UniProtKB - Q9WTZ2 (MBTP1_MOUSE)
Protein
Membrane-bound transcription factor site-1 protease
Gene
Mbtps1
Organism
Mus musculus (Mouse)
Status
Functioni
Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates are SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6 and ATF6B. 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. Catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2. Also mediates the first step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B). Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes. Involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes. It is required for the activation of CREB3L2/BBF2H7, a transcriptional activator of MIA3/TANGO and other genes controlling mega vesicle formation. Therefore, it plays a key role in the regulation of mega vesicle-mediated collagen trafficking.By similarity
Catalytic activityi
- Processes precursors containing basic and hydrophobic/aliphatic residues at P4 and P2, respectively, with a relatively relaxed acceptance of amino acids at P1 and P3.1 Publication EC:3.4.21.112
Cofactori
Ca2+By similarity
Activity regulationi
Inhibited by divalent copper and zinc ions, but not by nickel or cobalt. Inhibited by its prosegment, but not smaller fragments thereof. Inhibited by 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 218 | Charge relay systemPROSITE-ProRule annotation | 1 | |
Active sitei | 249 | Charge relay systemPROSITE-ProRule annotation | 1 | |
Active sitei | 414 | Charge relay systemPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- endopeptidase activity Source: MGI
- serine-type endopeptidase activity Source: MGI
GO - Biological processi
- cholesterol metabolic process Source: UniProtKB-KW
- lipid metabolic process Source: MGI
- lysosome organization Source: UniProtKB
- protein import into nucleus Source: MGI
- proteolysis Source: UniProtKB
- regulation of vesicle-mediated transport Source: MGI
Keywordsi
Molecular function | Hydrolase, Protease, Serine protease |
Biological process | Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism |
Ligand | Calcium |
Enzyme and pathway databases
Reactomei | R-MMU-1655829, Regulation of cholesterol biosynthesis by SREBP (SREBF) R-MMU-381033, ATF6 (ATF6-alpha) activates chaperones R-MMU-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-MMU-8874211, CREB3 factors activate genes R-MMU-8957275, Post-translational protein phosphorylation |
Protein family/group databases
MEROPSi | S08.063 |
Names & Taxonomyi
Protein namesi | Recommended name: Membrane-bound transcription factor site-1 proteaseCurated (EC:3.4.21.1121 Publication)Alternative name(s): Endopeptidase S1P Sterol-regulated luminal protease Subtilisin/kexin isozyme 11 Publication Short name: SKI-11 Publication |
Gene namesi | Name:Mbtps1 Synonyms:S1p, Ski11 Publication |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1927235, Mbtps1 |
Subcellular locationi
Golgi apparatus
- Golgi apparatus membrane 1 Publication; Single-pass type I membrane protein Sequence analysis
Endoplasmic reticulum
- Endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein Sequence analysis
Note: May sort to other organelles, including lysosomal and/or endosomal compartments.By similarity
Endoplasmic reticulum
- endoplasmic reticulum lumen Source: Reactome
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Golgi apparatus
- Golgi apparatus Source: MGI
- Golgi membrane Source: Reactome
- Golgi stack Source: MGI
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 187 – 999 | LumenalSequence analysisAdd BLAST | 813 | |
Transmembranei | 1000 – 1022 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 1023 – 1052 | CytoplasmicSequence analysisAdd BLAST | 30 |
Keywords - Cellular componenti
Endoplasmic reticulum, Golgi apparatus, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 17 | Sequence analysisAdd BLAST | 17 | |
PropeptideiPRO_0000027053 | 18 – 186 | Sequence analysisAdd BLAST | 169 | |
