MBTP1_HUMAN
ID MBTP1_HUMAN Reviewed; 1052 AA.
AC Q14703; A8K6V8; Q24JQ2; Q9UF67;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Membrane-bound transcription factor site-1 protease {ECO:0000305};
DE EC=3.4.21.112 {ECO:0000269|PubMed:10644685, ECO:0000269|PubMed:21719679, ECO:0000269|PubMed:34349020};
DE AltName: Full=Endopeptidase S1P {ECO:0000303|PubMed:10944850};
DE AltName: Full=Subtilisin/kexin-isozyme 1 {ECO:0000303|PubMed:10644685};
DE Short=SKI-1 {ECO:0000303|PubMed:10644685};
DE Flags: Precursor;
GN Name=MBTPS1 {ECO:0000312|HGNC:HGNC:15456};
GN Synonyms=KIAA0091 {ECO:0000303|PubMed:7788527},
GN S1P {ECO:0000303|PubMed:10944850}, SKI1 {ECO:0000303|PubMed:10644685};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Myeloid;
RX PubMed=10944850; DOI=10.1007/s100380070029;
RA Nakajima T., Iwaki K., Kodama T., Inazawa J., Emi M.;
RT "Genomic structure and chromosomal mapping of the human site-1 protease
RT (S1P) gene.";
RL J. Hum. Genet. 45:212-217(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=7788527; DOI=10.1093/dnares/2.1.37;
RA Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S.,
RA Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. III. The
RT coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 2:37-43(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 735-1052.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY
RP REGULATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=10644685; DOI=10.1074/jbc.275.4.2349;
RA Toure B.B., Munzer J.S., Basak A., Benjannet S., Rochemont J., Lazure C.,
RA Chretien M., Seidah N.G.;
RT "Biosynthesis and enzymatic characterization of human SKI-1/S1P and the
RT processing of its inhibitory prosegment.";
RL J. Biol. Chem. 275:2349-2358(2000).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=9990022; DOI=10.1073/pnas.96.4.1321;
RA Seidah N.G., Mowla S.J., Hamelin J., Mamarbachi A.M., Benjannet S.,
RA Toure B.B., Basak A., Munzer J.S., Marcinkiewicz J., Zhong M.,
RA Barale J.-C., Lazure C., Murphy R.A., Chretien M., Marcinkiewicz M.;
RT "Mammalian subtilisin/kexin isozyme SKI-1: a widely expressed proprotein
RT convertase with a unique cleavage specificity and cellular localization.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:1321-1326(1999).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-249.
RX PubMed=12782636; DOI=10.1074/jbc.m300923200;
RA Okada T., Haze K., Nadanaka S., Yoshida H., Seidah N.G., Hirano Y.,
RA Sato R., Negishi M., Mori K.;
RT "A serine protease inhibitor prevents endoplasmic reticulum stress-induced
RT cleavage but not transport of the membrane-bound transcription factor
RT ATF6.";
RL J. Biol. Chem. 278:31024-31032(2003).
RN [10]
RP FUNCTION.
RX PubMed=21719679; DOI=10.1126/science.1205677;
RA Marschner K., Kollmann K., Schweizer M., Braulke T., Pohl S.;
RT "A key enzyme in the biogenesis of lysosomes is a protease that regulates
RT cholesterol metabolism.";
RL Science 333:87-90(2011).
RN [11]
RP PHOSPHORYLATION AT SER-168.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [12]
RP FUNCTION, INVOLVEMENT IN SEDKF, MUTAGENESIS OF SER-414, AND VARIANT SEDKF
RP GLY-365.
RX PubMed=30046013; DOI=10.1172/jci.insight.121596;
RA Kondo Y., Fu J., Wang H., Hoover C., McDaniel J.M., Steet R., Patra D.,
RA Song J., Pollard L., Cathey S., Yago T., Wiley G., Macwana S.,
RA Guthridge J., McGee S., Li S., Griffin C., Furukawa K., James J.A.,
RA Ruan C., McEver R.P., Wierenga K.J., Gaffney P.M., Xia L.;
RT "Site-1 protease deficiency causes human skeletal dysplasia due to
RT defective inter-organelle protein trafficking.";
RL JCI Insight 3:0-0(2018).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH FAM20C, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF SER-414.
