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Protein

Membrane-bound transcription factor site-1 protease

Gene

MBTPS1

Organism
Homo sapiens (Human)
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

Enzyme regulationi

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

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: UniProtKB

GO - Biological processi

  • ATF6-mediated unfolded protein response Source: ParkinsonsUK-UCL
  • cholesterol metabolic process Source: UniProtKB-KW
  • lysosome organization Source: UniProtKB
  • membrane protein intracellular domain proteolysis Source: ParkinsonsUK-UCL
  • proteolysis Source: UniProtKB
  • regulation of transcription factor import into nucleus Source: Ensembl
  • 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

BioCyciZFISH:HS06777-MONOMER.
BRENDAi3.4.21.112. 2681.
ReactomeiR-HSA-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-HSA-174800. Chylomicron-mediated lipid transport.
R-HSA-381033. ATF6 (ATF6-alpha) activates chaperones.
SignaLinkiQ14703.
SIGNORiQ14703.

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:KIAA0091, S1P, SKI1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:15456. MBTPS1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini187 – 998LumenalSequence analysisAdd BLAST812
Transmembranei999 – 1021HelicalSequence analysisAdd BLAST23
Topological domaini1022 – 1052CytoplasmicSequence analysisAdd BLAST31

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8720.
OpenTargetsiENSG00000140943.
PharmGKBiPA30671.

Chemistry databases

ChEMBLiCHEMBL5916.
GuidetoPHARMACOLOGYi2381.

Polymorphism and mutation databases

BioMutaiMBTPS1.
DMDMi17368466.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Add BLAST17
PropeptideiPRO_000002705118 – 186Add BLAST169
ChainiPRO_0000027052187 – 1052Membrane-bound transcription factor site-1 proteaseAdd BLAST866

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei168Phosphoserine; by FAM20C1 Publication1
Glycosylationi236N-linked (GlcNAc...)Sequence analysis1
Glycosylationi305N-linked (GlcNAc...)Sequence analysis1
Glycosylationi515N-linked (GlcNAc...)Sequence analysis1
Glycosylationi728N-linked (GlcNAc...)Sequence analysis1
Glycosylationi939N-linked (GlcNAc...)Sequence 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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei186 – 187Cleavage; by autolysis2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

EPDiQ14703.
MaxQBiQ14703.
PaxDbiQ14703.
PeptideAtlasiQ14703.
PRIDEiQ14703.

PTM databases

iPTMnetiQ14703.
PhosphoSitePlusiQ14703.

Miscellaneous databases

PMAP-CutDBQ14703.

Expressioni

Tissue specificityi

Widely expressed.

Inductioni

Down-regulated by sterols.

Gene expression databases

BgeeiENSG00000140943.
CleanExiHS_MBTPS1.
ExpressionAtlasiQ14703. baseline and differential.
GenevisibleiQ14703. HS.

Organism-specific databases

HPAiHPA056109.

Interactioni

Protein-protein interaction databases

BioGridi114259. 16 interactors.
IntActiQ14703. 7 interactors.
MINTiMINT-6774172.
STRINGi9606.ENSP00000344223.

Chemistry databases

BindingDBiQ14703.

Structurei

3D structure databases

ProteinModelPortaliQ14703.
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
Contains 1 peptidase S8 domain.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4266. Eukaryota.
COG1404. LUCA.
GeneTreeiENSGT00490000043404.
HOGENOMiHOG000030053.
HOVERGENiHBG052421.
InParanoidiQ14703.
KOiK08653.
OMAiVIFSDWY.
OrthoDBiEOG091G02NH.
PhylomeDBiQ14703.
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.

Q14703-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKLVNIWLLL LVVLLCGKKH LGDRLEKKSF EKAPCPGCSH LTLKVEFSST
60 70 80 90 100
VVEYEYIVAF NGYFTAKARN SFISSALKSS EVDNWRIIPR NNPSSDYPSD
110 120 130 140 150
FEVIQIKEKQ KAGLLTLEDH PNIKRVTPQR KVFRSLKYAE SDPTVPCNET
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 PGGYGRMKPD IVTYGAGVRG
410 420 430 440 450
SGVKGGCRAL SGTSVASPVV AGAVTLLVST VQKRELVNPA SMKQALIASA
460 470 480 490 500
RRLPGVNMFE QGHGKLDLLR AYQILNSYKP QASLSPSYID LTECPYMWPY
510 520 530 540 550
CSQPIYYGGM PTVVNVTILN GMGVTGRIVD KPDWQPYLPQ NGDNIEVAFS
560 570 580 590 600
YSSVLWPWSG YLAISISVTK KAASWEGIAQ GHVMITVASP AETESKNGAE
610 620 630 640 650
QTSTVKLPIK VKIIPTPPRS KRVLWDQYHN LRYPPGYFPR DNLRMKNDPL
660 670 680 690 700
DWNGDHIHTN FRDMYQHLRS MGYFVEVLGA PFTCFDASQY GTLLMVDSEE
710 720 730 740 750
EYFPEEIAKL RRDVDNGLSL VIFSDWYNTS VMRKVKFYDE NTRQWWMPDT
760 770 780 790 800
GGANIPALNE LLSVWNMGFS DGLYEGEFTL ANHDMYYASG CSIAKFPEDG
810 820 830 840 850
VVITQTFKDQ GLEVLKQETA VVENVPILGL YQIPAEGGGR IVLYGDSNCL
860 870 880 890 900
DDSHRQKDCF WLLDALLQYT SYGVTPPSLS HSGNRQRPPS GAGSVTPERM
910 920 930 940 950
EGNHLHRYSK VLEAHLGDPK PRPLPACPRL SWAKPQPLNE TAPSNLWKHQ
960 970 980 990 1000
KLLSIDLDKV VLPNFRSNRP QVRPLSPGES GAWDIPGGIM PGRYNQEVGQ
1010 1020 1030 1040 1050
TIPVFAFLGA MVVLAFFVVQ INKAKSRPKR RKPRVKRPQL MQQVHPPKTP

