Sestrin-2 (EC 1.11.1.-) (Hypoxia-induced gene)
1_MIVAD 6_ SECRA 11_ ELKDY 16_ LRFAP 21_ GGVGD 26_ SGPGE 31_ EQRES 36_ RARRG 41_ PRGPS 46_ AFIPV 51_ EEVLR 56_ EGAES 61_ LEQHL 66_ GLEAL 71_ MSSGR 76_ VDNLA 81_ VVMGL 86_ HPDYF 91_ TSFWR 96_ LHYLL 101_ LHTDG 106_ PLASS 111_ WRHYI 116_ AIMAA 121_ ARHQC 126_ SYLVG 131_ SHMAE 136_ FLQTG 141_ GDPEW 146_ LLGLH 151_ RAPEK 156_ LRKLS 161_ EINKL 166_ LAHRP 171_ WLITK 176_ EHIQA 181_ LLKTG 186_ EHTWS 191_ LAELI 196_ QALVL 201_ LTHCH 206_ SLSSF 211_ VFGCG 216_ ILPEG 221_ DADGS 226_ PAPQA 231_ PTPPS 236_ EQSSP 241_ PSRDP 246_ LNNSG 251_ GFESA 256_ RDVEA 261_ LMERM 266_ QQLQE 271_ SLLRD 276_ EGTSQ 281_ EEMES 286_ RFELE 291_ KSESL 296_ LVTPS 301_ ADILE 306_ PSPHP 311_ DMLCF 316_ VEDPT 321_ FGYED 326_ FTRRG 331_ AQAPP 336_ TFRAQ 341_ DYTWE 346_ DHGYS 351_ LIQRL 356_ YPEGG 361_ QLLDE 366_ KFQAA 371_ YSLTY 376_ NTIAM 381_ HSGVD 386_ TSVLR 391_ RAIWN 396_ YIHCV 401_ FGIRY 406_ DDYDY 411_ GEVNQ 416_ LLERN 421_ LKVYI 426_ KTVAC 431_ YPEKT 436_ TRRMY 441_ NLFWR 446_ HFRHS 451_ EKVHV 456_ NLLLL 461_ EARMQ 466_ AALLY 471_ALRAI
1: Functions as an intracellular leucine sensor that negatively regulates the mTORC1 signaling pathway through the GATOR complex (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26586190, PubMed:26612684, PubMed:31586034, PubMed:35114100, PubMed:35831510, PubMed:36528027). In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents mTORC1 signaling (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26586190, PubMed:26612684, PubMed:31586034, PubMed:35114100, PubMed:35831510, PubMed:36528027). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190, PubMed:35114100, PubMed:35831510, PubMed:36528027). 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 mTORC1 (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). Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the 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)