SESN2_HUMAN
ID SESN2_HUMAN Reviewed; 480 AA.
AC P58004; Q5T7D0; Q96SI5;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Sestrin-2 {ECO:0000305};
DE EC=1.11.1.- {ECO:0000305|PubMed:26612684};
DE AltName: Full=Hypoxia-induced gene {ECO:0000303|PubMed:12203114};
GN Name=SESN2 {ECO:0000312|HGNC:HGNC:20746};
GN Synonyms=Hi95 {ECO:0000303|PubMed:12203114},
GN SEST2 {ECO:0000303|PubMed:12607115};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RX PubMed=12203114; DOI=10.1038/sj.onc.1205877;
RA Budanov A.V., Shoshani T., Faerman A., Zelin E., Kamer I., Kalinski H.,
RA Gorodin S., Fishman A., Chajut A., Einat P., Skaliter R., Gudkov A.V.,
RA Chumakov P.M., Feinstein E.;
RT "Identification of a novel stress-responsive gene Hi95 involved in
RT regulation of cell viability.";
RL Oncogene 21:6017-6031(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Amygdala;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hepatoma, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=12607115; DOI=10.1007/s00439-003-0917-5;
RA Peeters H., Debeer P., Bairoch A., Wilquet V., Huysmans C., Parthoens E.,
RA Fryns J.-P., Gewillig M., Nakamura Y., Niikawa N., Van De Ven W.,
RA Devriendt K.;
RT "PA26 is a candidate gene for heterotaxia in humans: identification of a
RT novel PA26-related gene family in human and mouse.";
RL Hum. Genet. 112:573-580(2003).
RN [8]
RP FUNCTION, INTERACTION WITH PRDX1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP CYS-125; CYS-314; CYS-399 AND CYS-430.
RX PubMed=15105503; DOI=10.1126/science.1095569;
RA Budanov A.V., Sablina A.A., Feinstein E., Koonin E.V., Chumakov P.M.;
RT "Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of
RT bacterial AhpD.";
RL Science 304:596-600(2004).
RN [9]
RP FUNCTION, INTERACTION WITH TSC1; TSC2 AND AMPK, AND MUTAGENESIS OF CYS-125.
RX PubMed=18692468; DOI=10.1016/j.cell.2008.06.028;
RA Budanov A.V., Karin M.;
RT "p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR
RT signaling.";
RL Cell 134:451-460(2008).
RN [10]
RP FUNCTION.
RX PubMed=19113821; DOI=10.1089/ars.2008.2360;
RA Woo H.A., Bae S.H., Park S., Rhee S.G.;
RT "Sestrin 2 is not a reductase for cysteine sulfinic acid of
RT peroxiredoxins.";
RL Antioxid. Redox Signal. 11:739-745(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP FUNCTION, AND INTERACTION WITH KEAP1; RBX1 AND SQSTM1.
RX PubMed=23274085; DOI=10.1016/j.cmet.2012.12.002;
RA Bae S.H., Sung S.H., Oh S.Y., Lim J.M., Lee S.K., Park Y.N., Lee H.E.,
RA Kang D., Rhee S.G.;
RT "Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation
RT of Keap1 and prevent oxidative liver damage.";
RL Cell Metab. 17:73-84(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP INTERACTION WITH RRAGA; RRAGB; RRAGC AND RRAGD.
RX PubMed=25259925; DOI=10.1016/j.cell.2014.08.038;
RA Peng M., Yin N., Li M.O.;
RT "Sestrins function as guanine nucleotide dissociation inhibitors for Rag
RT GTPases to control mTORC1 signaling.";
RL Cell 159:122-133(2014).
RN [16]
RP FUNCTION, AND INTERACTION WITH GATOR2 COMPLEX.
RX PubMed=25263562; DOI=10.1016/j.celrep.2014.09.014;
RA Chantranupong L., Wolfson R.L., Orozco J.M., Saxton R.A., Scaria S.M.,
RA Bar-Peled L., Spooner E., Isasa M., Gygi S.P., Sabatini D.M.;
RT "The Sestrins interact with GATOR2 to negatively regulate the amino-acid-
RT sensing pathway upstream of mTORC1.";
RL Cell Rep. 9:1-8(2014).
RN [17]
RP FUNCTION, AND INTERACTION WITH GATOR2 COMPLEX.