SV
Length:1,052
Mass (Da):117,749
Last modified:November 1, 1996 - v1
Checksum:iCA6F013588595B45
GO

Sequence cautioni

The sequence BAA07653 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti843L → Q in BAF84462 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0518226I → T.Corresponds to variant rs34701895dbSNPEnsembl.1
Natural variantiVAR_05182390R → G.Corresponds to variant rs34076105dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D42053 mRNA. Translation: BAA07653.2. Different initiation.
AK291773 mRNA. Translation: BAF84462.1.
AC040169 Genomic RNA. No translation available.
BC114555 mRNA. Translation: AAI14556.1.
BC114961 mRNA. Translation: AAI14962.1.
AL133583 mRNA. Translation: CAB63727.1.
CCDSiCCDS10941.1.
PIRiT43492.
RefSeqiNP_003782.1. NM_003791.3.
UniGeneiHs.75890.

Genome annotation databases

EnsembliENST00000343411; ENSP00000344223; ENSG00000140943.
GeneIDi8720.
KEGGihsa:8720.
UCSCiuc002fhi.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D42053 mRNA. Translation: BAA07653.2. Different initiation.
AK291773 mRNA. Translation: BAF84462.1.
AC040169 Genomic RNA. No translation available.
BC114555 mRNA. Translation: AAI14556.1.
BC114961 mRNA. Translation: AAI14962.1.
AL133583 mRNA. Translation: CAB63727.1.
CCDSiCCDS10941.1.
PIRiT43492.
RefSeqiNP_003782.1. NM_003791.3.
UniGeneiHs.75890.

3D structure databases

ProteinModelPortaliQ14703.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114259. 16 interactors.
IntActiQ14703. 7 interactors.
MINTiMINT-6774172.
STRINGi9606.ENSP00000344223.

Chemistry databases

BindingDBiQ14703.
ChEMBLiCHEMBL5916.
GuidetoPHARMACOLOGYi2381.

Protein family/group databases

MEROPSiS08.063.

PTM databases

iPTMnetiQ14703.
PhosphoSitePlusiQ14703.

Polymorphism and mutation databases

BioMutaiMBTPS1.
DMDMi17368466.

Proteomic databases

EPDiQ14703.
MaxQBiQ14703.
PaxDbiQ14703.
PeptideAtlasiQ14703.
PRIDEiQ14703.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000343411; ENSP00000344223; ENSG00000140943.
GeneIDi8720.
KEGGihsa:8720.
UCSCiuc002fhi.5. human.

Organism-specific databases

CTDi8720.
DisGeNETi8720.
GeneCardsiMBTPS1.
HGNCiHGNC:15456. MBTPS1.
HPAiHPA056109.
MIMi603355. gene.
neXtProtiNX_Q14703.
OpenTargetsiENSG00000140943.
PharmGKBiPA30671.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4266. Eukaryota.
COG1404. LUCA.
GeneTreeiENSGT00490000043404.
HOGENOMiHOG000030053.
HOVERGENiHBG052421.
InParanoidiQ14703.
KOiK08653.
OMAiVIFSDWY.
OrthoDBiEOG091G02NH.
PhylomeDBiQ14703.
TreeFamiTF324501.

Enzyme and pathway databases

BioCyciZFISH:HS06777-MONOMER.
BRENDAi3.4.21.112. 2681.
ReactomeiR-HSA-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-HSA-174800. Chylomicron-mediated lipid transport.
R-HSA-381033. ATF6 (ATF6-alpha) activates chaperones.
SignaLinkiQ14703.
SIGNORiQ14703.

Miscellaneous databases

ChiTaRSiMBTPS1. human.
GenomeRNAii8720.
PMAP-CutDBQ14703.
PROiQ14703.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140943.
CleanExiHS_MBTPS1.
ExpressionAtlasiQ14703. baseline and differential.
GenevisibleiQ14703. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q14703
Secondary accession number(s): A8K6V8, Q24JQ2, Q9UF67
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 159 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. 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.