Guanine nucleotide exchange protein SMCR8 (Smith-Magenis syndrome chromosomal region candidate gene 8 protein)
1_MISAP 6_ DVVAF 11_ TKEEE 16_ YEEEP 21_ YNEPA 26_ LPEEY 31_ SVPLF 36_ PFASQ 41_ GANPW 46_ SKLSG 51_ AKFSR 56_ DFILI 61_ SEFSE 66_ QVGPQ 71_ PLLTI 76_ PNDTK 81_ VFGTF 86_ DLNYF 91_ SLRIM 96_ SVDYQ 101_ ASFVG 106_ HPPGS 111_ AYPKL 116_ NFVED 121_ SKVVL 126_ GDSKE 131_ GAFAY 136_ VHHLT 141_ LYDLE 146_ ARGFV 151_ RPFCM 156_ AYISA 161_ DQHKI 166_ MQQFQ 171_ ELSAE 176_ FSRAS 181_ ECLKT 186_ GNRKA 191_ FAGEL 196_ EKKLK 201_ DLDYT 206_ RTVLH 211_ TETEI 216_ QKKAN 221_ DKGFY 226_ SSQAI 231_ EKANE 236_ LASVE 241_ KSIIE 246_ HQDLL 251_ KQIRS 256_ YPHRK 261_ LKGHD 266_ LCPGE 271_ MEHIQ 276_ DQASQ 281_ ASTTS 286_ NPDES 291_ ADTDL 296_ YTCRP 301_ AYTPK 306_ LIKAK 311_ STKCF 316_ DKKLK 321_ TLEEL 326_ CDTEY 331_ FTQTL 336_ AQLSH 341_ IEHMF 346_ RGDLC 351_ YLLTS 356_ QIDRA 361_ LLKQQ 366_ HITNF 371_ LFEDF 376_ VEVDD 381_ RMVEK 386_ QESIP 391_ SKPSQ 396_ DRPPS 401_ SSLEE 406_ CPIPK 411_ VLISV 416_ GSYKS 421_ SVESV 426_ LIKME 431_ QELGD 436_ EEYKE 441_ VEVTE 446_ LSSFD 451_ PQENL 456_ DYLDM 461_ DMKGS 466_ ISSGE 471_ SIEVL 476_ GTEKS 481_ TSVLS 486_ KSDSQ 491_ ASLTV 496_ PLSPQ 501_ VVRSK 506_ AVSHR 511_ TISED 516_ SIEVL 521_ STCPS 526_ EALIP 531_ DDFKA 536_ SYPSA 541_ INEEE 546_ SYPDG 551_ NEGAI 556_ RFQAS 561_ ISPPE 566_ LGETE 571_ EGSIE 576_ NTPSQ 581_ IDSSC 586_ CIGKE 591_ SDGQL 596_ VLPST 601_ PAHTH 606_ SDEDG 611_ VVSSP 616_ PQRHR 621_ QKDQG 626_ FRVDF 631_ SVENA 636_ NPSSR 641_ DNSCE 646_ GFPAY 651_ ELDPS 656_ HLLAS 661_ RDISK 666_ TSLDN 671_ YSDTT 676_ SYVSS 681_ VASTS 686_ SDRIP 691_ SAYPA 696_ GLSSD 701_ RHKKR 706_ AGQNA 711_ LKFIR 716_ QYPFA 721_ HPAIY 726_ SLLSG 731_ RTLVV 736_ LGEDE 741_ AIVRK 746_ LVTAL 751_ AIFVP 756_ SYGCY 761_ AKPVK 766_ HWASS 771_ PLHIM 776_ DFQKW 781_ KLIGL 786_ QRVAS 791_ PAGAG 796_ TLHAL 801_ SRYSR 806_ YTSIL 811_ DLDNK 816_ TLRCP 821_ LYRGT 826_ LVPRL 831_ ADHRT 836_ QIKRG 841_ STYYL 846_ HVQSM 851_ LTQLC 856_ SKAFL 861_ YTFCH 866_ HLHLP 871_ THDKE 876_ TEELV 881_ ASRQM 886_ SFLKL 891_ TLGLV 896_ NEDVR 901_ VVQYL 906_ AELLK 911_ LHYMQ 916_ ESPGT 921_ SHPML 926_ RFDYV 931_PSFLY
1: Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:20562859, PubMed:27103069, PubMed:27193190, PubMed:27559131, PubMed:27617292, PubMed:28195531, PubMed:32303654). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:20562859, PubMed:27103069, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292, PubMed:28195531). As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro (PubMed:32303654). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131, PubMed:28195531). In addition to its activity in the cytoplasm within the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where it associates with chromatin and negatively regulates expression of suppresses ULK1 and WIPI2 genes (PubMed:28195531)