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Protein

Membrane-bound transcription factor site-1 protease

Gene

Mbtps1

Organism
Rattus norvegicus (Rat)
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

  • serine-type endopeptidase activity Source: RGD

GO - Biological processi

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. 5301.
ReactomeiR-RNO-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-RNO-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
Subtilisin/kexin isozyme 1
Short name:
SKI-1
Gene namesi
Name:Mbtps1
Synonyms:S1p, Ski1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 19

Organism-specific databases

RGDi70935. 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_0000027055Add
BLAST
Chaini187 – 1052866Membrane-bound transcription factor site-1 proteasePRO_0000027056Add
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

PaxDbiQ9WTZ3.
PRIDEiQ9WTZ3.

PTM databases

PhosphoSiteiQ9WTZ3.

Expressioni

Tissue specificityi

Widely expressed. In adult rat, highly expressed in anterior pituitary, thyroid and adrenal glands and in liver. In 2-day old rat, detected in developing skin, striated muscles, cardiac muscles, bones, teeth and internal organs. Highly expressed in retina, cerebellum, pituitary, submaxillary, thyroid and adrenal glands, molars, thymus, kidney and intestine.

Gene expression databases

GenevisibleiQ9WTZ3. RN.

Interactioni

Protein-protein interaction databases

BioGridi250155. 1 interaction.
IntActiQ9WTZ3. 1 interaction.
MINTiMINT-6544799.
STRINGi10116.ENSRNOP00000020838.

Structurei

3D structure databases

ProteinModelPortaliQ9WTZ3.
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.
HOGENOMiHOG000030053.
HOVERGENiHBG052421.
InParanoidiQ9WTZ3.
KOiK08653.
OMAiVIFSDWY.
OrthoDBiEOG7TBC1F.

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.

Q9WTZ3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKLVNIWLLL LVVLLCGKKH LGDRLGKKAF EKAPCPSCSH 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 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
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 AETELKNGAE
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 VVFSDWYNTS VMRKVKFYDE NTRQWWMPDT
760 770 780 790 800
GGANVPALNE LLSVWNMGFS DGLYEGEFAL ANHDMYYASG CSIARFPEDG
810 820 830 840 850
VVITQTFKDQ GLEVLKQETA VVDNVPILGL 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 AQQAHPARTP

SV
Length:1,052
Mass (Da):117,462
Last modified:April 16, 2014 - v2
Checksum:i417A6FEE4DEAB2B6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti301 – 3011I → M in AAD27011 (PubMed:9990022).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF094821 mRNA. Translation: AAD27011.1.
AABR06099111 Genomic DNA. No translation available.
CH473972 Genomic DNA. Translation: EDL92670.1.
RefSeqiNP_446021.1. NM_053569.1.
XP_006255785.1. XM_006255723.2.
UniGeneiRn.2362.

Genome annotation databases

EnsembliENSRNOT00000020838; ENSRNOP00000020838; ENSRNOG00000015173.
ENSRNOT00000087886; ENSRNOP00000071317; ENSRNOG00000015173.
GeneIDi89842.
KEGGirno:89842.
UCSCiRGD:70935. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF094821 mRNA. Translation: AAD27011.1.
AABR06099111 Genomic DNA. No translation available.
CH473972 Genomic DNA. Translation: EDL92670.1.
RefSeqiNP_446021.1. NM_053569.1.
XP_006255785.1. XM_006255723.2.
UniGeneiRn.2362.

3D structure databases

ProteinModelPortaliQ9WTZ3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250155. 1 interaction.
IntActiQ9WTZ3. 1 interaction.
MINTiMINT-6544799.
STRINGi10116.ENSRNOP00000020838.

Protein family/group databases

MEROPSiS08.063.

PTM databases

PhosphoSiteiQ9WTZ3.

Proteomic databases

PaxDbiQ9WTZ3.
PRIDEiQ9WTZ3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000020838; ENSRNOP00000020838; ENSRNOG00000015173.
ENSRNOT00000087886; ENSRNOP00000071317; ENSRNOG00000015173.
GeneIDi89842.
KEGGirno:89842.
UCSCiRGD:70935. rat.

Organism-specific databases

CTDi8720.
RGDi70935. Mbtps1.

Phylogenomic databases

eggNOGiKOG4266. Eukaryota.
COG1404. LUCA.
GeneTreeiENSGT00490000043404.
HOGENOMiHOG000030053.
HOVERGENiHBG052421.
InParanoidiQ9WTZ3.
KOiK08653.
OMAiVIFSDWY.
OrthoDBiEOG7TBC1F.

Enzyme and pathway databases

BRENDAi3.4.21.112. 5301.
ReactomeiR-RNO-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-RNO-381033. ATF6-alpha activates chaperones.

Miscellaneous databases

PROiQ9WTZ3.

Gene expression databases

GenevisibleiQ9WTZ3. RN.

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. "Mammalian subtilisin/kexin isozyme SKI-1: a widely expressed proprotein convertase with a unique cleavage specificity and cellular localization."
    Seidah N.G., Mowla S.J., Hamelin J., Mamarbachi A.M., Benjannet S., Toure B.B., Basak A., Munzer J.S., Marcinkiewicz J., Zhong M., Barale J.-C., Lazure C., Murphy R.A., Chretien M., Marcinkiewicz M.
    Proc. Natl. Acad. Sci. U.S.A. 96:1321-1326(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, SUBCELLULAR LOCATION.
    Strain: Sprague-Dawley.
    Tissue: Adrenal gland.
  2. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
    Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
    , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
    Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Brown Norway.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

Entry informationi

Entry nameiMBTP1_RAT
AccessioniPrimary (citable) accession number: Q9WTZ3
Secondary accession number(s): G3V7Z2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: April 16, 2014
Last modified: June 8, 2016
This is version 114 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.