RX PubMed=25457612; DOI=10.1016/j.celrep.2014.10.019;
RA Parmigiani A., Nourbakhsh A., Ding B., Wang W., Kim Y.C., Akopiants K.,
RA Guan K.L., Karin M., Budanov A.V.;
RT "Sestrins inhibit mTORC1 kinase activation through the GATOR complex.";
RL Cell Rep. 9:1281-1291(2014).
RN [18]
RP INTERACTION WITH SQSTM1 AND ULK1, AND PHOSPHORYLATION BY ULK1.
RX PubMed=25040165; DOI=10.1111/febs.12905;
RA Ro S.H., Semple I.A., Park H., Park H., Park H.W., Kim M., Kim J.S.,
RA Lee J.H.;
RT "Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of
RT p62/sequestosome-1.";
RL FEBS J. 281:3816-3827(2014).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP FUNCTION, AND INDUCTION.
RX PubMed=24947615; DOI=10.1038/ncomms5233;
RA Park H.W., Park H., Ro S.H., Jang I., Semple I.A., Kim D.N., Kim M.,
RA Nam M., Zhang D., Yin L., Lee J.H.;
RT "Hepatoprotective role of Sestrin2 against chronic ER stress.";
RL Nat. Commun. 5:4233-4233(2014).
RN [21]
RP FUNCTION, INTERACTION WITH GATOR2 COMPLEX, LEUCINE-BINDING, AND MUTAGENESIS
RP OF SER-190; LEU-261 AND GLU-451.
RX PubMed=26449471; DOI=10.1126/science.aab2674;
RA Wolfson R.L., Chantranupong L., Saxton R.A., Shen K., Scaria S.M.,
RA Cantor J.R., Sabatini D.M.;
RT "Sestrin2 is a leucine sensor for the mTORC1 pathway.";
RL Science 351:43-48(2016).
RN [22]
RP FUNCTION, UBIQUITINATION BY RNF186, AND MUTAGENESIS OF LYS-13.
RX PubMed=31586034; DOI=10.1074/jbc.ac119.010671;
RA Lear T.B., Lockwood K.C., Ouyang Y., Evankovich J.W., Larsen M.B., Lin B.,
RA Liu Y., Chen B.B.;
RT "The RING-type E3 ligase RNF186 ubiquitinates Sestrin-2 and thereby
RT controls nutrient sensing.";
RL J. Biol. Chem. 294:16527-16534(2019).
RN [23]
RP FUNCTION, INTERACTION WITH GATOR2 COMPLEX, UBIQUITINATION AT LYS-175, AND
RP MUTAGENESIS OF LYS-175; LEU-261; ARG-390 AND 406-ASP-ASP-407.
RX PubMed=35114100; DOI=10.1016/j.molcel.2022.01.002;
RA Wang D., Xu C., Yang W., Chen J., Ou Y., Guan Y., Guan J., Liu Y.;
RT "E3 ligase RNF167 and deubiquitinase STAMBPL1 modulate mTOR and cancer
RT progression.";
RL Mol. Cell 82:770-784(2022).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP DOMAIN, ACTIVE SITE, AND MUTAGENESIS OF PRO-87; HIS-113; CYS-125; TYR-127;
RP LEU-128; HIS-132; CYS-204; CYS-214; VAL-258; GLU-259; LEU-261;
RP 262-MET--ARG-264; ARG-264; 336-THR-PHE-337; 340-GLN-ASP-341; LEU-373;
RP ASN-376; ASP-385; SER-387; CYS-399; ASP-406; ASP-407; ASP-409; GLY-411;
RP GLN-415; ARG-419; LYS-422; LYS-426 AND CYS-430.
RX PubMed=26612684; DOI=10.1038/ncomms10025;
RA Kim H., An S., Ro S.H., Teixeira F., Jin Park G., Kim C., Cho C.S.,
RA Kim J.S., Jakob U., Lee J.H., Cho U.S.;
RT "Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate
RT functional domains.";
RL Nat. Commun. 6:10025-10025(2015).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH LEUCINE, FUNCTION,
RP INTERACTION WITH GATOR2 COMPLEX, REGION, AND MUTAGENESIS OF HIS-86;
RP THR-374; TYR-375; THR-386; ARG-390; 406-ASP-ASP-407; TRP-444 AND GLU-451.
RX PubMed=26586190; DOI=10.1126/science.aad2087;
RA Saxton R.A., Knockenhauer K.E., Wolfson R.L., Chantranupong L.,
RA Pacold M.E., Wang T., Schwartz T.U., Sabatini D.M.;
RT "Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway.";
RL Science 351:53-58(2016).
