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Sestrin-2 (EC 1.11.1.15)

 SESN2_PONAB             Reviewed;         480 AA.
Q5RCB4;
12-JUN-2007, integrated into UniProtKB/Swiss-Prot.
21-DEC-2004, sequence version 1.
07-JUN-2017, entry version 48.
RecName: Full=Sestrin-2 {ECO:0000305};
EC=1.11.1.15 {ECO:0000250|UniProtKB:P58004};
Name=SESN2 {ECO:0000250|UniProtKB:P58004};
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Pongo.
NCBI_TaxID=9601;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Kidney;
The German cDNA consortium;
Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
-!- FUNCTION: Functions as an intracellular leucine sensor that
negatively regulates the TORC1 signaling pathway through the GATOR
complex. In absence of leucine, binds the GATOR subcomplex GATOR2
and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts
its interaction with GATOR2 thereby activating the TORC1 signaling
pathway. 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 TORC1. 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. May also mediate TP53 inhibition of TORC1
signaling upon genotoxic stress. Has an alkylhydroperoxide
reductase activity born by the N-terminal domain of the protein.
Was originally reported to contribute to oxidative stress
resistance by reducing PRDX1. However, this could not be
confirmed. {ECO:0000250|UniProtKB:P58004}.
-!- CATALYTIC ACTIVITY: 2 R'-SH + ROOH = R'-S-S-R' + H(2)O + ROH.
{ECO:0000250|UniProtKB:P58004}.
-!- SUBUNIT: Interacts with the GATOR2 complex which is composed of
MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively
regulated by leucine. Interacts with RRAGA, RRAGB, RRAGC and
RRAGD; may function as a guanine nucleotide dissociation inhibitor
for RRAGs and regulate them. May interact with the TORC2 complex.
Interacts with KEAP1, RBX1, SQSTM and ULK1; to regulate the
degradation of KEAP1. May also associate with the complex composed
of TSC1, TSC2 and the AMP-responsive protein kinase/AMPK to
regulate TORC1 signaling. May interact with PRDX1.
{ECO:0000250|UniProtKB:P58004}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P58004}.
-!- DOMAIN: Composed of an N-terminal domain that has an
alkylhydroperoxide reductase activity and a C-terminal domain that
mediates interaction with GATOR2 through which it regulates TORC1
signaling. {ECO:0000250|UniProtKB:P58004}.
-!- PTM: Phosphorylated by ULK1 at multiple sites.
{ECO:0000250|UniProtKB:P58004}.
-!- SIMILARITY: Belongs to the sestrin family. {ECO:0000305}.
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EMBL; CR858363; CAH90593.1; -; mRNA.
RefSeq; NP_001125320.1; NM_001131848.1.
UniGene; Pab.10775; -.
ProteinModelPortal; Q5RCB4; -.
SMR; Q5RCB4; -.
STRING; 9601.ENSPPYP00000001899; -.
GeneID; 100172219; -.
KEGG; pon:100172219; -.
CTD; 83667; -.
eggNOG; KOG3746; Eukaryota.
eggNOG; ENOG410XP7Z; LUCA.
HOVERGEN; HBG054648; -.
InParanoid; Q5RCB4; -.
KO; K20394; -.
Proteomes; UP000001595; Unplaced.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0005634; C:nucleus; IEA:InterPro.
GO; GO:0070728; F:leucine binding; ISS:UniProtKB.
GO; GO:0016684; F:oxidoreductase activity, acting on peroxide as acceptor; ISS:UniProtKB.
GO; GO:0051920; F:peroxiredoxin activity; IEA:UniProtKB-EC.
GO; GO:1990253; P:cellular response to leucine starvation; ISS:UniProtKB.
GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB.
GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB.
GO; GO:1902010; P:negative regulation of translation in response to endoplasmic reticulum stress; ISS:UniProtKB.
GO; GO:0016239; P:positive regulation of macroautophagy; ISS:UniProtKB.
GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISS:UniProtKB.
GO; GO:0036091; P:positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress; ISS:UniProtKB.
GO; GO:0072593; P:reactive oxygen species metabolic process; ISS:UniProtKB.
GO; GO:0001932; P:regulation of protein phosphorylation; ISS:UniProtKB.
GO; GO:1901031; P:regulation of response to reactive oxygen species; IEA:InterPro.
Gene3D; 1.20.1290.10; -; 1.
InterPro; IPR029032; AhpD-like.
InterPro; IPR006730; Sestrin.
Pfam; PF04636; PA26; 1.
SUPFAM; SSF69118; SSF69118; 1.
2: Evidence at transcript level;
Acetylation; Complete proteome; Cytoplasm; Oxidoreductase;
Phosphoprotein; Reference proteome.
CHAIN 1 480 Sestrin-2.
/FTId=PRO_0000290025.
REGION 66 239 N-terminal domain; mediates the
alkylhydroperoxide reductase activity.
{ECO:0000250|UniProtKB:P58004}.
REGION 308 480 C-terminal domain; mediates TORC1
regulation.
{ECO:0000250|UniProtKB:P58004}.
REGION 374 377 Leucine-binding.
{ECO:0000250|UniProtKB:P58004}.
ACT_SITE 125 125 Cysteine sulfenic acid (-SOH)
intermediate.
{ECO:0000250|UniProtKB:P58004}.
BINDING 386 386 Leucine; via carbonyl oxygen.
{ECO:0000250|UniProtKB:P58004}.
BINDING 451 451 Leucine. {ECO:0000250|UniProtKB:P58004}.
MOD_RES 1 1 N-acetylmethionine.
{ECO:0000250|UniProtKB:P58004}.
MOD_RES 249 249 Phosphoserine.
{ECO:0000250|UniProtKB:P58004}.
SEQUENCE 480 AA; 54452 MW; 38990A9ED8A38C90 CRC64;
MIVADSECRA ELKDYLRFAP GGVGDSGPGE EQRESRARRG PRGPSAFIPV EEVLREGAES
LEQHLGLEAL MSSGRVDNLA VVMGLHPDYF TSFWRLHYLP LHTDGPLASS WRHYIAIMAA
ARHQCSYLVG SHMAEFLQTG GDPEWLLGLH RAPEKLRKLS EINKLLAHRP WLITKEHIQA
LLKTGEHTWS LAELIQALVL LTHCHSLSSF VFGCGILPEG DADGSPAPQA PTPPSEQSSP
PSRDPLNNSG GFESARDVEA LMERMRQLQE SLLRDEGTSQ EEMESRFELE KSESLLVTPS
ADILEPSPHP DMLCFVEDPA FGYEDFTRRG AQAPPTFRAQ DYTWEDHGYS LIQRLYPEGG
QLLDEKFQAA YSLTYNTIAM LSGVDTSVLR RAIWNYIHCV FGIRYDDYDY GEVNQLLERN
LKVYIKTVAC YPEKTTRRMY NLFWRHFRHS EKVHVNLLLL EARMQAALLY ALRAITRYMT


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