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Protein

Membrane-bound transcription factor site-1 protease

Gene

Mbtps1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Activity 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)DescriptionActionsGraphical viewLength
Active sitei218Charge relay systemBy similarity1
Active sitei249Charge relay systemBy similarity1
Active sitei414Charge relay systemBy similarity1

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

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processCholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism
LigandCalcium

Enzyme and pathway databases

ReactomeiR-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

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1927235 Mbtps1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini187 – 999LumenalSequence analysisAdd BLAST813
Transmembranei1000 – 1022HelicalSequence analysisAdd BLAST23
Topological domaini1023 – 1052CytoplasmicSequence analysisAdd BLAST30

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
PropeptideiPRO_000002705318 – 186Sequence analysisAdd BLAST169
ChainiPRO_0000027054187 – 1052Membrane-bound transcription factor site-1 proteaseAdd BLAST866

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi148N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei168PhosphoserineBy similarity1
Glycosylationi236N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi305N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi515N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi728N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi939N-linked (GlcNAc...) asparagineSequence analysis1

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)DescriptionActionsGraphical viewLength
Sitei186 – 187Cleavage; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

MaxQBiQ9WTZ2
PaxDbiQ9WTZ2
PRIDEiQ9WTZ2

PTM databases

iPTMnetiQ9WTZ2
PhosphoSitePlusiQ9WTZ2

Expressioni

Gene expression databases

BgeeiENSMUSG00000031835 Expressed in 310 organ(s), highest expression level in cochlea
GenevisibleiQ9WTZ2 MM

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000080117

Structurei

3D structure databases

ProteinModelPortaliQ9WTZ2
SMRiQ9WTZ2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini214 – 472Peptidase S8Add BLAST259

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1023 – 1050Arg/Lys/Pro-rich (basic)Add BLAST28

Sequence similaritiesi

Belongs to the peptidase S8 family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4266 Eukaryota
COG1404 LUCA
GeneTreeiENSGT00490000043404
HOVERGENiHBG052421
InParanoidiQ9WTZ2
KOiK08653
OMAiLPERMEG
OrthoDBiEOG091G02NH
PhylomeDBiQ9WTZ2
TreeFamiTF324501

Family and domain databases

CDDicd07479 Peptidases_S8_SKI-1_like, 1 hit
Gene3Di3.40.50.200, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00082 Peptidase_S8, 1 hit
PRINTSiPR00723 SUBTILISIN
SUPFAMiSSF52743 SSF52743, 1 hit
PROSITEiView protein in PROSITE
PS00137 SUBTILASE_HIS, 1 hit
PS00138 SUBTILASE_SER, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti714V → M in AAH57198 (PubMed:15489334).Curated1

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_011248449.2
XP_011246752.1, XM_011248450.2
UniGeneiMm.206934

Genome annotation databases

EnsembliENSMUST00000081381; ENSMUSP00000080117; ENSMUSG00000031835
ENSMUST00000098362; ENSMUSP00000095965; ENSMUSG00000031835
GeneIDi56453
KEGGimmu:56453
UCSCiuc009nps.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
CCDSiCCDS22707.1
RefSeqiNP_001161382.1, NM_001167910.1
NP_062683.3, NM_019709.4
XP_011246751.1, XM_011248449.2
XP_011246752.1, XM_011248450.2
UniGeneiMm.206934

3D structure databases

ProteinModelPortaliQ9WTZ2
SMRiQ9WTZ2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000080117

Protein family/group databases

MEROPSiS08.063

PTM databases

iPTMnetiQ9WTZ2
PhosphoSitePlusiQ9WTZ2

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
OMAiLPERMEG
OrthoDBiEOG091G02NH
PhylomeDBiQ9WTZ2
TreeFamiTF324501

Enzyme and pathway databases

ReactomeiR-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

PROiPR:Q9WTZ2
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031835 Expressed in 310 organ(s), highest expression level in cochlea
GenevisibleiQ9WTZ2 MM

Family and domain databases

CDDicd07479 Peptidases_S8_SKI-1_like, 1 hit
Gene3Di3.40.50.200, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00082 Peptidase_S8, 1 hit
PRINTSiPR00723 SUBTILISIN
SUPFAMiSSF52743 SSF52743, 1 hit
PROSITEiView protein in PROSITE
PS00137 SUBTILASE_HIS, 1 hit
PS00138 SUBTILASE_SER, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMBTP1_MOUSE
AccessioniPrimary (citable) accession number: Q9WTZ2
Secondary accession number(s): Q6PG67
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: November 1, 1999
Last modified: November 7, 2018
This is version 153 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

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