RX PubMed=34349020; DOI=10.1073/pnas.2100133118;
RA Chen X., Zhang J., Liu P., Wei Y., Wang X., Xiao J., Wang C.C., Wang L.;
RT "Proteolytic processing of secretory pathway kinase Fam20C by site-1
RT protease promotes biomineralization.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
CC -!- FUNCTION: Serine protease that cleaves after hydrophobic or small
CC residues, provided that Arg or Lys is in position P4: known substrates
CC include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and
CC FAM20C (PubMed:10644685, PubMed:12782636, PubMed:21719679,
CC PubMed:34349020). Cleaves substrates after Arg-Ser-Val-Leu (SREBP2),
CC Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide
CC after Arg-Arg-Leu-Leu (PubMed:10644685, PubMed:21719679). Catalyzes the
CC first step in the proteolytic activation of the sterol regulatory
CC element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2
CC (PubMed:12782636). Also mediates the first step in the proteolytic
CC activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6
CC and ATF6B) (PubMed:12782636). Mediates the protein cleavage of GNPTAB
CC into subunit alpha and beta, thereby participating in biogenesis of
CC lysosomes (PubMed:21719679). Cleaves the propeptide from FAM20C which
CC is required for FAM20C secretion from the Golgi apparatus membrane and
CC for enhancement of FAM20C kinase activity, promoting osteoblast
CC differentiation and biomineralization (PubMed:34349020). Involved in
CC the regulation of M6P-dependent Golgi-to-lysosome trafficking of
CC lysosomal enzymes (PubMed:21719679, PubMed:30046013). It is required
CC for the activation of CREB3L2/BBF2H7, a transcriptional activator of
CC MIA3/TANGO and other genes controlling mega vesicle formation
CC (PubMed:30046013). Therefore, it plays a key role in the regulation of
CC mega vesicle-mediated collagen trafficking (PubMed:30046013).
CC {ECO:0000269|PubMed:10644685, ECO:0000269|PubMed:12782636,
CC ECO:0000269|PubMed:21719679, ECO:0000269|PubMed:30046013,
CC ECO:0000269|PubMed:34349020}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Processes precursors containing basic and
CC hydrophobic/aliphatic residues at P4 and P2, respectively, with a
CC relatively relaxed acceptance of amino acids at P1 and P3.;
CC EC=3.4.21.112; Evidence={ECO:0000269|PubMed:10644685,
CC ECO:0000269|PubMed:12782636, ECO:0000269|PubMed:21719679,
CC ECO:0000269|PubMed:34349020};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:10644685};
CC -!- ACTIVITY REGULATION: Inhibited by divalent copper and zinc ions, but
CC not by nickel or cobalt (PubMed:10644685). Inhibited by its prosegment,
CC but not smaller fragments thereof (PubMed:10644685). Inhibited by 4-(2-
CC aminoethyl)benzenesulfonyl fluoride (AEBSF), a serine protease
CC inhibitor (PubMed:12782636). {ECO:0000269|PubMed:10644685,
CC ECO:0000269|PubMed:12782636}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:9990022}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:9990022}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:34349020, ECO:0000269|PubMed:9990022}; Single-pass
CC type I membrane protein {ECO:0000269|PubMed:9990022}. Note=May sort to
CC other organelles, including lysosomal and/or endosomal compartments.
CC {ECO:0000269|PubMed:9990022}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10944850}.
CC -!- INDUCTION: Down-regulated by sterols. {ECO:0000269|PubMed:10944850}.
CC -!- PTM: The 148 kDa zymogen is processed progressively into two membrane-
CC bound 120 and 106 kDa forms in the endoplasmic reticulum, and late into
CC a secreted 98 kDa form (PubMed:10644685). The propeptide is
CC autocatalytically removed through an intramolecular cleavage after Leu-
CC 186. Further cleavage generates 14, 10, and 8 kDa intermediates
CC (PubMed:10644685). {ECO:0000269|PubMed:10644685}.
CC -!- DISEASE: Spondyloepiphyseal dysplasia, Kondo-Fu type (SEDKF)
CC [MIM:618392]: A disorder characterized by severely retarded growth,
CC spondyloepiphyseal dysplasia, reduced bone mineral density, and
CC markedly elevated plasma levels of various lysosomal enzymes.
CC Additional features include pectus carinatum, kyphosis, a waddling
CC gait, brachydactyly and dysmorphic facial features. SEDKF transmission
CC pattern is consistent with autosomal recessive inheritance.
CC {ECO:0000269|PubMed:30046013}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA07653.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D42053; BAA07653.2; ALT_INIT; mRNA.
DR EMBL; AK291773; BAF84462.1; -; mRNA.
DR EMBL; AC040169; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR EMBL; BC114555; AAI14556.1; -; mRNA.
DR EMBL; BC114961; AAI14962.1; -; mRNA.
DR EMBL; AL133583; CAB63727.1; -; mRNA.
DR CCDS; CCDS10941.1; -.
DR PIR; T43492; T43492.
DR RefSeq; NP_003782.1; NM_003791.3.
