Mbtps1

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 key	Position(s)	DescriptionActions	Length
Active siteⁱ	218	Charge relay systemBy similarity	1
Active siteⁱ	249	Charge relay systemBy similarity	1
Active siteⁱ	414	Charge relay systemBy similarity	1

GO - Molecular functionⁱ

endopeptidase activity
Source: MGI
Inferred from direct assayⁱ
- 15938716
serine-type endopeptidase activity
Source: MGI
Inferred from direct assayⁱ
- 9990022

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cholesterol metabolic process Source: UniProtKB-KW
lipid metabolic process
Source: MGI
Inferred from mutant phenotypeⁱ
- 11717426
lysosome organization Source: UniProtKB
protein import into nucleus
Source: MGI
Inferred from direct assayⁱ
- 15938716
proteolysis Source: UniProtKB

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Hydrolase, Protease, Serine protease
Biological process	Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism
Ligand	Calcium

Enzyme and pathway databases

Reactomeⁱ	R-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

Reactomeⁱ

R-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

MEROPS protease database More...MEROPSⁱ	S08.063

MEROPSⁱ

S08.063

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
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 8

Organism-specific databases

MGIⁱ	MGI:1927235 Mbtps1

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	187 – 999	LumenalSequence analysisAdd BLAST	813
Transmembraneⁱ	1000 – 1022	HelicalSequence analysisAdd BLAST	23
Topological domainⁱ	1023 – 1052	CytoplasmicSequence analysisAdd BLAST	30

Keywords - Cellular componentⁱ

Endoplasmic reticulum, Golgi apparatus, Membrane

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Length
Signal peptideⁱ	1 – 17	Sequence analysisAdd BLAST	17
PropeptideⁱPRO_0000027053	18 – 186	Sequence analysisAdd BLAST	169
ChainⁱPRO_0000027054	187 – 1052	Membrane-bound transcription factor site-1 proteaseAdd BLAST	866

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Glycosylationⁱ	148	N-linked (GlcNAc...) asparagineSequence analysis	1
Modified residueⁱ	168	PhosphoserineBy similarity	1
Glycosylationⁱ	236	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	305	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	515	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	728	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	939	N-linked (GlcNAc...) asparagineSequence analysis	1

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 key	Position(s)	DescriptionActions	Graphical view	Length
Siteⁱ	186 – 187	Cleavage; by autolysisBy similarity		2

Keywords - PTMⁱ

Autocatalytic cleavage, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q9WTZ2
PaxDbⁱ	Q9WTZ2
PRIDEⁱ	Q9WTZ2

PTM databases

iPTMnetⁱ	Q9WTZ2
PhosphoSitePlusⁱ	Q9WTZ2

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSMUSG00000031835 Expressed in 310 organ(s), highest expression level in cochlea
Genevisibleⁱ	Q9WTZ2 MM

Interactionⁱ

Protein-protein interaction databases

STRINGⁱ	10090.ENSMUSP00000080117

STRINGⁱ

10090.ENSMUSP00000080117

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q9WTZ2
SMRⁱ	Q9WTZ2
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	214 – 472	Peptidase S8Add BLAST		259

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	1023 – 1050	Arg/Lys/Pro-rich (basic)Add BLAST		28

Sequence similaritiesⁱ

Belongs to the peptidase S8 family.Curated

Keywords - Domainⁱ

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG4266 Eukaryota COG1404 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00490000043404
HOVERGENⁱ	HBG052421
InParanoidⁱ	Q9WTZ2
KEGG Orthology (KO) More...KOⁱ	K08653
OMAⁱ	LPERMEG
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G02NH
PhylomeDBⁱ	Q9WTZ2
TreeFamⁱ	TF324501

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd07479 Peptidases_S8_SKI-1_like, 1 hit
Gene3Dⁱ	3.40.50.200, 1 hit
InterProⁱ	View 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
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00082 Peptidase_S8, 1 hit
PRINTSⁱ	PR00723 SUBTILISIN
SUPFAMⁱ	SSF52743 SSF52743, 1 hit
PROSITEⁱ	View 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]FASTA Add 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 key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	714	V → M in AAH57198 (PubMed:15489334).Curated		1

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS22707.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001161382.1, NM_001167910.1 NP_062683.3, NM_019709.4 XP_011246751.1, XM_011248449.2 XP_011246752.1, XM_011248450.2
UniGeneⁱ	Mm.206934

