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Protein

Sestrin-2

Gene

SESN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190). 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 (PubMed:24947615). 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 (PubMed:23274085). May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress (PubMed:18692468). Has an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (PubMed:26612684). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (PubMed:19113821).10 Publications

Catalytic activityi

2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei125 – 1251Cysteine sulfenic acid (-SOH) intermediate1 Publication
Binding sitei386 – 3861Leucine; via carbonyl oxygenCombined sources1 Publication
Binding sitei451 – 4511LeucineCombined sources1 Publication

GO - Molecular functioni

  • leucine binding Source: UniProtKB
  • oxidoreductase activity, acting on peroxide as acceptor Source: UniProtKB
  • sulfiredoxin activity Source: UniProtKB

GO - Biological processi

  • autophagy Source: Ensembl
  • cellular oxidant detoxification Source: UniProtKB
  • cellular response to amino acid stimulus Source: UniProtKB
  • cellular response to leucine Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
  • fatty acid beta-oxidation Source: Ensembl
  • glucose import Source: Ensembl
  • mitochondrial DNA metabolic process Source: Ensembl
  • negative regulation of TORC1 signaling Source: UniProtKB
  • negative regulation of translation in response to endoplasmic reticulum stress Source: UniProtKB
  • positive regulation of macroautophagy Source: UniProtKB
  • positive regulation of protein localization to nucleus Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress Source: UniProtKB
  • protein kinase B signaling Source: Ensembl
  • reactive oxygen species metabolic process Source: UniProtKB
  • regulation of cAMP-dependent protein kinase activity Source: Ensembl
  • regulation of gluconeogenesis involved in cellular glucose homeostasis Source: Ensembl
  • regulation of protein phosphorylation Source: UniProtKB
  • regulation of response to reactive oxygen species Source: InterPro
  • response to glucose Source: Ensembl
  • response to insulin Source: Ensembl
  • triglyceride homeostasis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Enzyme and pathway databases

ReactomeiR-HSA-5628897. TP53 Regulates Metabolic Genes.

