Guanine nucleotide exchange factor C9orf72
1_MSTLC 6_ PPPSP 11_ AVAKT 16_ EIALS 21_ GKSPL 26_ LAATF 31_ AYWDN 36_ ILGPR 41_ VRHIW 46_ APKTE 51_ QVLLS 56_ DGEIT 61_ FLANH 66_ TLNGE 71_ ILRNA 76_ ESGAI 81_ DVKFF 86_ VLSEK 91_ GVIIV 96_ SLIFD 101_ GNWNG 106_ DRSTY 111_ GLSII 116_ LPQTE 121_ LSFYL 126_ PLHRV 131_ CVDRL 136_ THIIR 141_ KGRIW 146_ MHKER 151_ QENVQ 156_ KIILE 161_ GTERM 166_ EDQGQ 171_ SIIPM 176_ LTGEV 181_ IPVME 186_ LLSSM 191_ KSHSV 196_ PEEID 201_ IADTV 206_ LNDDD 211_ IGDSC 216_ HEGFL 221_ LNAIS 226_ SHLQT 231_ CGCSV 236_ VVGSS 241_ AEKVN 246_ KIVRT 251_ LCLFL 256_ TPAER 261_ KCSRL 266_ CEAES 271_ SFKYE 276_ SGLFV 281_ QGLLK 286_ DSTGS 291_ FVLPF 296_ RQVMY 301_ APYPT 306_ THIDV 311_ DVNTV 316_ KQMPP 321_ CHEHI 326_ YNQRR 331_ YMRSE 336_ LTAFW 341_ RATSE 346_ EDMAQ 351_ DTIIY 356_ TDESF 361_ TPDLN 366_ IFQDV 371_ LHRDT 376_ LVKAF 381_ LDQVF 386_ QLKPG 391_ LSLRS 396_ TFLAQ 401_ FLLVL 406_ HRKAL 411_ TLIKY 416_ IEDDT 421_ QKGKK 426_ PFKSL 431_ RNLKI 436_ DLDLT 441_ AEGDL 446_ NIIMA 451_ LAEKI 456_ KPGLH 461_ SFIFG 466_ RPFYT 471_ SVQER 476_DVLMT
1: Acts as a guanine-nucleotide releasing factor (GEF) for Rab GTPases by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP (PubMed:27103069, PubMed:27193190, PubMed:27617292, PubMed:28195531, PubMed:37821429). Acts as a GEF for RAB39A which enables HOPS-mediated autophagosome-lysosome membrane tethering and fusion in mammalian autophagy (PubMed:37821429). Component of the C9orf72-SMCR8 complex where both subunits display GEF activity and that regulates autophagy (PubMed:27103069, PubMed:27193190, PubMed:27617292, PubMed:28195531). As part of the C9orf72-SMCR8-WDR41 (CSW) complex, functions as GEF for RAB8A and RAB39B, thereby promoting autophagosome maturation (PubMed:27103069). As part of the C9orf72-SMCR8 complex, also functions as GTPase activating protein (GAP) for RAB8A and RAB11A in vitro (PubMed:32303654). The C9orf72-SMCR8 complex also acts as a regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and modulating its protein kinase activity (PubMed:27617292). Promotes initiation of autophagy by regulating the RAB1A-dependent trafficking of the ULK1/ATG1 kinase complex to the phagophore which leads to autophagosome formation (PubMed:27334615). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131). Plays a role in endosomal trafficking (PubMed:24549040). May be involved in regulating the maturation of phagosomes to lysosomes (By similarity). Promotes the lysosomal localization and lysosome-mediated degradation of CARM1 which leads to inhibition of starvation-induced lipid metabolism (By similarity). Regulates actin dynamics in motor neurons by inhibiting the GTP-binding activity of ARF6, leading to ARF6 inactivation (PubMed:27723745). This reduces the activity of the LIMK1 and LIMK2 kinases which are responsible for phosphorylation and inactivation of cofilin, leading to CFL1/cofilin activation (PubMed:27723745). Positively regulates axon extension and axon growth cone size in spinal motor neurons (PubMed:27723745). Required for SMCR8 protein expression and localization at pre- and post-synaptic compartments in the forebrain, also regulates protein abundance of RAB3A and GRIA1/GLUR1 in post-synaptic compartments in the forebrain and hippocampus (By similarity). Plays a role within the hematopoietic system in restricting inflammation and the development of autoimmunity (By similarity)
2: Regulates stress granule assembly in response to cellular stress
3: Does not play a role in regulation of stress granule assembly in response to cellular stress