CC -!- FUNCTION: Functions as an intracellular leucine sensor that negatively
CC regulates the TORC1 signaling pathway through the GATOR complex
CC (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471,
CC PubMed:26612684, PubMed:26586190, PubMed:31586034, PubMed:35114100). In
CC absence of leucine, binds the GATOR subcomplex GATOR2 and prevents
CC TORC1 signaling (PubMed:18692468, PubMed:25263562, PubMed:25457612,
CC PubMed:26449471, PubMed:26612684, PubMed:26586190, PubMed:31586034,
CC PubMed:35114100). Binding of leucine to SESN2 disrupts its interaction
CC with GATOR2 thereby activating the TORC1 signaling pathway
CC (PubMed:26449471, PubMed:26586190, PubMed:35114100). This stress-
CC inducible metabolic regulator also plays a role in protection against
CC oxidative and genotoxic stresses. May negatively regulate protein
CC translation in response to endoplasmic reticulum stress, via TORC1
CC (PubMed:24947615). May positively regulate the transcription by NFE2L2
CC of genes involved in the response to oxidative stress by facilitating
CC the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085).
CC May also mediate TP53 inhibition of TORC1 signaling upon genotoxic
CC stress (PubMed:18692468). Moreover, may prevent the accumulation of
CC reactive oxygen species (ROS) through the alkylhydroperoxide reductase
CC activity born by the N-terminal domain of the protein
CC (PubMed:26612684). Was originally reported to contribute to oxidative
CC stress resistance by reducing PRDX1 (PubMed:15105503). However, this
CC could not be confirmed (PubMed:19113821). {ECO:0000269|PubMed:15105503,
CC ECO:0000269|PubMed:18692468, ECO:0000269|PubMed:19113821,
CC ECO:0000269|PubMed:23274085, ECO:0000269|PubMed:24947615,
CC ECO:0000269|PubMed:25263562, ECO:0000269|PubMed:25457612,
CC ECO:0000269|PubMed:26449471, ECO:0000269|PubMed:26586190,
CC ECO:0000269|PubMed:26612684, ECO:0000269|PubMed:35114100}.
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:0000269|PubMed:26612684};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67125;
CC Evidence={ECO:0000305|PubMed:26612684};
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 (PubMed:25263562, PubMed:25457612, PubMed:26449471,
CC PubMed:35114100). Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may
CC function as a guanine nucleotide dissociation inhibitor for RRAGs and
CC regulate them (PubMed:25259925). May interact with the TORC2 complex
CC (By similarity). Interacts with KEAP1, RBX1, SQSTM and ULK1; to
CC regulate the degradation of KEAP1 (PubMed:23274085, PubMed:25040165).
CC May also associate with the complex composed of TSC1, TSC2 and the AMP-
CC responsive protein kinase/AMPK to regulate TORC1 signaling
CC (PubMed:18692468). May interact with PRDX1 (PubMed:15105503).
CC {ECO:0000250|UniProtKB:P58043, ECO:0000269|PubMed:15105503,
CC ECO:0000269|PubMed:18692468, ECO:0000269|PubMed:23274085,
CC ECO:0000269|PubMed:25040165, ECO:0000269|PubMed:25259925,
CC ECO:0000269|PubMed:25263562, ECO:0000269|PubMed:25457612,
CC ECO:0000269|PubMed:26449471, ECO:0000269|PubMed:35114100}.
CC -!- INTERACTION:
CC P58004; Q14145: KEAP1; NbExp=3; IntAct=EBI-3939642, EBI-751001;
CC P58004; Q9NXC5: MIOS; NbExp=5; IntAct=EBI-3939642, EBI-2515122;
CC P58004; P62877: RBX1; NbExp=3; IntAct=EBI-3939642, EBI-398523;
CC P58004; Q13501: SQSTM1; NbExp=9; IntAct=EBI-3939642, EBI-307104;
CC P58004; Q96S15: WDR24; NbExp=17; IntAct=EBI-3939642, EBI-746424;
CC P58004; P62878: Rbx1; Xeno; NbExp=3; IntAct=EBI-3939642, EBI-2507414;
CC P58004; O70405: Ulk1; Xeno; NbExp=5; IntAct=EBI-3939642, EBI-8390771;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15105503}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:12607115}.