Names & Taxonomyi

Protein namesi
Recommended name:
Sestrin-2Curated (EC:1.11.1.151 Publication)
Alternative name(s):
Hypoxia-induced gene1 Publication
Gene namesi
Name:SESN2Imported
Synonyms:Hi951 Publication, SEST21 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:20746. SESN2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • mitochondrion Source: Ensembl
  • nucleus Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi86 – 861H → A: Loss of leucine-binding. 1 Publication
Mutagenesisi87 – 871P → S: No effect on the ability to inhibit the TORC1 signaling pathway. 1 Publication
Mutagenesisi113 – 1131H → E: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with C-128. 1 Publication
Mutagenesisi125 – 1251C → S: Decreased alkylhydroperoxide reductase activity and loss of the ability to decrease intracellular reactive oxygen species. No effect on interaction with the GATOR2 complex. No effect on inhibition of TOR signaling. 3 Publications
Mutagenesisi127 – 1271Y → F: Decreased alkylhydroperoxide reductase activity. No effect on the ability to inhibit the TORC1 signaling pathway. 1 Publication
Mutagenesisi128 – 1281L → C: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with E-113. 1 Publication
Mutagenesisi132 – 1321H → A: Decreased alkylhydroperoxide reductase activity. No effect on the ability to inhibit the TORC1 signaling pathway. 1 Publication
Mutagenesisi190 – 1901S → W: Loss of interaction with GATOR2. No effect on leucine-binding. Unable to mediate leucine-induced inhibition of the TORC1 signaling pathway. 1 Publication
Mutagenesisi204 – 2041C → S: No effect on alkylhydroperoxide reductase activity. No effect on the ability to inhibit the TORC1 signaling pathway. 1 Publication
Mutagenesisi214 – 2141C → S: No effect on alkylhydroperoxide reductase activity. 1 Publication
Mutagenesisi258 – 2581V → R: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with L-259 and R-261. 1 Publication
Mutagenesisi259 – 2591E → L: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with R-258 and R-261. 1 Publication
Mutagenesisi261 – 2611L → A: Decreased leucine-binding. 1 Publication
Mutagenesisi261 – 2611L → R: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with R-258 and L-259. 1 Publication
Mutagenesisi262 – 2643MER → LMM: No effect on the ability to inhibit the TORC1 signaling pathway. 1 Publication
Mutagenesisi264 – 2641R → P: No effect on the ability to inhibit the TORC1 signaling pathway. 1 Publication
Mutagenesisi314 – 3141C → S: No effect on ability to decrease intracellular reactive oxygen species. 1 Publication
Mutagenesisi336 – 3372TF → AA: No effect on the ability to inhibit the TORC1 signaling pathway. 1 Publication
Mutagenesisi340 – 3412QD → AA: No effect on the ability to inhibit the TORC1 signaling pathway. 1 Publication
Mutagenesisi373 – 3731L → A: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-376. 1 Publication
Mutagenesisi374 – 3741T → A: Loss of leucine-binding. Constituvely interacts with the GATOR2 complex. 1 Publication
Mutagenesisi375 – 3751Y → A: Loss of leucine-binding. 1 Publication
Mutagenesisi376 – 3761N → A: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-373. 1 Publication
Mutagenesisi385 – 3851D → A: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-387. 1 Publication
Mutagenesisi386 – 3861T → A: Loss of leucine-binding. Constituvely interacts with the GATOR2 complex. 1 Publication
Mutagenesisi387 – 3871S → A: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-385. 1 Publication
Mutagenesisi390 – 3901R → A: Loss of leucine-binding. Constituvely interacts with the GATOR2 complex. 1 Publication
Mutagenesisi399 – 3991C → S: No effect on alkylhydroperoxide reductase activity. Altered ability to decrease intracellular reactive oxygen species. No effect on the ability to inhibit the TORC1 signaling pathway. 2 Publications
Mutagenesisi406 – 4072DD → AA: Loss of interaction with the GATOR2 complex. No effect on leucine-binding. 1 Publication
Mutagenesisi406 – 4061D → A: No effect on alkylhydroperoxide reductase activity. Loss of interaction with the GATOR2 complex. Unable to inhibit the TORC1 signaling pathway. 1 Publication
Mutagenesisi407 – 4071D → A: No effect on alkylhydroperoxide reductase activity. Loss of interaction with the GATOR2 complex. Unable to inhibit the TORC1 signaling pathway. 1 Publication
Mutagenesisi409 – 4091D → A: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-411 and A-415. 1 Publication
Mutagenesisi411 – 4111G → A: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-409 and A-415. 1 Publication
Mutagenesisi415 – 4151Q → A: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-409 and A-411. 1 Publication
Mutagenesisi419 – 4191R → A: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-422 and A-426. 1 Publication
Mutagenesisi422 – 4221K → A: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-419 and A-426. 1 Publication
Mutagenesisi426 – 4261K → A: No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-419 and A-422. 1 Publication
Mutagenesisi430 – 4301C → S: No effect on alkylhydroperoxide reductase activity. Altered ability to decrease intracellular reactive oxygen species. No effect on the ability to inhibit the TORC1 signaling pathway. 2 Publications
Mutagenesisi444 – 4441W → E: Loss of leucine-binding. 1 Publication
Mutagenesisi444 – 4441W → L: Decreased affinity for leucine. Requires increased leucine concentration to dissociate from GATOR2 and activate TORC1 signaling. 1 Publication
Mutagenesisi451 – 4511E → A: Decreased leucine-binding. 1 Publication
Mutagenesisi451 – 4511E → Q: Loss of leucine-binding. Constituvely interacts with the GATOR2 complex. 1 Publication

Organism-specific databases

PharmGKBiPA134882791.

Polymorphism and mutation databases

BioMutaiSESN2.
DMDMi13633882.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 480480Sestrin-2PRO_0000221181Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineCombined sources
Modified residuei249 – 2491PhosphoserineCombined sources

Post-translational modificationi

Phosphorylated by ULK1 at multiple sites.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP58004.
MaxQBiP58004.
PaxDbiP58004.
PeptideAtlasiP58004.
PRIDEiP58004.

PTM databases

iPTMnetiP58004.
PhosphoSiteiP58004.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Inductioni

Up-regulated by hypoxia and DNA damage (PubMed:12203114). Up-regulated by treatments inducing endoplasmic reticulum stress (PubMed:24947615).2 Publications

Gene expression databases

BgeeiP58004.
CleanExiHS_SESN2.
GenevisibleiP58004. HS.

Organism-specific databases

HPAiHPA018191.