ChainiPRO_0000027054 | 187 – 1052 | Membrane-bound transcription factor site-1 proteaseAdd BLAST | 866 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 148 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 168 | PhosphoserineBy similarity | 1 | |
Glycosylationi | 236 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 305 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 515 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 728 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 939 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
The 148 kDa zymogen is processed progressively into two membrane-bound 120 and 106 kDa forms in the endoplasmic reticulum, and late into a secreted 98 kDa form. The propeptide is autocatalytically removed through an intramolecular cleavage after Leu-186. Further cleavage generates 14, 10, and 8 kDa intermediates.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 186 – 187 | Cleavage; by autolysisBy similarity | 2 |
Keywords - PTMi
Autocatalytic cleavage, Glycoprotein, Phosphoprotein, ZymogenProteomic databases
MaxQBi | Q9WTZ2 |
PaxDbi | Q9WTZ2 |
PRIDEi | Q9WTZ2 |
PTM databases
GlyGeni | Q9WTZ2, 6 sites |
iPTMneti | Q9WTZ2 |
PhosphoSitePlusi | Q9WTZ2 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000031835, Expressed in cochlea and 325 other tissues |
Genevisiblei | Q9WTZ2, MM |
Interactioni
Protein-protein interaction databases
BioGRIDi | 207992, 3 interactors |
STRINGi | 10090.ENSMUSP00000095965 |
Miscellaneous databases
RNActi | Q9WTZ2, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 190 – 472 | Peptidase S8PROSITE-ProRule annotationAdd BLAST | 283 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1023 – 1050 | Arg/Lys/Pro-rich (basic)Add BLAST | 28 |
Sequence similaritiesi
Belongs to the peptidase S8 family.Curated
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4266, Eukaryota |
GeneTreei | ENSGT00490000043404 |
HOGENOMi | CLU_004504_1_0_1 |
InParanoidi | Q9WTZ2 |
OMAi | SQWMVPC |
OrthoDBi | 340650at2759 |
PhylomeDBi | Q9WTZ2 |
TreeFami | TF324501 |
Family and domain databases
CDDi | cd07479, Peptidases_S8_SKI-1_like, 1 hit |
Gene3Di | 3.40.50.200, 1 hit |
InterProi | View protein in InterPro IPR000209, Peptidase_S8/S53_dom IPR036852, Peptidase_S8/S53_dom_sf IPR022398, Peptidase_S8_His-AS IPR023828, Peptidase_S8_Ser-AS IPR015500, Peptidase_S8_subtilisin-rel IPR034185, Site-1_peptidase_cat_dom |
Pfami | View protein in Pfam PF00082, Peptidase_S8, 1 hit |
PRINTSi | PR00723, SUBTILISIN |
SUPFAMi | SSF52743, SSF52743, 1 hit |
PROSITEi | View protein in PROSITE PS51892, SUBTILASE, 1 hit PS00137, SUBTILASE_HIS, 1 hit PS00138, SUBTILASE_SER, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q9WTZ2-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKLVSTWLLV LVVLLCGKRH LGDRLGTRAL EKAPCPSCSH LTLKVEFSST
60 70 80 90 100
VVEYEYIVAF NGYFTAKARN SFISSALKSS EVENWRIIPR NNPSSDYPSD
110 120 130 140 150
FEVIQIKEKQ KAGLLTLEDH PNIKRVTPQR KVFRSLKFAE SNPIVPCNET
160 170 180 190 200
RWSQKWQSSR PLKRASLSLG SGFWHATGRH SSRRLLRAIP RQVAQTLQAD
210 220 230 240 250
VLWQMGYTGA NVRVAVFDTG LSEKHPHFKN VKERTNWTNE RTLDDGLGHG
260 270 280 290 300
TFVAGVIASM RECQGFAPDA ELHIFRVFTN NQVSYTSWFL DAFNYAILKK
310 320 330 340 350
MDVLNLSIGG PDFMDHPFVD KVWELTANNV IMVSAIGNDG PLYGTLNNPA
360 370 380 390 400
DQMDVIGVGG IDFEDNIARF SSRGMTTWEL PGGYGRVKPD IVTYGAGVRG
410 420 430 440 450
SGVKGGCRAL SGTSVASPVV AGAVTLLVST VQKRELVNPA SVKQALIASA
460 470 480 490 500
RRLPGVNMFE QGHGKLDLLR AYQILSSYKP QASLSPSYID LTECPYMWPY
510 520 530 540 550
CSQPIYYGGM PTIVNVTILN GMGVTGRIVD KPEWRPYLPQ NGDNIEVAFS
560 570 580 590 600
YSSVLWPWSG YLAISISVTK KAASWEGIAQ GHIMITVASP AETELHSGAE
610 620 630 640 650
HTSTVKLPIK VKIIPTPPRS KRVLWDQYHN LRYPPGYFPR DNLRMKNDPL
660 670 680 690 700
DWNGDHVHTN FRDMYQHLRS MGYFVEVLGA PFTCFDATQY GTLLLVDSEE
710 720 730 740 750
EYFPEEIAKL RRDVDNGLSL VIFSDWYNTS VMRKVKFYDE NTRQWWMPDT
760 770 780 790 800
GGANIPALNE LLSVWNMGFS DGLYEGEFVL ANHDMYYASG CSIAKFPEDG
810 820 830 840 850
VVITQTFKDQ GLEVLKQETA VVENVPILGL YQIPSEGGGR IVLYGDSNCL