CC -!- INDUCTION: Up-regulated by hypoxia and DNA damage (PubMed:12203114).
CC Up-regulated by treatments inducing endoplasmic reticulum stress
CC (PubMed:24947615). {ECO:0000269|PubMed:12203114,
CC ECO:0000269|PubMed:24947615}.
CC -!- DOMAIN: The N-terminal domain has an alkylhydroperoxide reductase
CC activity. {ECO:0000269|PubMed:26612684}.
CC -!- DOMAIN: The C-terminal domain mediates interaction with GATOR2 through
CC which it regulates TORC1 signaling. {ECO:0000269|PubMed:26612684}.
CC -!- PTM: Phosphorylated by ULK1 at multiple sites.
CC {ECO:0000269|PubMed:25040165}.
CC -!- PTM: Ubiquitinated at Lys-175 by RNF167 via 'Lys-63'-linked
CC polyubiquitination in response to leucine deprivation: ubiquitination
CC promotes SESN2-interaction with the GATOR2 complex, leading to inhibit
CC the TORC1 signaling pathway (PubMed:35114100). Deubiquitinated at Lys-
CC 175 by STAMBPL1, promoting the TORC1 signaling pathway
CC (PubMed:35114100). Ubiquitinated by RNF186; ubiquitination mediates
CC proteasomal degradation (PubMed:31586034).
CC {ECO:0000269|PubMed:31586034, ECO:0000269|PubMed:35114100}.
CC -!- SIMILARITY: Belongs to the sestrin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB55438.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY123223; AAM92261.1; -; mRNA.
DR EMBL; AL136551; CAB66486.1; -; mRNA.
DR EMBL; AK027896; BAB55438.1; ALT_INIT; mRNA.
DR EMBL; AK025640; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK315710; BAG38070.1; -; mRNA.
DR EMBL; AL353622; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07703.1; -; Genomic_DNA.
DR EMBL; BC013304; AAH13304.1; -; mRNA.
DR EMBL; BC033719; AAH33719.1; -; mRNA.
DR CCDS; CCDS321.1; -.
DR RefSeq; NP_113647.1; NM_031459.4.
DR PDB; 5CUF; X-ray; 3.50 A; A/B/C/D/E=1-480.
DR PDB; 5DJ4; X-ray; 2.70 A; A/B/C/D/E=1-480.
DR PDB; 5T0N; X-ray; 3.00 A; A/B/C/D/E=1-480.
DR PDB; 6N0M; X-ray; 3.30 A; A/B/C/D/E=66-480.
DR PDBsum; 5CUF; -.
DR PDBsum; 5DJ4; -.
DR PDBsum; 5T0N; -.
DR PDBsum; 6N0M; -.
DR AlphaFoldDB; P58004; -.
DR SMR; P58004; -.
DR BioGRID; 123724; 29.
DR DIP; DIP-62044N; -.
DR IntAct; P58004; 20.
DR MINT; P58004; -.
DR STRING; 9606.ENSP00000253063; -.
DR iPTMnet; P58004; -.
DR PhosphoSitePlus; P58004; -.
DR BioMuta; SESN2; -.
DR DMDM; 13633882; -.
DR EPD; P58004; -.
DR jPOST; P58004; -.
DR MassIVE; P58004; -.
DR MaxQB; P58004; -.
DR PaxDb; P58004; -.
DR PeptideAtlas; P58004; -.
DR PRIDE; P58004; -.
DR ProteomicsDB; 57043; -.
DR Antibodypedia; 2971; 271 antibodies from 34 providers.
DR DNASU; 83667; -.
DR Ensembl; ENST00000253063.4; ENSP00000253063.3; ENSG00000130766.5.
DR Ensembl; ENST00000645231.2; ENSP00000496365.1; ENSG00000285069.2.
DR GeneID; 83667; -.
DR KEGG; hsa:83667; -.
DR MANE-Select; ENST00000253063.4; ENSP00000253063.3; NM_031459.5; NP_113647.1.
DR UCSC; uc001bps.4; human.
DR CTD; 83667; -.
DR DisGeNET; 83667; -.
DR GeneCards; SESN2; -.
DR HGNC; HGNC:20746; SESN2.
DR HPA; ENSG00000130766; Low tissue specificity.
DR MIM; 607767; gene.
DR neXtProt; NX_P58004; -.
DR OpenTargets; ENSG00000130766; -.