DR AlphaFoldDB; Q14703; -.
DR SMR; Q14703; -.
DR BioGRID; 114259; 124.
DR IntAct; Q14703; 13.
DR MINT; Q14703; -.
DR STRING; 9606.ENSP00000344223; -.
DR BindingDB; Q14703; -.
DR ChEMBL; CHEMBL5916; -.
DR GuidetoPHARMACOLOGY; 2381; -.
DR MEROPS; S08.063; -.
DR GlyConnect; 1500; 1 N-Linked glycan (1 site).
DR GlyGen; Q14703; 6 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q14703; -.
DR PhosphoSitePlus; Q14703; -.
DR BioMuta; MBTPS1; -.
DR DMDM; 17368466; -.
DR EPD; Q14703; -.
DR jPOST; Q14703; -.
DR MassIVE; Q14703; -.
DR MaxQB; Q14703; -.
DR PaxDb; Q14703; -.
DR PeptideAtlas; Q14703; -.
DR PRIDE; Q14703; -.
DR ProteomicsDB; 60141; -.
DR Antibodypedia; 1735; 133 antibodies from 24 providers.
DR DNASU; 8720; -.
DR Ensembl; ENST00000343411.8; ENSP00000344223.3; ENSG00000140943.18.
DR GeneID; 8720; -.
DR KEGG; hsa:8720; -.
DR MANE-Select; ENST00000343411.8; ENSP00000344223.3; NM_003791.4; NP_003782.1.
DR UCSC; uc002fhi.5; human.
DR CTD; 8720; -.
DR DisGeNET; 8720; -.
DR GeneCards; MBTPS1; -.
DR HGNC; HGNC:15456; MBTPS1.
DR HPA; ENSG00000140943; Low tissue specificity.
DR MalaCards; MBTPS1; -.
DR MIM; 603355; gene.
DR MIM; 618392; phenotype.
DR neXtProt; NX_Q14703; -.
DR OpenTargets; ENSG00000140943; -.
DR PharmGKB; PA30671; -.
DR VEuPathDB; HostDB:ENSG00000140943; -.
DR eggNOG; KOG4266; Eukaryota.
DR GeneTree; ENSGT00490000043404; -.
DR HOGENOM; CLU_004504_1_0_1; -.
DR InParanoid; Q14703; -.
DR OMA; MKFANIW; -.
DR OrthoDB; 340650at2759; -.
DR PhylomeDB; Q14703; -.
DR TreeFam; TF324501; -.
DR BRENDA; 3.4.21.112; 2681.
DR PathwayCommons; Q14703; -.
DR Reactome; R-HSA-1655829; Regulation of cholesterol biosynthesis by SREBP (SREBF).
DR Reactome; R-HSA-381033; ATF6 (ATF6-alpha) activates chaperones.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-8874211; CREB3 factors activate genes.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR Reactome; R-HSA-8963889; Assembly of active LPL and LIPC lipase complexes.
DR SignaLink; Q14703; -.
DR SIGNOR; Q14703; -.
DR BioGRID-ORCS; 8720; 478 hits in 1092 CRISPR screens.
DR ChiTaRS; MBTPS1; human.
DR GenomeRNAi; 8720; -.
DR Pharos; Q14703; Tchem.
DR PRO; PR:Q14703; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q14703; protein.
DR Bgee; ENSG00000140943; Expressed in stromal cell of endometrium and 205 other tissues.
DR ExpressionAtlas; Q14703; baseline and differential.
DR Genevisible; Q14703; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005795; C:Golgi stack; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0036500; P:ATF6-mediated unfolded protein response; TAS:ParkinsonsUK-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; TAS:Reactome.
DR GO; GO:0007040; P:lysosome organization; IMP:UniProtKB.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISS:ParkinsonsUK-UCL.
DR GO; GO:0016485; P:protein processing; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IMP:UniProtKB.
DR GO; GO:0045540; P:regulation of cholesterol biosynthetic process; TAS:Reactome.
DR GO; GO:0060627; P:regulation of vesicle-mediated transport; IMP:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:ParkinsonsUK-UCL.
DR CDD; cd07479; Peptidases_S8_SKI-1_like; 1.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR022398; Peptidase_S8_His-AS.
DR InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR034185; Site-1_peptidase_cat_dom.
DR Pfam; PF00082; Peptidase_S8; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Calcium; Cholesterol metabolism;
KW Direct protein sequencing; Disease variant; Dwarfism;
KW Endoplasmic reticulum; Glycoprotein; Golgi apparatus; Hydrolase;
KW Lipid metabolism; Membrane; Phosphoprotein; Protease; Reference proteome;
KW Serine protease; Signal; Steroid metabolism; Sterol metabolism;
KW Transmembrane; Transmembrane helix; Zymogen.
