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Protein

Membrane-bound transcription factor site-1 protease

Gene

MBTPS1

Organism
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
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.1 Publication

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

GO - Biological processi

  • cholesterol metabolic process Source: UniProtKB-KW
  • lysosome organization Source: UniProtKB
  • membrane protein intracellular domain proteolysis Source: ParkinsonsUK-UCL
  • proteolysis Source: UniProtKB
  • response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
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

BRENDAi3.4.21.112. 1309.

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
OrganismiCricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Taxonomic identifieri10029 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeCricetulus
Proteomesi
  • UP000001075 Componenti: Unassembled WGS sequence

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi218 – 2181D → N: Loss of activity. 1 Publication
Mutagenesisi249 – 2491H → F: Loss of activity. 1 Publication
Mutagenesisi414 – 4141S → A: Loss of activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Sequence analysisAdd
BLAST
Propeptidei18 – 186169Sequence analysisPRO_0000027049Add
BLAST
Chaini187 – 1052866Membrane-bound transcription factor site-1 proteasePRO_0000027050Add
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

Expressioni

Inductioni

Down-regulated by sterols.

Structurei

3D structure databases

ProteinModelPortaliQ9Z2A8.
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

HOVERGENiHBG052421.
KOiK08653.

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.

Q9Z2A8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKLINIWLLL LVVLLCGKKH LGDRLGKKAF EKASCPSCSH LTLKVEFSST
60 70 80 90 100
VVEYEYIVAF NGYFTAKARN SFISSALKSS EVDNWRIIPR NNPSSDYPSD
110 120 130 140 150
FEVIQIKEKQ KAGLLTLEDH PNIKRVTPQR KVFRSLKFAE SDPIVPCNET
160 170 180 190 200
RWSQKWQSSR PLRRASLSLG 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
IDVLNLSIGG 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 AETEAKNGAE
610 620 630 640 650
HTSTVKLPIK VKIIPTPPRS KRVLWDQYHN LRYPPGYFPR DNLRMKNDPL
660 670 680 690 700
DWNGDHVHTN FRDMYQHLRS MGYFVEVLGA PFTCFDATQY GTLLMVDSEE
710 720 730 740 750
EYFPEEIAKL RRDVDNGLSL VIFSDWYNTS VMRKVKFYDE NTRQWWMPDT
760 770 780 790 800
GGANIPALNE LLSVWNMGFS DGLYEGEFAL ANHDMYYASG CSIAKFPEDG
810 820 830 840 850
VVITQTFKDQ GLEVLKQETA VVENVPILGL YQIPAEGGGR 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 TQQTHPPRTP

SV
Length:1,052
Mass (Da):117,552
Last modified:April 16, 2014 - v2
Checksum:i7DD079393815BAED
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti875 – 8751T → N in AAC78321 (PubMed:9809072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF078105 mRNA. Translation: AAC78321.1.
JH000004 Genomic DNA. Translation: EGV94126.1.
PIRiT17093.
RefSeqiNP_001233611.1. NM_001246682.1.

Genome annotation databases

GeneIDi100689417.
KEGGicge:100689417.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF078105 mRNA. Translation: AAC78321.1.
JH000004 Genomic DNA. Translation: EGV94126.1.
PIRiT17093.
RefSeqiNP_001233611.1. NM_001246682.1.

3D structure databases

ProteinModelPortaliQ9Z2A8.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiS08.063.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100689417.
KEGGicge:100689417.

Organism-specific databases

CTDi8720.

Phylogenomic databases

HOVERGENiHBG052421.
KOiK08653.

Enzyme and pathway databases

BRENDAi3.4.21.112. 1309.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid composition of animal cells."
    Sakai J., Rawson R.B., Espenshade P.J., Cheng D., Seegmiller A.C., Goldstein J.L., Brown M.S.
    Mol. Cell 2:505-514(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF ASP-218; HIS-249 AND SER-414.
    Tissue: Ovary.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs."
    Ye J., Rawson R.B., Komuro R., Chen X., Dave U.P., Prywes R., Brown M.S., Goldstein J.L.
    Mol. Cell 6:1355-1364(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiMBTP1_CRIGR
AccessioniPrimary (citable) accession number: Q9Z2A8
Secondary accession number(s): G3GRY2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: April 16, 2014
Last modified: September 16, 2015
This is version 86 of the entry and version 2 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. Peptidase families
    Classification of peptidase families and list of entries
  2. 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.