Membrane-bound transcription factor site-1 protease (EC 3.4.21.112) (Endopeptidase S1P) (Subtilisin/kexin-isozyme 1) (SKI-1)
1_MKLVN 6_ IWLLL 11_ LVVLL 16_ CGKKH 21_ LGDRL 26_ EKKSF 31_ EKAPC 36_ PGCSH 41_ LTLKV 46_ EFSST 51_ VVEYE 56_ YIVAF 61_ NGYFT 66_ AKARN 71_ SFISS 76_ ALKSS 81_ EVDNW 86_ RIIPR 91_ NNPSS 96_ DYPSD 101_ FEVIQ 106_ IKEKQ 111_ KAGLL 116_ TLEDH 121_ PNIKR 126_ VTPQR 131_ KVFRS 136_ LKYAE 141_ SDPTV 146_ PCNET 151_ RWSQK 156_ WQSSR 161_ PLRRA 166_ SLSLG 171_ SGFWH 176_ ATGRH 181_ SSRRL 186_ LRAIP 191_ RQVAQ 196_ TLQAD 201_ VLWQM 206_ GYTGA 211_ NVRVA 216_ VFDTG 221_ LSEKH 226_ PHFKN 231_ VKERT 236_ NWTNE 241_ RTLDD 246_ GLGHG 251_ TFVAG 256_ VIASM 261_ RECQG 266_ FAPDA 271_ ELHIF 276_ RVFTN 281_ NQVSY 286_ TSWFL 291_ DAFNY 296_ AILKK 301_ IDVLN 306_ LSIGG 311_ PDFMD 316_ HPFVD 321_ KVWEL 326_ TANNV 331_ IMVSA 336_ IGNDG 341_ PLYGT 346_ LNNPA 351_ DQMDV 356_ IGVGG 361_ IDFED 366_ NIARF 371_ SSRGM 376_ TTWEL 381_ PGGYG 386_ RMKPD 391_ IVTYG 396_ AGVRG 401_ SGVKG 406_ GCRAL 411_ SGTSV 416_ ASPVV 421_ AGAVT 426_ LLVST 431_ VQKRE 436_ LVNPA 441_ SMKQA 446_ LIASA 451_ RRLPG 456_ VNMFE 461_ QGHGK 466_ LDLLR 471_ AYQIL 476_ NSYKP 481_ QASLS 486_ PSYID 491_ LTECP 496_ YMWPY 501_ CSQPI 506_ YYGGM 511_ PTVVN 516_ VTILN 521_ GMGVT 526_ GRIVD 531_ KPDWQ 536_ PYLPQ 541_ NGDNI 546_ EVAFS 551_ YSSVL 556_ WPWSG 561_ YLAIS 566_ ISVTK 571_ KAASW 576_ EGIAQ 581_ GHVMI 586_ TVASP 591_ AETES 596_ KNGAE 601_ QTSTV 606_ KLPIK 611_ VKIIP 616_ TPPRS 621_ KRVLW 626_ DQYHN 631_ LRYPP 636_ GYFPR 641_ DNLRM 646_ KNDPL 651_ DWNGD 656_ HIHTN 661_ FRDMY 666_ QHLRS 671_ MGYFV 676_ EVLGA 681_ PFTCF 686_ DASQY 691_ GTLLM 696_ VDSEE 701_ EYFPE 706_ EIAKL 711_ RRDVD 716_ NGLSL 721_ VIFSD 726_ WYNTS 731_ VMRKV 736_ KFYDE 741_ NTRQW 746_ WMPDT 751_ GGANI 756_ PALNE 761_ LLSVW 766_ NMGFS 771_ DGLYE 776_ GEFTL 781_ ANHDM 786_ YYASG 791_ CSIAK 796_ FPEDG 801_ VVITQ 806_ TFKDQ 811_ GLEVL 816_ KQETA 821_ VVENV 826_ PILGL 831_ YQIPA 836_ EGGGR 841_ IVLYG 846_ DSNCL 851_ DDSHR 856_ QKDCF 861_ WLLDA 866_ LLQYT 871_ SYGVT 876_ PPSLS 881_ HSGNR 886_ QRPPS 891_ GAGSV 896_ TPERM 901_ EGNHL 906_ HRYSK 911_ VLEAH 916_ LGDPK 921_ PRPLP 926_ ACPRL 931_ SWAKP 936_ QPLNE 941_ TAPSN 946_ LWKHQ 951_ KLLSI 956_ DLDKV 961_ VLPNF 966_ RSNRP 971_ QVRPL 976_ SPGES 981_ GAWDI 986_ PGGIM 991_ PGRYN 996_ QEVGQ 1001_ TIPVF 1006_ AFLGA 1011_ MVVLA 1016_ FFVVQ 1021_ INKAK 1026_ SRPKR 1031_ RKPRV 1036_ KRPQL 1041_ MQQVH 1046_PPKTP
1: Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20C (PubMed:10644685, PubMed:12782636, PubMed:21719679, PubMed:34349020). Cleaves substrates after Arg-Ser-Val-Leu (SREBP2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu (PubMed:10644685, PubMed:21719679). Catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:12782636). Also mediates the first step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B) (PubMed:12782636). Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes (PubMed:21719679). Cleaves the propeptide from FAM20C which is required for FAM20C secretion from the Golgi apparatus membrane and for enhancement of FAM20C kinase activity, promoting osteoblast differentiation and biomineralization (PubMed:34349020). Involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes (PubMed:21719679, PubMed:30046013). It is required for the activation of CREB3L2/BBF2H7, a transcriptional activator of MIA3/TANGO and other genes controlling mega vesicle formation (PubMed:30046013). Therefore, it plays a key role in the regulation of mega vesicle-mediated collagen trafficking (PubMed:30046013). In astrocytes and osteoblasts, upon DNA damage and ER stress, mediates the first step of the regulated intramembrane proteolytic activation of the transcription factor CREB3L1, leading to the inhibition of cell-cycle progression (PubMed:16417584)