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Protein

Membrane-bound transcription factor site-1 protease

Gene

Mbtps1

Organism
Rattus norvegicus (Rat)
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

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

GO - Molecular functioni

  • serine-type endopeptidase activity Source: RGD

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi3.4.21.112 5301
ReactomeiR-RNO-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-RNO-381033 ATF6 (ATF6-alpha) activates chaperones
R-RNO-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-RNO-8874211 CREB3 factors activate genes
R-RNO-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
Subtilisin/kexin isozyme 1
Short name:
SKI-1
Gene namesi
Name:Mbtps1
Synonyms:S1p, Ski1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 19

Organism-specific databases

RGDi70935 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_000002705518 – 186Sequence analysisAdd BLAST169
ChainiPRO_0000027056187 – 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

PaxDbiQ9WTZ3
PRIDEiQ9WTZ3

PTM databases

PhosphoSitePlusiQ9WTZ3

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

BgeeiENSRNOG00000015173
GenevisibleiQ9WTZ3 RN

Interactioni

Protein-protein interaction databases

BioGridi250155, 1 interactor
IntActiQ9WTZ3, 1 interactor
MINTiQ9WTZ3
STRINGi10116.ENSRNOP00000020838

Structurei

3D structure databases

ProteinModelPortaliQ9WTZ3
SMRiQ9WTZ3
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
HOGENOMiHOG000030053
HOVERGENiHBG052421
InParanoidiQ9WTZ3
KOiK08653
OMAiLPERMEG
OrthoDBiEOG091G02NH

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, 2 hits
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.

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)DescriptionActionsGraphical viewLength
Sequence conflicti301I → M in AAD27011 (PubMed:9990022).Curated1

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_006255723.3
UniGeneiRn.2362

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiMBTP1_RAT
AccessioniPrimary (citable) accession number: Q9WTZ3
Secondary accession number(s): G3V7Z2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: April 16, 2014
Last modified: May 23, 2018
This is version 127 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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