Genome annotation databases

Ensemblⁱ	ENSMUST00000081381; ENSMUSP00000080117; ENSMUSG00000031835 ENSMUST00000098362; ENSMUSP00000095965; ENSMUSG00000031835
GeneIDⁱ	56453
KEGGⁱ	mmu:56453
UCSC genome browser More...UCSCⁱ	uc009nps.2 mouse

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q9WTZ2	Membrane-bound transcription factor site-1 protease		HUMAN		1052	UniRef90_Q14703
Membrane-bound transcription factor site-1 protease		RAT		1052
Membrane-bound transcription factor site-1 protease		ALLMI		1109
Uncharacterized protein		COLVI		1076
Membrane-bound transcription factor site-1 protease		PYGAD		1063
+246

Protein	Similar proteins		Species	Score	Length	Source
Q9WTZ2	Membrane-bound transcription factor site-1 protease		HUMAN		1052	UniRef50_Q14703
Membrane-bound transcription factor site-1 protease		RAT		1052
Membrane-bound transcription factor site-1 protease		CRIGR		1052
Membrane-bound transcription factor site-1 protease		ALLMI		1109
Uncharacterized protein		COLVI		1076
+374

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
CCDSⁱ	CCDS22707.1
RefSeqⁱ	NP_001161382.1, NM_001167910.1 NP_062683.3, NM_019709.4 XP_011246751.1, XM_011248449.2 XP_011246752.1, XM_011248450.2
UniGeneⁱ	Mm.206934

3D structure databases

ProteinModelPortalⁱ	Q9WTZ2
SMRⁱ	Q9WTZ2
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

STRINGⁱ	10090.ENSMUSP00000080117

STRINGⁱ

10090.ENSMUSP00000080117

Protein family/group databases

MEROPSⁱ	S08.063

MEROPSⁱ

S08.063

PTM databases

iPTMnetⁱ	Q9WTZ2
PhosphoSitePlusⁱ	Q9WTZ2

Proteomic databases

MaxQBⁱ	Q9WTZ2
PaxDbⁱ	Q9WTZ2
PRIDEⁱ	Q9WTZ2

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000081381; ENSMUSP00000080117; ENSMUSG00000031835 ENSMUST00000098362; ENSMUSP00000095965; ENSMUSG00000031835
GeneIDⁱ	56453
KEGGⁱ	mmu:56453
UCSCⁱ	uc009nps.2 mouse

Organism-specific databases

CTDⁱ	8720
MGIⁱ	MGI:1927235 Mbtps1

Phylogenomic databases

eggNOGⁱ	KOG4266 Eukaryota COG1404 LUCA
GeneTreeⁱ	ENSGT00490000043404
HOVERGENⁱ	HBG052421
InParanoidⁱ	Q9WTZ2
KOⁱ	K08653
OMAⁱ	LPERMEG
OrthoDBⁱ	EOG091G02NH
PhylomeDBⁱ	Q9WTZ2
TreeFamⁱ	TF324501

Enzyme and pathway databases

Reactomeⁱ	R-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

Reactomeⁱ

R-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

Protein Ontology More...PROⁱ	PR:Q9WTZ2
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000031835 Expressed in 310 organ(s), highest expression level in cochlea
Genevisibleⁱ	Q9WTZ2 MM

Family and domain databases

CDDⁱ	cd07479 Peptidases_S8_SKI-1_like, 1 hit
Gene3Dⁱ	3.40.50.200, 1 hit
InterProⁱ	View 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
Pfamⁱ	View protein in Pfam PF00082 Peptidase_S8, 1 hit
PRINTSⁱ	PR00723 SUBTILISIN
SUPFAMⁱ	SSF52743 SSF52743, 1 hit
PROSITEⁱ	View protein in PROSITE PS00137 SUBTILASE_HIS, 1 hit PS00138 SUBTILASE_SER, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	MBTP1_MOUSE
Accessionⁱ	Q9WTZ2Primary (citable) accession number: Q9WTZ2 Secondary accession number(s): Q6PG67
Entry historyⁱ	Integrated 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 statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Peptidase families
Classification of peptidase families and list of entries
MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

UniProtKB

UniParc

Help

UniRef

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UniProtKB - Q9WTZ2 (MBTP1_MOUSE)

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Membrane-bound transcription factor site-1 protease

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Endoplasmic reticulum

Golgi apparatus

Endoplasmic reticulum

Golgi apparatus

Other locations

Topology

Keywords - Cellular componenti

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Sites

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Compositional bias

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