FT SIGNAL 1..17
FT PROPEP 18..186
FT /id="PRO_0000027051"
FT CHAIN 187..1052
FT /note="Membrane-bound transcription factor site-1 protease"
FT /id="PRO_0000027052"
FT TOPO_DOM 187..998
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 999..1021
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1022..1052
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 190..472
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT REGION 877..899
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1027..1052
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 877..891
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 218
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 249
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 414
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT SITE 186..187
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:10644685"
FT MOD_RES 168
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 305
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 515
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 728
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 939
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 6
FT /note="I -> T (in dbSNP:rs34701895)"
FT /id="VAR_051822"
FT VARIANT 90
FT /note="R -> G (in dbSNP:rs34076105)"
FT /id="VAR_051823"
FT VARIANT 365
FT /note="D -> G (in SEDKF; due to a nucleotide substitution
FT that creates a dominant splice donor site in exon 9; two
FT different type of transcripts are produced, a major non-
FT functional alternatively spliced transcript with a 41-bp
FT deletion of exon 9, loss of S-414 in the catalytic triad
FT and premature truncation and a normally spliced transcript
FT with variant G-365; the transcript with G-365 produces a
FT catalytically active protein but is the less abundant;
FT dbSNP:rs1226321681)"
FT /evidence="ECO:0000269|PubMed:30046013"
FT /id="VAR_082197"
FT MUTAGEN 249
FT /note="H->A: Abolishes serine protease activity."
FT /evidence="ECO:0000269|PubMed:12782636"
FT MUTAGEN 414
FT /note="S->A: Abolishes serine protease activity. Does not
FT promote FAM20C kinase activity."
FT /evidence="ECO:0000269|PubMed:30046013,
FT ECO:0000269|PubMed:34349020"
FT CONFLICT 843
FT /note="L -> Q (in Ref. 3; BAF84462)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1052 AA; 117749 MW; CA6F013588595B45 CRC64;
MKLVNIWLLL LVVLLCGKKH LGDRLEKKSF EKAPCPGCSH LTLKVEFSST VVEYEYIVAF
NGYFTAKARN SFISSALKSS EVDNWRIIPR NNPSSDYPSD FEVIQIKEKQ KAGLLTLEDH
PNIKRVTPQR KVFRSLKYAE SDPTVPCNET RWSQKWQSSR PLRRASLSLG SGFWHATGRH
SSRRLLRAIP RQVAQTLQAD VLWQMGYTGA NVRVAVFDTG LSEKHPHFKN VKERTNWTNE
RTLDDGLGHG TFVAGVIASM RECQGFAPDA ELHIFRVFTN NQVSYTSWFL DAFNYAILKK
IDVLNLSIGG PDFMDHPFVD KVWELTANNV IMVSAIGNDG PLYGTLNNPA DQMDVIGVGG
IDFEDNIARF SSRGMTTWEL PGGYGRMKPD IVTYGAGVRG SGVKGGCRAL SGTSVASPVV
AGAVTLLVST VQKRELVNPA SMKQALIASA RRLPGVNMFE QGHGKLDLLR AYQILNSYKP
QASLSPSYID LTECPYMWPY CSQPIYYGGM PTVVNVTILN GMGVTGRIVD KPDWQPYLPQ
NGDNIEVAFS YSSVLWPWSG YLAISISVTK KAASWEGIAQ GHVMITVASP AETESKNGAE
QTSTVKLPIK VKIIPTPPRS KRVLWDQYHN LRYPPGYFPR DNLRMKNDPL DWNGDHIHTN
FRDMYQHLRS MGYFVEVLGA PFTCFDASQY GTLLMVDSEE EYFPEEIAKL RRDVDNGLSL
VIFSDWYNTS VMRKVKFYDE NTRQWWMPDT GGANIPALNE LLSVWNMGFS DGLYEGEFTL
ANHDMYYASG CSIAKFPEDG VVITQTFKDQ GLEVLKQETA VVENVPILGL YQIPAEGGGR
IVLYGDSNCL DDSHRQKDCF WLLDALLQYT SYGVTPPSLS HSGNRQRPPS GAGSVTPERM
EGNHLHRYSK VLEAHLGDPK PRPLPACPRL SWAKPQPLNE TAPSNLWKHQ KLLSIDLDKV
VLPNFRSNRP QVRPLSPGES GAWDIPGGIM PGRYNQEVGQ TIPVFAFLGA MVVLAFFVVQ
INKAKSRPKR RKPRVKRPQL MQQVHPPKTP SV
