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Protein

Membrane-bound transcription factor site-1 protease

Gene

Mbtps1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine protease that catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs). Other known substrates are BDNF, GNPTAB and ATF6. Cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4. Cleaves known substrates after Arg-Ser-Val-Leu (SERBP-2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu. Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes (By similarity).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.

Cofactori

Ca2+By similarity

Enzyme regulationi

Inhibited by divalent copper and zinc ions, but not by nickel or cobalt. Inhibited by its prosegment, but not smaller fragments thereof (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei218 – 2181Charge relay systemBy similarity
Active sitei249 – 2491Charge relay systemBy similarity
Active sitei414 – 4141Charge relay systemBy similarity

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
  • nerve growth factor processing Source: Reactome
  • proteolysis Source: UniProtKB
  • regulation of transcription factor import into nucleus Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Keywords - Ligandi

Calcium

Enzyme and pathway databases

ReactomeiR-MMU-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-MMU-167060. NGF processing.
R-MMU-381033. ATF6-alpha activates chaperones.

Protein family/group databases

MEROPSiS08.063.

Names & Taxonomyi

Protein namesi
Recommended name:
Membrane-bound transcription factor site-1 protease (EC:3.4.21.112)
Alternative name(s):
Endopeptidase S1P
Sterol-regulated luminal protease
Subtilisin/kexin isozyme 1
Short name:
SKI-1
Gene namesi
Name:Mbtps1
Synonyms:S1p, Ski1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1927235. Mbtps1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini187 – 999813LumenalSequence analysisAdd
BLAST
Transmembranei1000 – 102223HelicalSequence analysisAdd
BLAST
Topological domaini1023 – 105230CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Sequence analysisAdd
BLAST
Propeptidei18 – 186169Sequence analysisPRO_0000027053Add
BLAST
Chaini187 – 1052866Membrane-bound transcription factor site-1 proteasePRO_0000027054Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi148 – 1481N-linked (GlcNAc...)Sequence analysis
Modified residuei168 – 1681PhosphoserineBy similarity
Glycosylationi236 – 2361N-linked (GlcNAc...)Sequence analysis
Glycosylationi305 – 3051N-linked (GlcNAc...)Sequence analysis
Glycosylationi515 – 5151N-linked (GlcNAc...)Sequence analysis
Glycosylationi728 – 7281N-linked (GlcNAc...)Sequence analysis
Glycosylationi939 – 9391N-linked (GlcNAc...)Sequence analysis

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei186 – 1872Cleavage; by autolysisBy similarity

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

MaxQBiQ9WTZ2.
PaxDbiQ9WTZ2.
PRIDEiQ9WTZ2.

PTM databases

iPTMnetiQ9WTZ2.
PhosphoSiteiQ9WTZ2.

Expressioni

Gene expression databases

BgeeiENSMUSG00000031835.
GenevisibleiQ9WTZ2. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000080117.

Structurei

3D structure databases

ProteinModelPortaliQ9WTZ2.
SMRiQ9WTZ2. Positions 53-473.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini214 – 472259Peptidase S8Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1023 – 105028Arg/Lys/Pro-rich (basic)Add
BLAST

Sequence similaritiesi

Belongs to the peptidase S8 family.Curated
Contains 1 peptidase S8 domain.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4266. Eukaryota.
COG1404. LUCA.
GeneTreeiENSGT00490000043404.
HOVERGENiHBG052421.
InParanoidiQ9WTZ2.
KOiK08653.
OMAiVIFSDWY.
OrthoDBiEOG091G02NH.
PhylomeDBiQ9WTZ2.
TreeFamiTF324501.

Family and domain databases

Gene3Di3.40.50.200. 2 hits.
InterProiIPR000209. Peptidase_S8/S53_dom.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 1 hit.
PfamiPF00082. Peptidase_S8. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SUPFAMiSSF52743. SSF52743. 2 hits.
PROSITEiPS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9WTZ2-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:1,052
Mass (Da):117,457
Last modified:November 1, 1999 - v1
Checksum:iFBBD21C18775FD2A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti714 – 7141V → M in AAH57198 (PubMed:15489334).Curated

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.
CCDSiCCDS22707.1.
RefSeqiNP_001161382.1. NM_001167910.1.
NP_062683.3. NM_019709.4.
XP_011246751.1. XM_011248449.1.
XP_011246752.1. XM_011248450.1.
UniGeneiMm.206934.

Genome annotation databases

EnsembliENSMUST00000081381; ENSMUSP00000080117; ENSMUSG00000031835.
ENSMUST00000098362; ENSMUSP00000095965; ENSMUSG00000031835.
GeneIDi56453.
KEGGimmu:56453.
UCSCiuc009nps.2. mouse.

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.
CCDSiCCDS22707.1.
RefSeqiNP_001161382.1. NM_001167910.1.
NP_062683.3. NM_019709.4.
XP_011246751.1. XM_011248449.1.
XP_011246752.1. XM_011248450.1.
UniGeneiMm.206934.

3D structure databases

ProteinModelPortaliQ9WTZ2.
SMRiQ9WTZ2. Positions 53-473.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000080117.

Protein family/group databases

MEROPSiS08.063.

PTM databases

iPTMnetiQ9WTZ2.
PhosphoSiteiQ9WTZ2.

Proteomic databases

MaxQBiQ9WTZ2.
PaxDbiQ9WTZ2.
PRIDEiQ9WTZ2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000081381; ENSMUSP00000080117; ENSMUSG00000031835.
ENSMUST00000098362; ENSMUSP00000095965; ENSMUSG00000031835.
GeneIDi56453.
KEGGimmu:56453.
UCSCiuc009nps.2. mouse.

Organism-specific databases

CTDi8720.
MGIiMGI:1927235. Mbtps1.

Phylogenomic databases

eggNOGiKOG4266. Eukaryota.
COG1404. LUCA.
GeneTreeiENSGT00490000043404.
HOVERGENiHBG052421.
InParanoidiQ9WTZ2.
KOiK08653.
OMAiVIFSDWY.
OrthoDBiEOG091G02NH.
PhylomeDBiQ9WTZ2.
TreeFamiTF324501.

Enzyme and pathway databases

ReactomeiR-MMU-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-MMU-167060. NGF processing.
R-MMU-381033. ATF6-alpha activates chaperones.

Miscellaneous databases

PROiQ9WTZ2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031835.
GenevisibleiQ9WTZ2. MM.

Family and domain databases

Gene3Di3.40.50.200. 2 hits.
InterProiIPR000209. Peptidase_S8/S53_dom.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 1 hit.
PfamiPF00082. Peptidase_S8. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SUPFAMiSSF52743. SSF52743. 2 hits.
PROSITEiPS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMBTP1_MOUSE
AccessioniPrimary (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: September 7, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.