MBTP1_RAT
ID MBTP1_RAT Reviewed; 1052 AA.
AC Q9WTZ3; G3V7Z2;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Membrane-bound transcription factor site-1 protease;
DE EC=3.4.21.112 {ECO:0000269|PubMed:9990022};
DE AltName: Full=Endopeptidase S1P;
DE AltName: Full=Subtilisin/kexin isozyme 1 {ECO:0000303|PubMed:9990022};
DE Short=SKI-1 {ECO:0000303|PubMed:9990022};
DE Flags: Precursor;
GN Name=Mbtps1; Synonyms=S1p, Ski1 {ECO:0000303|PubMed:9990022};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Adrenal gland;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
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. Cleaves substrates after Arg-Ser-Val-Leu (SREBP2), Arg-His-Leu-
CC Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-
CC Arg-Leu-Leu. Catalyzes the first step in the proteolytic activation of
CC the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1
CC and SREBF2/SREBP2. Also mediates the first step in the proteolytic
CC activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6
CC and ATF6B). Mediates the protein cleavage of GNPTAB into subunit alpha
CC and beta, thereby participating in biogenesis of lysosomes. Cleaves the
CC propeptide from FAM20C which is required for FAM20C secretion from the
CC Golgi apparatus membrane and for enhancement of FAM20C kinase activity,
CC promoting osteoblast differentiation and biomineralization. Involved in
CC the regulation of M6P-dependent Golgi-to-lysosome trafficking of
CC lysosomal enzymes. It is required for the activation of CREB3L2/BBF2H7,
CC a transcriptional activator of MIA3/TANGO and other genes controlling
CC mega vesicle formation. Therefore, it plays a key role in the
CC regulation of mega vesicle-mediated collagen trafficking.
CC {ECO:0000250|UniProtKB:Q14703}.
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:9990022};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:Q14703};
CC -!- ACTIVITY REGULATION: Inhibited by divalent copper and zinc ions, but
CC not by nickel or cobalt. Inhibited by its prosegment, but not smaller
CC fragments thereof. Inhibited by 4-(2-aminoethyl)benzenesulfonyl
CC fluoride (AEBSF), a serine protease inhibitor.
CC {ECO:0000250|UniProtKB:Q14703}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q14703}; Single-pass type I membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:9990022};
CC Single-pass type I membrane protein {ECO:0000255}. Note=May sort to
CC other organelles, including lysosomal and/or endosomal compartments.
CC {ECO:0000250|UniProtKB:Q14703}.
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:9990022). In adult rat,
CC highly expressed in anterior pituitary, thyroid and adrenal glands and
CC in liver (PubMed:9990022). In 2-day old rat, detected in developing
CC skin, striated muscles, cardiac muscles, bones, teeth and internal
CC organs (PubMed:9990022). Highly expressed in retina, cerebellum,
CC pituitary, submaxillary, thyroid and adrenal glands, molars, thymus,
CC kidney and intestine (PubMed:9990022). {ECO:0000269|PubMed:9990022}.
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. The propeptide is autocatalytically removed
CC through an intramolecular cleavage after Leu-186. Further cleavage
CC generates 14, 10, and 8 kDa intermediates.
CC {ECO:0000250|UniProtKB:Q14703}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
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DR EMBL; AF094821; AAD27011.1; -; mRNA.
DR EMBL; AABR06099111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473972; EDL92670.1; -; Genomic_DNA.
DR RefSeq; NP_446021.1; NM_053569.1.
DR RefSeq; XP_006255785.1; XM_006255723.3.
DR AlphaFoldDB; Q9WTZ3; -.
DR SMR; Q9WTZ3; -.
DR BioGRID; 250155; 1.
DR IntAct; Q9WTZ3; 1.
DR MINT; Q9WTZ3; -.
DR STRING; 10116.ENSRNOP00000020838; -.
DR MEROPS; S08.063; -.
DR GlyGen; Q9WTZ3; 6 sites.
DR PhosphoSitePlus; Q9WTZ3; -.
DR PaxDb; Q9WTZ3; -.
DR Ensembl; ENSRNOT00000020838; ENSRNOP00000020838; ENSRNOG00000015173.
DR GeneID; 89842; -.
DR KEGG; rno:89842; -.
DR UCSC; RGD:70935; rat.
DR CTD; 8720; -.
DR RGD; 70935; Mbtps1.
