Hamartin (Tuberous sclerosis 1 protein)
1_MAQQA 6_ NVGEL 11_ LAMLD 16_ SPMLG 21_ VRDDV 26_ TAVFK 31_ ENLNS 36_ DRGPM 41_ LVNTL 46_ VDYYL 51_ ETSSQ 56_ PALHI 61_ LTTLQ 66_ EPHDK 71_ HLLDR 76_ INEYV 81_ GKAAT 86_ RLSIL 91_ SLLGH 96_ VIRLQ 101_ PSWKH 106_ KLSQA 111_ PLLPS 116_ LLKCL 121_ KMDTD 126_ VVVLT 131_ TGVLV 136_ LITML 141_ PMIPQ 146_ SGKQH 151_ LLDFF 156_ DIFGR 161_ LSSWC 166_ LKKPG 171_ HVAEV 176_ YLVHL 181_ HASVY 186_ ALFHR 191_ LYGMY 196_ PCNFV 201_ SFLRS 206_ HYSMK 211_ ENLET 216_ FEEVV 221_ KPMME 226_ HVRIH 231_ PELVT 236_ GSKDH 241_ ELDPR 246_ RWKRL 251_ ETHDV 256_ VIECA 261_ KISLD 266_ PTEAS 271_ YEDGY 276_ SVSHQ 281_ ISARF 286_ PHRSA 291_ DVTTS 296_ PYADT 301_ QNSYG 306_ CATST 311_ PYSTS 316_ RLMLL 321_ NMPGQ 326_ LPQTL 331_ SSPST 336_ RLITE 341_ PPQAT 346_ LWSPS 351_ MVCGM 356_ TTPPT 361_ SPGNV 366_ PPDLS 371_ HPYSK 376_ VFGTT 381_ AGGKG 386_ TPLGT 391_ PATSP 396_ PPAPL 401_ CHSDD 406_ YVHIS 411_ LPQAT 416_ VTPPR 421_ KEERM 426_ DSARP 431_ CLHRQ 436_ HHLLN 441_ DRGSE 446_ EPPGS 451_ KGSVT 456_ LSDLP 461_ GFLGD 466_ LASEE 471_ DSIEK 476_ DKEEA 481_ AISRE 486_ LSEIT 491_ TAEAE 496_ PVVPR 501_ GGFDS 506_ PFYRD 511_ SLPGS 516_ QRKTH 521_ SAASS 526_ SQGAS 531_ VNPEP 536_ LHSSL 541_ DKLGP 546_ DTPKQ 551_ AFTPI 556_ DLPCG 561_ SADES 566_ PAGDR 571_ ECQTS 576_ LETSI 581_ FTPSP 586_ CKIPP 591_ PTRVG 596_ FGSGQ 601_ PPPYD 606_ HLFEV 611_ ALPKT 616_ AHHFV 621_ IRKTE 626_ ELLKK 631_ AKGNT 636_ EEDGV 641_ PSTSP 646_ MEVLD 651_ RLIQQ 656_ GADAH 661_ SKELN 666_ KLPLP 671_ SKSVD 676_ WTHFG 681_ GSPPS 686_ DEIRT 691_ LRDQL 696_ LLLHN 701_ QLLYE 706_ RFKRQ 711_ QHALR 716_ NRRLL 721_ RKVIK 726_ AAALE 731_ EHNAA 736_ MKDQL 741_ KLQEK 746_ DIQMW 751_ KVSLQ 756_ KEQAR 761_ YNQLQ 766_ EQRDT 771_ MVTKL 776_ HSQIR 781_ QLQHD 786_ REEFY 791_ NQSQE 796_ LQTKL 801_ EDCRN 806_ MIAEL 811_ RIELK 816_ KANNK 821_ VCHTE 826_ LLLSQ 831_ VSQKL 836_ SNSES 841_ VQQQM 846_ EFLNR 851_ QLLVL 856_ GEVNE 861_ LYLEQ 866_ LQNKH 871_ SDTTK 876_ EVEMM 881_ KAAYR 886_ KELEK 891_ NRSHV 896_ LQQTQ 901_ RLDTS 906_ QKRIL 911_ ELESH 916_ LAKKD 921_ HLLLE 926_ QKKYL 931_ EDVKL 936_ QARGQ 941_ LQAAE 946_ SRYEA 951_ QKRIT 956_ QVFEL 961_ EILDL 966_ YGRLE 971_ KDGLL 976_ KKLEE 981_ EKAEA 986_ AEAAE 991_ ERLDC 996_ CNDGC 1001_ SDSMV 1006_ GHNEE 1011_ ASGHN 1016_ GETKT 1021_ PRPSS 1026_ ARGSS 1031_ GSRGG 1036_ GGSSS 1041_ SSSEL 1046_ STPEK 1051_ PPHQR 1056_ AGPFS 1061_ SRWET 1066_ TMGEA 1071_ SASIP 1076_ TTVGS 1081_ LPSSK 1086_ SFLGM 1091_ KAREL 1096_ FRNKS 1101_ ESQCD 1106_ EDGMT 1111_ SSLSE 1116_ SLKTE 1121_ LGKDL 1126_ GVEAK 1131_ IPLNL 1136_ DGPHP 1141_ SPPTP 1146_ DSVGQ 1151_ LHIMD 1156_YNETH
1: Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12906785, PubMed:15340059, PubMed:24529379, PubMed:28215400). The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12906785, PubMed:15340059, PubMed:24529379). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12271141, PubMed:24529379, PubMed:28215400, PubMed:33215753). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Within the TSC-TBC complex, TSC1 stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:10585443, PubMed:28215400). Acts as a tumor suppressor (PubMed:9242607). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 (PubMed:29127155). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (PubMed:16464865, PubMed:29127155)