Q8CHX6 · MBTP2_MOUSE

  • Protein
    Membrane-bound transcription factor site-2 protease
  • Gene
    Mbtps2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at transcript level
  • Annotation score
    5/5

Function

function

Zinc metalloprotease that mediates intramembrane proteolysis of proteins such as ATF6, ATF6B, SREBF1/SREBP1 and SREBF2/SREBP2. Catalyzes the second step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2: cleaves SREBPs within the first transmembrane segment, thereby releasing the N-terminal segment with a portion of the transmembrane segment attached. Mature N-terminal SREBP fragments shuttle to the nucleus and activate gene transcription. Also mediates the second step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B). Involved in intramembrane proteolysis during bone formation. In astrocytes and osteoblasts, upon DNA damage and ER stress, mediates the second step of the regulated intramembrane proteolytic activation of the transcription factor CREB3L1, leading to the inhibition of cell-cycle progression.

Catalytic activity

  • Cleaves several transcription factors that are type-2 transmembrane proteins within membrane-spanning domains. Known substrates include sterol regulatory element-binding protein (SREBP) -1, SREBP-2 and forms of the transcriptional activator ATF6. SREBP-2 is cleaved at the site 477-DRSRILL-|-CVLTFLCLSFNPLTSLLQWGGA-505. The residues Asn-Pro, 11 residues distal to the site of cleavage in the membrane-spanning domain, are important for cleavage by S2P endopeptidase. Replacement of either of these residues does not prevent cleavage, but there is no cleavage if both of these residues are replaced.
    EC:3.4.24.85 (UniProtKB | ENZYME | Rhea)

Cofactor

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )

Note: Binds 1 zinc ion per subunit.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site167Zn2+ (UniProtKB | ChEBI); catalytic
Active site168
Binding site171Zn2+ (UniProtKB | ChEBI); catalytic

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentendoplasmic reticulum membrane
Cellular ComponentGolgi membrane
Molecular Functionmetal ion binding
Molecular Functionmetalloendopeptidase activity
Molecular Functiontranscription regulator activator activity
Biological Processbone maturation
Biological Processcholesterol metabolic process
Biological Processmembrane protein intracellular domain proteolysis
Biological Processmitotic G2 DNA damage checkpoint signaling
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processprotein maturation
Biological Processregulation of response to endoplasmic reticulum stress
Biological Processresponse to endoplasmic reticulum stress

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Membrane-bound transcription factor site-2 protease
  • EC number
  • Alternative names
    • Endopeptidase S2P

Gene names

    • Name
      Mbtps2

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q8CHX6
  • Secondary accessions
    • A2AC85

Proteomes

Organism-specific databases

Subcellular Location

Membrane
; Multi-pass membrane protein
Cytoplasm
Golgi apparatus membrane
; Multi-pass membrane protein

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-3Cytoplasmic
Transmembrane4-24Helical
Topological domain25-74Lumenal
Transmembrane75-95Helical
Transmembrane96-107Helical
Topological domain108-140Lumenal
Transmembrane141-165Helical
Transmembrane170-182Helical
Transmembrane183-205Helical
Transmembrane225-247Helical
Topological domain248-442Lumenal
Transmembrane443-460Helical
Transmembrane461-472Helical
Topological domain473-488Lumenal
Transmembrane489-509Helical
Topological domain510-515Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for chain, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00002615921-515Membrane-bound transcription factor site-2 protease
Glycosylation333N-linked (GlcNAc...) asparagine

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Protein-protein interaction databases

Miscellaneous

Family & Domains

Sequence similarities

Belongs to the peptidase M50A family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    515
  • Mass (Da)
    56,960
  • Last updated
    2003-03-01 v1
  • Checksum
    E7C3A93A58D17A21
MIPVSLLVVVVGGWTAVYLADLVLKSSVYFKHSYEDWLENNGLSISPFHIRWQTSIFNRAFYSWGRRKARMLYQWFNFGMVFGVIAMFSSFFLLGKTLMQTLAQMMADSPSPYSSSSSSSSSSSSSSSSSSSLHNEQVLQVVVPGINLPVNQLTYFFAAVLISGVVHEIGHGIAAIREQVRFNGFGIFLFIIYPGAFVDLFTTHLQLISPVQQLRIFCAGIWHNFVLALLGILALVLLPVILLPFYYTGVGVLITEVAEDSPAIGPRGLFVGDLVTHLQDCPVTNVQDWNECLDTIAYEPQIGYCISASTLQQLSFPVRAYKRLDGSTECCNNHSLTDVCFSYRNNFNKRLHTCLPARKAVEATQVCRSNKDCKSGASSSFCIVPSLETHTRLIKVKHPPQIDMLYVGHPLHLHYTVSITSFIPRFNFLSIDLPVIVETFVKYLISLSGALAIVNAVPCFALDGQWILNSFLDATLTSVIGDNDVKDLIGFFILLGGSVLLAANVTLGLWMVTAR

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AK148325
EMBL· GenBank· DDBJ
BAE28482.1
EMBL· GenBank· DDBJ
mRNA
AK164486
EMBL· GenBank· DDBJ
BAE37807.1
EMBL· GenBank· DDBJ
mRNA
AL663072
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC038343
EMBL· GenBank· DDBJ
AAH38343.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

Any 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. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp