Q9WTZ3 · MBTP1_RAT

  • Protein
    Membrane-bound transcription factor site-1 protease
  • Gene
    Mbtps1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20C. Cleaves substrates after Arg-Ser-Val-Leu (SREBP2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu. Catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2. Also mediates the first step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B). Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes. Cleaves the propeptide from FAM20C which is required for FAM20C secretion from the Golgi apparatus membrane and for enhancement of FAM20C kinase activity, promoting osteoblast differentiation and biomineralization. Involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes. It is required for the activation of CREB3L2/BBF2H7, a transcriptional activator of MIA3/TANGO and other genes controlling mega vesicle formation. Therefore, it plays a key role in the regulation of mega vesicle-mediated collagen trafficking. In astrocytes and osteoblasts, upon DNA damage and ER stress, mediates the first step of the regulated intramembrane proteolytic activation of the transcription factor CREB3L1, leading to the inhibition of cell-cycle progression.

Catalytic activity

  • 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.
    EC:3.4.21.112 (UniProtKB | ENZYME | Rhea)

Cofactor

Ca2+ (UniProtKB | Rhea| CHEBI:29108 )

Activity regulation

Inhibited by divalent copper and zinc ions, but not by nickel or cobalt. Inhibited by its prosegment, but not smaller fragments. Inhibited by 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor.

Features

Showing features for site, active site.

TypeIDPosition(s)Description
Site186-187Cleavage; by autolysis
Active site218Charge relay system
Active site249Charge relay system
Active site414Charge relay system

GO annotations

AspectTerm
Cellular Componentendoplasmic reticulum membrane
Cellular ComponentGolgi apparatus
Cellular ComponentGolgi membrane
Cellular ComponentGolgi stack
Molecular Functionserine-type endopeptidase activity
Biological Processcholesterol metabolic process
Biological Processlipid metabolic process
Biological Processlysosome organization
Biological Processmembrane protein intracellular domain proteolysis
Biological Processmitotic G2 DNA damage checkpoint signaling
Biological Processprotein maturation
Biological Processprotein processing
Biological Processproteolysis
Biological Processregulation of vesicle-mediated transport

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Membrane-bound transcription factor site-1 protease
  • EC number
  • Alternative names
    • Endopeptidase S1P
    • Subtilisin/kexin isozyme 1
      (SKI-1
      )

Gene names

    • Name
      Mbtps1
    • Synonyms
      S1p, Ski1

Organism names

  • Taxonomic identifier
  • Strains
    • Sprague-Dawley
    • Brown Norway
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    Q9WTZ3
  • Secondary accessions
    • G3V7Z2

Proteomes

Organism-specific databases

Subcellular Location

Endoplasmic reticulum membrane
; Single-pass type I membrane protein
Golgi apparatus membrane
; Single-pass type I membrane protein
Note: May sort to other organelles, including lysosomal and/or endosomal compartments.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain187-999Lumenal
Transmembrane1000-1022Helical
Topological domain1023-1052Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for signal, propeptide, glycosylation, modified residue, chain.

TypeIDPosition(s)Description
Signal1-17
PropeptidePRO_000002705518-186
Glycosylation148N-linked (GlcNAc...) asparagine
Modified residue168Phosphoserine
ChainPRO_0000027056187-1052Membrane-bound transcription factor site-1 protease
Glycosylation236N-linked (GlcNAc...) asparagine
Glycosylation305N-linked (GlcNAc...) asparagine
Glycosylation515N-linked (GlcNAc...) asparagine
Glycosylation728N-linked (GlcNAc...) asparagine
Glycosylation939N-linked (GlcNAc...) asparagine

Post-translational modification

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.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Widely expressed (PubMed:9990022).
In adult rat, highly expressed in anterior pituitary, thyroid and adrenal glands and in liver (PubMed:9990022).
In 2-day old rat, detected in developing skin, striated muscles, cardiac muscles, bones, teeth and internal organs (PubMed:9990022).
Highly expressed in retina, cerebellum, pituitary, submaxillary, thyroid and adrenal glands, molars, thymus, kidney and intestine (PubMed:9990022).

Gene expression databases

Interaction

Subunit

Interacts with LYSET; this interaction bridges GNPTAB to MBTPS1.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for domain, region.

TypeIDPosition(s)Description
Domain190-472Peptidase S8
Region877-900Disordered
Region1026-1052Disordered

Sequence similarities

Belongs to the peptidase S8 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    1,052
  • Mass (Da)
    117,462
  • Last updated
    2014-04-16 v2
  • Checksum
    417A6FEE4DEAB2B6
MKLVNIWLLLLVVLLCGKKHLGDRLGKKAFEKAPCPSCSHLTLKVEFSSTVVEYEYIVAFNGYFTAKARNSFISSALKSSEVDNWRIIPRNNPSSDYPSDFEVIQIKEKQKAGLLTLEDHPNIKRVTPQRKVFRSLKFAESDPIVPCNETRWSQKWQSSRPLKRASLSLGSGFWHATGRHSSRRLLRAIPRQVAQTLQADVLWQMGYTGANVRVAVFDTGLSEKHPHFKNVKERTNWTNERTLDDGLGHGTFVAGVIASMRECQGFAPDAELHIFRVFTNNQVSYTSWFLDAFNYAILKKIDVLNLSIGGPDFMDHPFVDKVWELTANNVIMVSAIGNDGPLYGTLNNPADQMDVIGVGGIDFEDNIARFSSRGMTTWELPGGYGRVKPDIVTYGAGVRGSGVKGGCRALSGTSVASPVVAGAVTLLVSTVQKRELVNPASVKQALIASARRLPGVNMFEQGHGKLDLLRAYQILSSYKPQASLSPSYIDLTECPYMWPYCSQPIYYGGMPTIVNVTILNGMGVTGRIVDKPEWRPYLPQNGDNIEVAFSYSSVLWPWSGYLAISISVTKKAASWEGIAQGHIMITVASPAETELKNGAEHTSTVKLPIKVKIIPTPPRSKRVLWDQYHNLRYPPGYFPRDNLRMKNDPLDWNGDHVHTNFRDMYQHLRSMGYFVEVLGAPFTCFDATQYGTLLMVDSEEEYFPEEIAKLRRDVDNGLSLVVFSDWYNTSVMRKVKFYDENTRQWWMPDTGGANVPALNELLSVWNMGFSDGLYEGEFALANHDMYYASGCSIARFPEDGVVITQTFKDQGLEVLKQETAVVDNVPILGLYQIPAEGGGRIVLYGDSNCLDDSHRQKDCFWLLDALLQYTSYGVTPPSLSHSGNRQRPPSGAGLAPPERMEGNHLHRYSKVLEAHLGDPKPRPLPACPHLSWAKPQPLNETAPSNLWKHQKLLSIDLDKVVLPNFRSNRPQVRPLSPGESGAWDIPGGIMPGRYNQEVGQTIPVFAFLGAMVALAFFVVQISKAKSRPKRRRPRAKRPQLAQQAHPARTPSV

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8I5XW81A0A8I5XW81_RATMbtps1964
A0A8L2R475A0A8L2R475_RATMbtps11066

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict301in Ref. 1; AAD27011

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF094821
EMBL· GenBank· DDBJ
AAD27011.1
EMBL· GenBank· DDBJ
mRNA
AABR06099111
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH473972
EMBL· GenBank· DDBJ
EDL92670.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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