DR PharmGKB; PA134882791; -.
DR VEuPathDB; HostDB:ENSG00000130766; -.
DR eggNOG; KOG3746; Eukaryota.
DR GeneTree; ENSGT00950000183168; -.
DR HOGENOM; CLU_020429_0_0_1; -.
DR InParanoid; P58004; -.
DR OMA; GSHMTEF; -.
DR OrthoDB; 588598at2759; -.
DR PhylomeDB; P58004; -.
DR TreeFam; TF314230; -.
DR PathwayCommons; P58004; -.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR SignaLink; P58004; -.
DR SIGNOR; P58004; -.
DR BioGRID-ORCS; 83667; 23 hits in 1092 CRISPR screens.
DR ChiTaRS; SESN2; human.
DR GeneWiki; SESN2; -.
DR GenomeRNAi; 83667; -.
DR Pharos; P58004; Tbio.
DR PRO; PR:P58004; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P58004; protein.
DR Bgee; ENSG00000130766; Expressed in lower esophagus mucosa and 97 other tissues.
DR Genevisible; P58004; HS.
DR GO; GO:1990316; C:Atg1/ULK1 kinase complex; IPI:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:InterPro.
DR GO; GO:0031932; C:TORC2 complex; IEA:Ensembl.
DR GO; GO:0005092; F:GDP-dissociation inhibitor activity; IEA:Ensembl.
DR GO; GO:0070728; F:leucine binding; IDA:UniProtKB.
DR GO; GO:0016684; F:oxidoreductase activity, acting on peroxide as acceptor; IDA:UniProtKB.
DR GO; GO:0140311; F:protein sequestering activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB.
DR GO; GO:0032542; F:sulfiredoxin activity; IDA:UniProtKB.
DR GO; GO:0098869; P:cellular oxidant detoxification; IDA:UniProtKB.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IMP:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; IMP:UniProtKB.
DR GO; GO:0071233; P:cellular response to leucine; IMP:UniProtKB.
DR GO; GO:1990253; P:cellular response to leucine starvation; IMP:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0046323; P:glucose import; IEA:Ensembl.
DR GO; GO:0032042; P:mitochondrial DNA metabolic process; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:1902010; P:negative regulation of translation in response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:1904504; P:positive regulation of lipophagy; IEA:Ensembl.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0036091; P:positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IDA:UniProtKB.
DR GO; GO:2000479; P:regulation of cAMP-dependent protein kinase activity; IEA:Ensembl.
DR GO; GO:0006111; P:regulation of gluconeogenesis; IEA:Ensembl.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:1901031; P:regulation of response to reactive oxygen species; IEA:InterPro.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0070328; P:triglyceride homeostasis; IEA:Ensembl.
DR DisProt; DP03004; -.
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 3D-structure; Acetylation; Cytoplasm; Isopeptide bond; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..480
FT /note="Sestrin-2"
FT /id="PRO_0000221181"
FT REGION 20..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 66..239
FT /note="N-terminal domain; mediates the alkylhydroperoxide
FT reductase activity"
FT /evidence="ECO:0000269|PubMed:26612684"
FT REGION 222..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 272..291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 308..480
FT /note="C-terminal domain; mediates TORC1 regulation"
FT /evidence="ECO:0000269|PubMed:26612684"
FT COMPBIAS 275..291
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 125
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000305|PubMed:26612684"
FT BINDING 374..377
FT /ligand="L-leucine"
FT /ligand_id="ChEBI:CHEBI:57427"
FT /evidence="ECO:0000269|PubMed:26586190,
FT ECO:0007744|PDB:5DJ4"
FT BINDING 386
FT /ligand="L-leucine"
FT /ligand_id="ChEBI:CHEBI:57427"
FT /evidence="ECO:0000269|PubMed:26586190,
FT ECO:0007744|PDB:5DJ4"
FT BINDING 451
FT /ligand="L-leucine"
FT /ligand_id="ChEBI:CHEBI:57427"
FT /evidence="ECO:0000269|PubMed:26586190,
FT ECO:0007744|PDB:5DJ4"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT CROSSLNK 175
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:35114100"
FT VARIANT 320
FT /note="T -> A (in dbSNP:rs2274848)"
FT /id="VAR_022101"
FT MUTAGEN 13
FT /note="K->A: About two-fold prolonged half-life in
FT cycloheximide/CHX time course."