Interactioni

Subunit structurei

Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by leucine (PubMed:25263562, PubMed:25457612, PubMed:26449471). Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them (PubMed:25259925). May interact with the TORC2 complex (By similarity). Interacts with KEAP1, RBX1, SQSTM and ULK1; to regulate the degradation of KEAP1 (PubMed:23274085, PubMed:25040165). May also associate with the complex composed of TSC1, TSC2 and the AMP-responsive protein kinase/AMPK to regulate TORC1 signaling (PubMed:18692468). May interact with PRDX1 (PubMed:15105503).By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SQSTM1Q135015EBI-3939642,EBI-307104
Ulk1O704055EBI-3939642,EBI-8390771From a different organism.

Protein-protein interaction databases

BioGridi123724. 12 interactions.
IntActiP58004. 7 interactions.
MINTiMINT-4715291.
STRINGi9606.ENSP00000253063.

Structurei

Secondary structure

1
480
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi68 – 714Combined sources
Turni72 – 743Combined sources
Helixi78 – 836Combined sources
Helixi87 – 10216Combined sources
Helixi109 – 12113Combined sources
Turni122 – 1243Combined sources
Helixi126 – 13813Combined sources
Helixi143 – 1475Combined sources
Helixi149 – 1513Combined sources
Helixi154 – 1574Combined sources
Helixi160 – 1689Combined sources
Helixi170 – 1723Combined sources
Helixi175 – 1828Combined sources
Beta strandi185 – 1873Combined sources
Helixi191 – 21323Combined sources
Beta strandi228 – 2303Combined sources
Beta strandi235 – 2373Combined sources
Helixi257 – 27014Combined sources
Helixi283 – 29210Combined sources
Helixi313 – 3153Combined sources
Beta strandi328 – 3303Combined sources
Helixi339 – 3413Combined sources
Turni344 – 3474Combined sources
Helixi348 – 3558Combined sources
Helixi357 – 37115Combined sources
Beta strandi378 – 3803Combined sources
Helixi387 – 40014Combined sources
Helixi411 – 4166Combined sources
Helixi419 – 43012Combined sources
Helixi432 – 4343Combined sources
Helixi437 – 4426Combined sources
Helixi449 – 47931Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
5CUFX-ray3.50A/B/C/D/E1-480[»]
5DJ4X-ray2.70A/B/C/D/E1-480[»]
ProteinModelPortaliP58004.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni66 – 239174N-terminal domain; mediates the alkylhydroperoxide reductase activity1 PublicationAdd
BLAST
Regioni308 – 480173C-terminal domain; mediates TORC1 regulation1 PublicationAdd
BLAST
Regioni374 – 3774Leucine-bindingCombined sources1 Publication

Domaini

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.1 Publication

Sequence similaritiesi

Belongs to the sestrin family.Curated

Phylogenomic databases

eggNOGiKOG3746. Eukaryota.
ENOG410XP7Z. LUCA.
GeneTreeiENSGT00440000040103.
HOGENOMiHOG000232949.
HOVERGENiHBG054648.
InParanoidiP58004.
KOiK10141.
OMAiASSWRHY.
OrthoDBiEOG7SBNNF.
PhylomeDBiP58004.
TreeFamiTF314230.

Family and domain databases

Gene3Di1.20.1290.10. 1 hit.
InterProiIPR029032. AhpD-like.
IPR006730. Sestrin.
[Graphical view]
PfamiPF04636. PA26. 1 hit.
[Graphical view]
SUPFAMiSSF69118. SSF69118. 1 hit.

Sequencei

Sequence statusi: Complete.

P58004-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIVADSECRA ELKDYLRFAP GGVGDSGPGE EQRESRARRG PRGPSAFIPV
60 70 80 90 100
EEVLREGAES LEQHLGLEAL MSSGRVDNLA VVMGLHPDYF TSFWRLHYLL
110 120 130 140 150
LHTDGPLASS WRHYIAIMAA ARHQCSYLVG SHMAEFLQTG GDPEWLLGLH
160 170 180 190 200
RAPEKLRKLS EINKLLAHRP WLITKEHIQA LLKTGEHTWS LAELIQALVL
210 220 230 240 250
LTHCHSLSSF VFGCGILPEG DADGSPAPQA PTPPSEQSSP PSRDPLNNSG
260 270 280 290 300
GFESARDVEA LMERMQQLQE SLLRDEGTSQ EEMESRFELE KSESLLVTPS
310 320 330 340 350
ADILEPSPHP DMLCFVEDPT FGYEDFTRRG AQAPPTFRAQ DYTWEDHGYS
360 370 380 390 400
LIQRLYPEGG QLLDEKFQAA YSLTYNTIAM HSGVDTSVLR RAIWNYIHCV
410 420 430 440 450
FGIRYDDYDY GEVNQLLERN LKVYIKTVAC YPEKTTRRMY NLFWRHFRHS
460 470 480
EKVHVNLLLL EARMQAALLY ALRAITRYMT
Length:480
Mass (Da):54,494
Last modified:April 27, 2001 - v1
Checksum:i9C13371316D84060
GO