860 870 880 890 900
DDSHRQKDCF WLLDALLQYT SYGVTPPSLS HSGNRQRPPS GAGLAPPERM
910 920 930 940 950
EGNHLHRYSK VLEAHLGDPK PRPLPACPHL SWAKPQPLNE TAPSNLWKHQ
960 970 980 990 1000
KLLSIDLDKV VLPNFRSNRP QVRPLSPGES GAWDIPGGIM PGRYNQEVGQ
1010 1020 1030 1040 1050
TIPVFAFLGA MVALAFFVVQ ISKAKSRPKR RRPRAKRPQL AQQAHPARTP
SV
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 714 | V → M in AAH57198 (PubMed:15489334).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF094820 mRNA Translation: AAD27010.1 AK029048 mRNA Translation: BAC26263.1 BC054837 mRNA Translation: AAH54837.1 BC057198 mRNA Translation: AAH57198.1 |
CCDSi | CCDS22707.1 |
RefSeqi | NP_001161382.1, NM_001167910.1 NP_062683.3, NM_019709.4 XP_011246751.1, XM_011248449.2 XP_011246752.1, XM_011248450.2 |
Genome annotation databases
Ensembli | ENSMUST00000081381; ENSMUSP00000080117; ENSMUSG00000031835 ENSMUST00000098362; ENSMUSP00000095965; ENSMUSG00000031835 |
GeneIDi | 56453 |
KEGGi | mmu:56453 |
UCSCi | uc009nps.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF094820 mRNA Translation: AAD27010.1 AK029048 mRNA Translation: BAC26263.1 BC054837 mRNA Translation: AAH54837.1 BC057198 mRNA Translation: AAH57198.1 |
CCDSi | CCDS22707.1 |
RefSeqi | NP_001161382.1, NM_001167910.1 NP_062683.3, NM_019709.4 XP_011246751.1, XM_011248449.2 XP_011246752.1, XM_011248450.2 |
3D structure databases
SMRi | Q9WTZ2 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 207992, 3 interactors |
STRINGi | 10090.ENSMUSP00000095965 |
Protein family/group databases
MEROPSi | S08.063 |
PTM databases
GlyGeni | Q9WTZ2, 6 sites |
iPTMneti | Q9WTZ2 |
PhosphoSitePlusi | Q9WTZ2 |
Proteomic databases
MaxQBi | Q9WTZ2 |
PaxDbi | Q9WTZ2 |
PRIDEi | Q9WTZ2 |
Protocols and materials databases
Antibodypediai | 1735, 111 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000081381; ENSMUSP00000080117; ENSMUSG00000031835 ENSMUST00000098362; ENSMUSP00000095965; ENSMUSG00000031835 |
GeneIDi | 56453 |
KEGGi | mmu:56453 |
UCSCi | uc009nps.2, mouse |
Organism-specific databases
CTDi | 8720 |
MGIi | MGI:1927235, Mbtps1 |
Phylogenomic databases
eggNOGi | KOG4266, Eukaryota |
GeneTreei | ENSGT00490000043404 |
HOGENOMi | CLU_004504_1_0_1 |
InParanoidi | Q9WTZ2 |
OMAi | SQWMVPC |
OrthoDBi | 340650at2759 |
PhylomeDBi | Q9WTZ2 |
TreeFami | TF324501 |
Enzyme and pathway databases
Reactomei | R-MMU-1655829, Regulation of cholesterol biosynthesis by SREBP (SREBF) R-MMU-381033, ATF6 (ATF6-alpha) activates chaperones R-MMU-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-MMU-8874211, CREB3 factors activate genes R-MMU-8957275, Post-translational protein phosphorylation |
Miscellaneous databases
BioGRID-ORCSi | 56453, 7 hits in 17 CRISPR screens |
ChiTaRSi | Mbtps1, mouse |
PROi | PR:Q9WTZ2 |
RNActi | Q9WTZ2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000031835, Expressed in cochlea and 325 other tissues |
Genevisiblei | Q9WTZ2, MM |
Family and domain databases
CDDi | cd07479, Peptidases_S8_SKI-1_like, 1 hit |
Gene3Di | 3.40.50.200, 1 hit |
InterProi | View protein in InterPro IPR000209, Peptidase_S8/S53_dom IPR036852, Peptidase_S8/S53_dom_sf IPR022398, Peptidase_S8_His-AS IPR023828, Peptidase_S8_Ser-AS IPR015500, Peptidase_S8_subtilisin-rel IPR034185, Site-1_peptidase_cat_dom |
Pfami | View protein in Pfam PF00082, Peptidase_S8, 1 hit |
PRINTSi | PR00723, SUBTILISIN |
SUPFAMi | SSF52743, SSF52743, 1 hit |
PROSITEi | View protein in PROSITE PS51892, SUBTILASE, 1 hit PS00137, SUBTILASE_HIS, 1 hit PS00138, SUBTILASE_SER, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MBTP1_MOUSE | |
Accessioni | Q9WTZ2Primary (citable) accession number: Q9WTZ2 Secondary accession number(s): Q6PG67 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 16, 2001 |
Last sequence update: | November 1, 1999 | |
Last modified: | December 2, 2020 | |
This is version 167 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Peptidase families
Classification of peptidase families and list of entries