DR eggNOG; KOG4266; Eukaryota.
DR GeneTree; ENSGT00490000043404; -.
DR InParanoid; Q9WTZ3; -.
DR OMA; MKFANIW; -.
DR OrthoDB; 340650at2759; -.
DR TreeFam; TF324501; -.
DR BRENDA; 3.4.21.112; 5301.
DR Reactome; R-RNO-1655829; Regulation of cholesterol biosynthesis by SREBP (SREBF).
DR Reactome; R-RNO-381033; ATF6 (ATF6-alpha) activates chaperones.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-8874211; CREB3 factors activate genes.
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:Q9WTZ3; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Proteomes; UP000234681; Chromosome 19.
DR Bgee; ENSRNOG00000015173; Expressed in lung and 19 other tissues.
DR Genevisible; Q9WTZ3; RN.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005795; C:Golgi stack; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006629; P:lipid metabolic process; ISO:RGD.
DR GO; GO:0007040; P:lysosome organization; ISS:UniProtKB.
DR GO; GO:0016485; P:protein processing; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0060627; P:regulation of vesicle-mediated transport; ISO:RGD.
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 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 /evidence="ECO:0000255"
FT PROPEP 18..186
FT /evidence="ECO:0000255"
FT /id="PRO_0000027055"
FT CHAIN 187..1052
FT /note="Membrane-bound transcription factor site-1 protease"
FT /id="PRO_0000027056"
FT TOPO_DOM 187..999
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1000..1022
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1023..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..900
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1026..1052
FT /note="Disordered"
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:0000250|UniProtKB:Q14703"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14703"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 CONFLICT 301
FT /note="I -> M (in Ref. 1; AAD27011)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1052 AA; 117462 MW; 417A6FEE4DEAB2B6 CRC64;
MKLVNIWLLL LVVLLCGKKH LGDRLGKKAF EKAPCPSCSH LTLKVEFSST VVEYEYIVAF
NGYFTAKARN SFISSALKSS EVDNWRIIPR NNPSSDYPSD FEVIQIKEKQ KAGLLTLEDH
PNIKRVTPQR KVFRSLKFAE SDPIVPCNET RWSQKWQSSR PLKRASLSLG SGFWHATGRH
SSRRLLRAIP RQVAQTLQAD VLWQMGYTGA NVRVAVFDTG LSEKHPHFKN VKERTNWTNE
RTLDDGLGHG TFVAGVIASM RECQGFAPDA ELHIFRVFTN NQVSYTSWFL DAFNYAILKK
IDVLNLSIGG PDFMDHPFVD KVWELTANNV IMVSAIGNDG PLYGTLNNPA DQMDVIGVGG
IDFEDNIARF SSRGMTTWEL PGGYGRVKPD IVTYGAGVRG SGVKGGCRAL SGTSVASPVV
AGAVTLLVST VQKRELVNPA SVKQALIASA RRLPGVNMFE QGHGKLDLLR AYQILSSYKP
QASLSPSYID LTECPYMWPY CSQPIYYGGM PTIVNVTILN GMGVTGRIVD KPEWRPYLPQ
NGDNIEVAFS YSSVLWPWSG YLAISISVTK KAASWEGIAQ GHIMITVASP AETELKNGAE
HTSTVKLPIK VKIIPTPPRS KRVLWDQYHN LRYPPGYFPR DNLRMKNDPL DWNGDHVHTN
FRDMYQHLRS MGYFVEVLGA PFTCFDATQY GTLLMVDSEE EYFPEEIAKL RRDVDNGLSL
VVFSDWYNTS VMRKVKFYDE NTRQWWMPDT GGANVPALNE LLSVWNMGFS DGLYEGEFAL
ANHDMYYASG CSIARFPEDG VVITQTFKDQ GLEVLKQETA VVDNVPILGL YQIPAEGGGR
IVLYGDSNCL DDSHRQKDCF WLLDALLQYT SYGVTPPSLS HSGNRQRPPS GAGLAPPERM
EGNHLHRYSK VLEAHLGDPK PRPLPACPHL SWAKPQPLNE TAPSNLWKHQ KLLSIDLDKV
VLPNFRSNRP QVRPLSPGES GAWDIPGGIM PGRYNQEVGQ TIPVFAFLGA MVALAFFVVQ
ISKAKSRPKR RRPRAKRPQL AQQAHPARTP SV