Sequence cautioni

The sequence BAB55438.1 differs from that shown. Reason: Erroneous initiation. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti320 – 3201T → A.
Corresponds to variant rs2274848 [ dbSNP | Ensembl ].
VAR_022101

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY123223 mRNA. Translation: AAM92261.1.
AL136551 mRNA. Translation: CAB66486.1.
AK027896 mRNA. Translation: BAB55438.1. Different initiation.
AK025640 mRNA. No translation available.
AK315710 mRNA. Translation: BAG38070.1.
AL353622 Genomic DNA. Translation: CAI19133.1.
CH471059 Genomic DNA. Translation: EAX07703.1.
BC013304 mRNA. Translation: AAH13304.1.
BC033719 mRNA. Translation: AAH33719.1.
CCDSiCCDS321.1.
RefSeqiNP_113647.1. NM_031459.4.
UniGeneiHs.469543.

Genome annotation databases

EnsembliENST00000253063; ENSP00000253063; ENSG00000130766.
GeneIDi83667.
KEGGihsa:83667.
UCSCiuc001bps.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY123223 mRNA. Translation: AAM92261.1.
AL136551 mRNA. Translation: CAB66486.1.
AK027896 mRNA. Translation: BAB55438.1. Different initiation.
AK025640 mRNA. No translation available.
AK315710 mRNA. Translation: BAG38070.1.
AL353622 Genomic DNA. Translation: CAI19133.1.
CH471059 Genomic DNA. Translation: EAX07703.1.
BC013304 mRNA. Translation: AAH13304.1.
BC033719 mRNA. Translation: AAH33719.1.
CCDSiCCDS321.1.
RefSeqiNP_113647.1. NM_031459.4.
UniGeneiHs.469543.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
5CUFX-ray3.50A/B/C/D/E1-480[»]
5DJ4X-ray2.70A/B/C/D/E1-480[»]
ProteinModelPortaliP58004.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123724. 12 interactions.
IntActiP58004. 7 interactions.
MINTiMINT-4715291.
STRINGi9606.ENSP00000253063.

PTM databases

iPTMnetiP58004.
PhosphoSiteiP58004.

Polymorphism and mutation databases

BioMutaiSESN2.
DMDMi13633882.

Proteomic databases

EPDiP58004.
MaxQBiP58004.
PaxDbiP58004.
PeptideAtlasiP58004.
PRIDEiP58004.

Protocols and materials databases

DNASUi83667.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000253063; ENSP00000253063; ENSG00000130766.
GeneIDi83667.
KEGGihsa:83667.
UCSCiuc001bps.4. human.

Organism-specific databases

CTDi83667.
GeneCardsiSESN2.
HGNCiHGNC:20746. SESN2.
HPAiHPA018191.
MIMi607767. gene.
neXtProtiNX_P58004.
PharmGKBiPA134882791.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3746. Eukaryota.
ENOG410XP7Z. LUCA.
GeneTreeiENSGT00440000040103.
HOGENOMiHOG000232949.
HOVERGENiHBG054648.
InParanoidiP58004.
KOiK10141.
OMAiASSWRHY.
OrthoDBiEOG7SBNNF.
PhylomeDBiP58004.
TreeFamiTF314230.

Enzyme and pathway databases

ReactomeiR-HSA-5628897. TP53 Regulates Metabolic Genes.

Miscellaneous databases

ChiTaRSiSESN2. human.
GeneWikiiSESN2.
GenomeRNAii83667.
PROiP58004.
SOURCEiSearch...

Gene expression databases

BgeeiP58004.
CleanExiHS_SESN2.
GenevisibleiP58004. HS.

