SESN_DROME
ID SESN_DROME Reviewed; 497 AA.
AC Q9W1K5; A8DYN7; Q9I7V1;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Sestrin homolog {ECO:0000305};
DE Short=dSesn {ECO:0000303|PubMed:29123071};
GN Name=Sesn {ECO:0000312|FlyBase:FBgn0034897};
GN ORFNames=CG11299 {ECO:0000312|EMBL:AAF47053.2};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185 AND SER-190, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF CYS-86.
RX PubMed=20203043; DOI=10.1126/science.1182228;
RA Lee J.H., Budanov A.V., Park E.J., Birse R., Kim T.E., Perkins G.A.,
RA Ocorr K., Ellisman M.H., Bodmer R., Bier E., Karin M.;
RT "Sestrin as a feedback inhibitor of TOR that prevents age-related
RT pathologies.";
RL Science 327:1223-1228(2010).
RN [6]
RP FUNCTION.
RX PubMed=29123071; DOI=10.1126/science.aao3265;
RA Gu X., Orozco J.M., Saxton R.A., Condon K.J., Liu G.Y., Krawczyk P.A.,
RA Scaria S.M., Harper J.W., Gygi S.P., Sabatini D.M.;
RT "SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway.";
RL Science 358:813-818(2017).
CC -!- FUNCTION: Functions as a negative feedback regulator of TOR function.
CC {ECO:0000269|PubMed:20203043, ECO:0000269|PubMed:29123071}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y6P5}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9Y6P5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=A, B, C;
CC IsoId=Q9W1K5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9W1K5-2; Sequence=VSP_006065, VSP_006066;
CC Name=3;
CC IsoId=Q9W1K5-3; Sequence=VSP_006067, VSP_006068;
CC -!- TISSUE SPECIFICITY: Highly expressed in muscle-enriched tissues (at
CC protein level). {ECO:0000269|PubMed:20203043}.
CC -!- INDUCTION: Up-regulated by reactive oxygen species/ROS generated, for
CC instance, upon chronic TOR signaling activation.
CC {ECO:0000269|PubMed:20203043}.
CC -!- DISRUPTION PHENOTYPE: Sesn-null flies do not exhibit developmental
CC abnormalities. However, fat bodies from third-instar larvae contain
CC more lipids and adults also contain more triglycerides. Flies heart
CC function is compromised with arrhythmia and decreased heart rate.
CC Skeletal muscle undergo accelerated age-related degeneration.
CC {ECO:0000269|PubMed:20203043}.
CC -!- SIMILARITY: Belongs to the sestrin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AE013599; AAF47053.2; -; Genomic_DNA.
DR EMBL; AE013599; ABV53897.1; -; Genomic_DNA.
DR EMBL; AE013599; ABV53898.1; -; Genomic_DNA.
DR EMBL; AY069626; AAL39771.1; -; mRNA.
DR RefSeq; NP_001097437.1; NM_001103967.2. [Q9W1K5-1]
DR RefSeq; NP_001097438.1; NM_001103968.2. [Q9W1K5-1]
DR RefSeq; NP_611821.1; NM_137977.4. [Q9W1K5-1]
DR AlphaFoldDB; Q9W1K5; -.
DR SMR; Q9W1K5; -.
DR BioGRID; 63351; 16.
DR DIP; DIP-19601N; -.
DR IntAct; Q9W1K5; 6.
DR STRING; 7227.FBpp0071996; -.
DR iPTMnet; Q9W1K5; -.
DR PaxDb; Q9W1K5; -.
DR PRIDE; Q9W1K5; -.
DR DNASU; 37755; -.
DR EnsemblMetazoa; FBtr0072087; FBpp0071996; FBgn0034897. [Q9W1K5-1]
DR EnsemblMetazoa; FBtr0113113; FBpp0112026; FBgn0034897. [Q9W1K5-1]
DR EnsemblMetazoa; FBtr0113114; FBpp0112027; FBgn0034897. [Q9W1K5-1]
DR GeneID; 37755; -.
DR KEGG; dme:Dmel_CG11299; -.
DR UCSC; CG11299-RA; d. melanogaster. [Q9W1K5-1]
DR UCSC; CG11299-RB; d. melanogaster.
DR CTD; 37755; -.
DR FlyBase; FBgn0034897; Sesn.
DR VEuPathDB; VectorBase:FBgn0034897; -.
DR eggNOG; KOG3746; Eukaryota.
DR GeneTree; ENSGT00950000183168; -.
DR InParanoid; Q9W1K5; -.
DR PhylomeDB; Q9W1K5; -.
DR Reactome; R-DME-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-DME-9755511; KEAP1-NFE2L2 pathway.
DR BioGRID-ORCS; 37755; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 37755; -.
DR PRO; PR:Q9W1K5; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0034897; Expressed in arthropod fat body and 11 other tissues.
DR ExpressionAtlas; Q9W1K5; baseline and differential.
DR Genevisible; Q9W1K5; DM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0070728; F:leucine binding; IBA:GO_Central.
DR GO; GO:0016684; F:oxidoreductase activity, acting on peroxide as acceptor; ISS:FlyBase.
DR GO; GO:0000422; P:autophagy of mitochondrion; IMP:FlyBase.
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:0010259; P:multicellular organism aging; IMP:FlyBase.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:FlyBase.
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:2000377; P:regulation of reactive oxygen species metabolic process; IMP:FlyBase.
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; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..497
FT /note="Sestrin homolog"
FT /id="PRO_0000221186"
FT REGION 226..255
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 226..245
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT VAR_SEQ 80..111
FT /note="AAARHQCPYLVKRYEKEFINQGGDSAWLGGLD -> SIFRLLFPTFISLPNW
FT PKTIAIDWANEEHGLL (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_006065"
FT VAR_SEQ 112..497
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_006066"
FT VAR_SEQ 433..437
FT /note="LLVRP -> VRNQL (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_006067"
FT VAR_SEQ 438..497
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_006068"
FT MUTAGEN 86
FT /note="C->S: No effect on cell growth."
FT /evidence="ECO:0000269|PubMed:20203043"
SQ SEQUENCE 497 AA; 55853 MW; 39AC03B8F653CA30 CRC64;
MYYAVDYYAD MGQISQDCFA ATQTGASDFD MDELDDLDQV TQVIGYHPQF HDHFLATQNF
IMKGDGPLPN DYRYYLAIIA AARHQCPYLV KRYEKEFINQ GGDSAWLGGL DFIPAKLRAI
YDINKILAHR PWLLRKEHIE RLTKGKNSWS LSEVVHAMVL LSHFHSLSSF VFSCGLTQKL
DGLSSPKLKS PPAAVAALAP TILITPTSPT EPQKGKPVLA EISLNNANPD YDSQTAASSN
GGAPPDSANA VADGPDATTL NGYLATAQQL PQQHGISVET LMERMKVLSQ KQDECSEAEL
SSRFQKVEQQ TAELAAVTPE AAVGVPTNLS HYVDDANFIY QDFARRGTES INTFRIQDYS
WEDHGYSLVD GLYNDVGIFL DAKFRAAYNL TYCTMGGIKN VDTSKFRRAI WNYIQCIYGI
RHDDYDYGEV NQLLVRPLKM FIKTACCFPE RITTKDYDSV LVELQDSEKV HVNLMIMEAR
NQAELLYALR EIMRYMT
