specifically
RT expressed in the notochord.";
RL Mech. Dev. 100:309-312(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: May function as an intracellular leucine sensor that
CC negatively regulates the TORC1 signaling pathway through the GATOR
CC complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and
CC prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its
CC interaction with GATOR2 thereby activating the TORC1 signaling pathway.
CC This stress-inducible metabolic regulator may also play a role in
CC protection against oxidative and genotoxic stresses. May prevent the
CC accumulation of reactive oxygen species (ROS) through the
CC alkylhydroperoxide reductase activity born by the N-terminal domain of
CC the protein. {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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y6P5}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9Y6P5}.
CC -!- DEVELOPMENTAL STAGE: At zygotic stage; specifically expressed in the
CC notochord. Maternal transcripts are detected at cleavage stages and
CC reduced during gastrulation.
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; AB048259; BAB33008.1; -; mRNA.
DR EMBL; BC056061; AAH56061.1; -; mRNA.
DR RefSeq; NP_001079869.1; NM_001086400.1.
DR AlphaFoldDB; P58003; -.
DR SMR; P58003; -.
DR DNASU; 379559; -.
DR GeneID; 379559; -.
DR KEGG; xla:379559; -.
DR CTD; 379559; -.
DR Xenbase; XB-GENE-866080; sesn1.L.
DR OMA; CIFGIRH; -.
DR OrthoDB; 588598at2759; -.
DR Proteomes; UP000186698; Chromosome 5L.
DR Bgee; 379559; Expressed in spleen and 19 other tissues.
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:1904262; P:negative regulation of TORC1 signaling; 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; Reference proteome.
FT CHAIN 1..481
FT /note="Sestrin-1"
FT /id="PRO_0000221180"
FT REGION 63..244
FT /note="N-terminal domain; may mediate the
FT alkylhydroperoxide reductase activity"
FT /evidence="ECO:0000250|UniProtKB:P58004"
FT REGION 295..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 310..481
FT /note="C-terminal domain; mediates TORC1 regulation"
FT /evidence="ECO:0000250|UniProtKB:P58004"
FT ACT_SITE 122
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000250|UniProtKB:P58004"
FT BINDING 375..378
FT /ligand="L-leucine"
FT /ligand_id="ChEBI:CHEBI:57427"
FT /evidence="ECO:0000250|UniProtKB:P58004"
FT BINDING 387
FT /ligand="L-leucine"
FT /ligand_id="ChEBI:CHEBI:57427"
FT /evidence="ECO:0000250|UniProtKB:P58004"
FT BINDING 452
FT /ligand="L-leucine"
FT /ligand_id="ChEBI:CHEBI:57427"
FT /evidence="ECO:0000250|UniProtKB:P58004"
SQ SEQUENCE 481 AA; 55459 MW; 8C175801BBFAFE9D CRC64;
MRLSPRAALS SPEIICSRCS QSCNNKELGI RIPRPLGQGP SRFVPEEEIL QLASEDANMH
SVFADAFTDL GRLDNITLVM VFHPQYLESF LKTQHYLLQM DGPLSPCYQH YIGIMAASRH
QCSYLVNLHV NDFIHHGGDQ KWLNGLENAP QKLRNLGELN KMLAHRPWLI TKEHIKQLLK
AGEHSWSLAE LIHAIVLLAH YHSLASFTFG CGINPEIHSN GGHTFRPPSV SNYCICDITN
GNHGTEGHLP VGIVMPTDST CEVEALMVKM KQLQEGRDEE EASQEEMATR FEREKTESMV
FSTEDEDPPP DIDVSRHFED TSYGYKDFSR RGMHVPTFRV QDYSWEDHGY SLVNRLYPDV
GQLLDEKFHI AYNLTYNTMA MHKDVDTSTL RRAVWNYVHC MFGIRYDDYD YGEINQLLDR
SFKVYIKNVV CSPEKTSKRM YDGFWRQFKH SEKVHVNLLL MEARMQGELL YALRAITRYM
T