Family and domain databases

Gene3Di1.20.1290.10. 1 hit.
InterProiIPR029032. AhpD-like.
IPR006730. Sestrin.
[Graphical view]
PfamiPF04636. PA26. 1 hit.
[Graphical view]
SUPFAMiSSF69118. SSF69118. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability."
    Budanov A.V., Shoshani T., Faerman A., Zelin E., Kamer I., Kalinski H., Gorodin S., Fishman A., Chajut A., Einat P., Skaliter R., Gudkov A.V., Chumakov P.M., Feinstein E.
    Oncogene 21:6017-6031(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Amygdala.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Hepatoma and Testis.
  4. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain and Muscle.
  7. "PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse."
    Peeters H., Debeer P., Bairoch A., Wilquet V., Huysmans C., Parthoens E., Fryns J.-P., Gewillig M., Nakamura Y., Niikawa N., Van De Ven W., Devriendt K.
    Hum. Genet. 112:573-580(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  8. "Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD."
    Budanov A.V., Sablina A.A., Feinstein E., Koonin E.V., Chumakov P.M.
    Science 304:596-600(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PRDX1, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-125; CYS-314; CYS-399 AND CYS-430.
  9. "p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling."
    Budanov A.V., Karin M.
    Cell 134:451-460(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TSC1; TSC2 AND AMPK, MUTAGENESIS OF CYS-125.
  10. "Sestrin 2 is not a reductase for cysteine sulfinic acid of peroxiredoxins."
    Woo H.A., Bae S.H., Park S., Rhee S.G.
    Antioxid. Redox Signal. 11:739-745(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  13. "Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage."
    Bae S.H., Sung S.H., Oh S.Y., Lim J.M., Lee S.K., Park Y.N., Lee H.E., Kang D., Rhee S.G.
    Cell Metab. 17:73-84(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH KEAP1; RBX1 AND SQSTM1.
  14. "Toward a comprehensive characterization of a human cancer cell phosphoproteome."
    Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., Mohammed S.
    J. Proteome Res. 12:260-271(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Erythroleukemia.
  15. "Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling."
    Peng M., Yin N., Li M.O.
    Cell 159:122-133(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RRAGA; RRAGB; RRAGC AND RRAGD.
  16. "The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1."
    Chantranupong L., Wolfson R.L., Orozco J.M., Saxton R.A., Scaria S.M., Bar-Peled L., Spooner E., Isasa M., Gygi S.P., Sabatini D.M.
    Cell Rep. 9:1-8(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GATOR2 COMPLEX.
  17. "Sestrins inhibit mTORC1 kinase activation through the GATOR complex."
    Parmigiani A., Nourbakhsh A., Ding B., Wang W., Kim Y.C., Akopiants K., Guan K.L., Karin M., Budanov A.V.
    Cell Rep. 9:1281-1291(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GATOR2 COMPLEX.
  18. "Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of p62/sequestosome-1."
    Ro S.H., Semple I.A., Park H., Park H., Park H.W., Kim M., Kim J.S., Lee J.H.
    FEBS J. 281:3816-3827(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SQSTM1 AND ULK1, PHOSPHORYLATION BY ULK1.
  19. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  20. Cited for: FUNCTION, INDUCTION.
  21. Cited for: FUNCTION, INTERACTION WITH GATOR2 COMPLEX, LEUCINE-BINDING, MUTAGENESIS OF SER-190; LEU-261 AND GLU-451.
  22. "Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate functional domains."
    Kim H., An S., Ro S.H., Teixeira F., Jin Park G., Kim C., Cho C.S., Kim J.S., Jakob U., Lee J.H., Cho U.S.
    Nat. Commun. 6:10025-10025(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY, DOMAIN, ACTIVE SITE, MUTAGENESIS OF PRO-87; HIS-113; CYS-125; TYR-127; LEU-128; HIS-132; CYS-204; CYS-214; VAL-258; GLU-259; LEU-261; 262-MET--ARG-264; ARG-264; 336-THR-PHE-337; 340-GLN-ASP-341; LEU-373; ASN-376; ASP-385; SER-387; CYS-399; ASP-406; ASP-407; ASP-409; GLY-411; GLN-415; ARG-419; LYS-422; LYS-426 AND CYS-430.
  23. Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH LEUCINE, FUNCTION, INTERACTION WITH GATOR2 COMPLEX, REGION, MUTAGENESIS OF HIS-86; THR-374; TYR-375; THR-386; ARG-390; 406-ASP-ASP-407; TRP-444 AND GLU-451.

Entry informationi

Entry nameiSESN2_HUMAN
AccessioniPrimary (citable) accession number: P58004
Secondary accession number(s): Q5T7D0, Q96SI5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 27, 2001
Last modified: July 6, 2016
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.