GATOR complex protein NPRL2 (Gene 21 protein) (G21 protein) (Nitrogen permease regulator 2-like protein) (NPR2-like protein) (Tumor suppressor candidate 4)
1_MGSGC 6_ RIECI 11_ FFSEF 16_ HPTLG 21_ PKITY 26_ QVPED 31_ FISRE 36_ LFDTV 41_ QVYII 46_ TKPEL 51_ QNKLI 56_ TVTAM 61_ EKKLI 66_ GCPVC 71_ IEHKK 76_ YSRNA 81_ LLFNL 86_ GFVCD 91_ AQAKT 96_ CALEP 101_ IVKKL 106_ AGYLT 111_ TLELE 116_ SSFVS 121_ MEESK 126_ QKLVP 131_ IMTIL 136_ LEELN 141_ ASGRC 146_ TLPID 151_ ESNTI 156_ HLKVI 161_ EQRPD 166_ PPVAQ 171_ EYDVP 176_ VFTKD 181_ KEDFF 186_ NSQWD 191_ LTTQQ 196_ ILPYI 201_ DGFRH 206_ IQKIS 211_ AEADV 216_ ELNLV 221_ RIAIQ 226_ NLLYY 231_ GVVTL 236_ VSILQ 241_ YSNVY 246_ CPTPK 251_ VQDLV 256_ DDKSL 261_ QEACL 266_ SYVTK 271_ QGHKR 276_ ASLRD 281_ VFQLY 286_ CSLSP 291_ GTTVR 296_ DLIGR 301_ HPQQL 306_ QHVDE 311_ RKLIQ 316_ FGLMK 321_ NLIRR 326_ LQKYP 331_ VRVTR 336_ EEQSH 341_ PARLY 346_ TGCHS 351_ YDEIC 356_ CKTGM 361_ SYHEL 366_ DERLE 371_NDPNI
1: Catalytic component of the GATOR1 complex, a multiprotein complex that functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:23723238, PubMed:29590090, PubMed:35338845, PubMed:38006878). In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling (PubMed:23723238, PubMed:29590090, PubMed:35338845). In the presence of abundant amino acids, the GATOR1 complex is ubiquitinated and inhibited by GATOR2 (PubMed:23723238, PubMed:36528027). Within the GATOR1 complex, NPRL2 constitutes the catalytic subunit that mediates the GTPase activator activity and under methionine-sufficient conditions, the GTPase activator activity is inhibited by PRMT1 through methylation and consequently inducing timely mTORC1 activation (PubMed:27173016, PubMed:30651352, PubMed:35338845)
2: Suppresses Src-dependent tyrosine phosphorylation and activation of PDPK1 and its downstream signaling (PubMed:18616680). Down-regulates PDPK1 kinase activity by interfering with tyrosine phosphorylation at 'Tyr-9', 'Tyr-373' and 'Tyr-376' residues (PubMed:18616680). May act as a tumor suppressor (PubMed:18616680). Suppresses cell growth and enhances sensitivity to various anticancer drugs (PubMed:18616680)