FT /evidence="ECO:0000269|PubMed:26586190"
FT MUTAGEN 86
FT /note="H->A: Loss of leucine-binding."
FT /evidence="ECO:0000269|PubMed:26586190"
FT MUTAGEN 87
FT /note="P->S: No effect on the ability to inhibit the TORC1
FT signaling pathway."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 113
FT /note="H->E: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with C-128."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 125
FT /note="C->S: Decreased alkylhydroperoxide reductase
FT activity and loss of the ability to decrease intracellular
FT reactive oxygen species. No effect on interaction with the
FT GATOR2 complex. No effect on inhibition of TOR signaling."
FT /evidence="ECO:0000269|PubMed:15105503,
FT ECO:0000269|PubMed:18692468, ECO:0000269|PubMed:26612684"
FT MUTAGEN 127
FT /note="Y->F: Decreased alkylhydroperoxide reductase
FT activity. No effect on the ability to inhibit the TORC1
FT signaling pathway."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 128
FT /note="L->C: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with E-113."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 132
FT /note="H->A: Decreased alkylhydroperoxide reductase
FT activity. No effect on the ability to inhibit the TORC1
FT signaling pathway."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 175
FT /note="K->A: Abolished 'Lys-63'-linked ubiquitination by
FT RNF167."
FT /evidence="ECO:0000269|PubMed:35114100"
FT MUTAGEN 190
FT /note="S->W: Loss of interaction with GATOR2. No effect on
FT leucine-binding. Unable to mediate leucine-induced
FT inhibition of the TORC1 signaling pathway."
FT /evidence="ECO:0000269|PubMed:26449471"
FT MUTAGEN 204
FT /note="C->S: No effect on alkylhydroperoxide reductase
FT activity. No effect on the ability to inhibit the TORC1
FT signaling pathway."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 214
FT /note="C->S: No effect on alkylhydroperoxide reductase
FT activity."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 258
FT /note="V->R: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with L-259 and R-261."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 259
FT /note="E->L: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with R-258 and R-261."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 261
FT /note="L->A: Decreased leucine-binding. Promotes
FT interaction with RNF167."
FT /evidence="ECO:0000269|PubMed:26449471,
FT ECO:0000269|PubMed:35114100"
FT MUTAGEN 261
FT /note="L->R: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with R-258 and L-259."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 262..264
FT /note="MER->LMM: No effect on the ability to inhibit the
FT TORC1 signaling pathway."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 264
FT /note="R->P: No effect on the ability to inhibit the TORC1
FT signaling pathway."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 314
FT /note="C->S: No effect on ability to decrease intracellular
FT reactive oxygen species."
FT /evidence="ECO:0000269|PubMed:15105503"
FT MUTAGEN 336..337
FT /note="TF->AA: No effect on the ability to inhibit the
FT TORC1 signaling pathway."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 340..341
FT /note="QD->AA: No effect on the ability to inhibit the
FT TORC1 signaling pathway."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 373
FT /note="L->A: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with A-376."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 374
FT /note="T->A: Loss of leucine-binding. Constitutively
FT interacts with the GATOR2 complex."
FT /evidence="ECO:0000269|PubMed:26586190"
FT MUTAGEN 375
FT /note="Y->A: Loss of leucine-binding."
FT /evidence="ECO:0000269|PubMed:26586190"
FT MUTAGEN 376
FT /note="N->A: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with A-373."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 385
FT /note="D->A: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with A-387."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 386
FT /note="T->A: Loss of leucine-binding. Constitutively
FT interacts with the GATOR2 complex."
FT /evidence="ECO:0000269|PubMed:26586190"
FT MUTAGEN 387
FT /note="S->A: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with A-385."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 390
FT /note="R->A: Loss of leucine-binding. Promotes interaction
FT with RNF167. Constitutively interacts with the GATOR2
FT complex."
FT /evidence="ECO:0000269|PubMed:26586190,
FT ECO:0000269|PubMed:35114100"
FT MUTAGEN 399
FT /note="C->S: No effect on alkylhydroperoxide reductase
FT activity. Altered ability to decrease intracellular
FT reactive oxygen species. No effect on the ability to
FT inhibit the TORC1 signaling pathway."
FT /evidence="ECO:0000269|PubMed:15105503,
FT ECO:0000269|PubMed:26612684"
FT MUTAGEN 406..407
FT /note="DD->AA: Loss of interaction with the GATOR2 complex.
FT No effect on leucine-binding."
FT /evidence="ECO:0000269|PubMed:26586190,
FT ECO:0000269|PubMed:35114100"
FT MUTAGEN 406
FT /note="D->A: No effect on alkylhydroperoxide reductase
FT activity. Loss of interaction with the GATOR2 complex.
FT Unable to inhibit the TORC1 signaling pathway."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 407
FT /note="D->A: No effect on alkylhydroperoxide reductase
FT activity. Loss of interaction with the GATOR2 complex.
FT Unable to inhibit the TORC1 signaling pathway."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 409
FT /note="D->A: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with A-411 and A-415."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 411
FT /note="G->A: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with A-409 and A-415."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 415
FT /note="Q->A: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with A-409 and A-411."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 419
FT /note="R->A: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with A-422 and A-426."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 422
FT /note="K->A: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with A-419 and A-426."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 426
FT /note="K->A: No effect on the ability to inhibit the TORC1
FT signaling pathway; when associated with A-419 and A-422."
FT /evidence="ECO:0000269|PubMed:26612684"
FT MUTAGEN 430
FT /note="C->S: No effect on alkylhydroperoxide reductase
FT activity. Altered ability to decrease intracellular
FT reactive oxygen species. No effect on the ability to
FT inhibit the TORC1 signaling pathway."
FT /evidence="ECO:0000269|PubMed:15105503,
FT ECO:0000269|PubMed:26612684"
FT MUTAGEN 444
FT /note="W->E: Loss of leucine-binding."
FT /evidence="ECO:0000269|PubMed:26586190"
FT MUTAGEN 444
FT /note="W->L: Decreased affinity for leucine. Requires
FT increased leucine concentration to dissociate from GATOR2
FT and activate TORC1 signaling."
FT /evidence="ECO:0000269|PubMed:26586190"
FT MUTAGEN 451
FT /note="E->A: Decreased leucine-binding."
FT /evidence="ECO:0000269|PubMed:26449471"
FT MUTAGEN 451
FT /note="E->Q: Loss of leucine-binding. Constitutively
FT interacts with the GATOR2 complex."
FT /evidence="ECO:0000269|PubMed:26586190"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:5DJ4"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 78..83
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 87..102
FT /evidence="ECO:0007829|PDB:5DJ4"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:6N0M"
FT HELIX 109..121
FT /evidence="ECO:0007829|PDB:5DJ4"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 126..138
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 143..147
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 154..157
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 160..168
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 175..182
FT /evidence="ECO:0007829|PDB:5DJ4"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 191..213
FT /evidence="ECO:0007829|PDB:5DJ4"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:5CUF"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 257..270
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 283..292
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:5DJ4"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 339..341
FT /evidence="ECO:0007829|PDB:5DJ4"
FT TURN 344..347
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 348..355
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 357..371
FT /evidence="ECO:0007829|PDB:5DJ4"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:5T0N"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:5T0N"
FT HELIX 387..400
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 411..416
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 419..430
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 432..434
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 437..442
FT /evidence="ECO:0007829|PDB:5DJ4"
FT HELIX 449..479
FT /evidence="ECO:0007829|PDB:5DJ4"
SQ SEQUENCE 480 AA; 54494 MW; 9C13371316D84060 CRC64;
MIVADSECRA ELKDYLRFAP GGVGDSGPGE EQRESRARRG PRGPSAFIPV EEVLREGAES
LEQHLGLEAL MSSGRVDNLA VVMGLHPDYF TSFWRLHYLL LHTDGPLASS WRHYIAIMAA
ARHQCSYLVG SHMAEFLQTG GDPEWLLGLH RAPEKLRKLS EINKLLAHRP WLITKEHIQA
LLKTGEHTWS LAELIQALVL LTHCHSLSSF VFGCGILPEG DADGSPAPQA PTPPSEQSSP
PSRDPLNNSG GFESARDVEA LMERMQQLQE SLLRDEGTSQ EEMESRFELE KSESLLVTPS
ADILEPSPHP DMLCFVEDPT FGYEDFTRRG AQAPPTFRAQ DYTWEDHGYS LIQRLYPEGG
QLLDEKFQAA YSLTYNTIAM HSGVDTSVLR RAIWNYIHCV FGIRYDDYDY GEVNQLLERN
LKVYIKTVAC YPEKTTRRMY NLFWRHFRHS EKVHVNLLLL EARMQAALLY ALRAITRYMT
