O54862 · MBTP2_CRIGR

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 site162Zn2+ (UniProtKB | ChEBI); catalytic
Active site163
Binding site166Zn2+ (UniProtKB | ChEBI); catalytic

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular ComponentGolgi membrane
Molecular Functionmetal ion binding
Molecular Functionmetalloendopeptidase activity
Molecular FunctionRNA polymerase II-specific DNA-binding transcription factor binding
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 DNA-binding transcription factor activity
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
    • Sterol regulatory element-binding proteins intramembrane protease (SREBPs intramembrane protease)

Gene names

    • Name
      MBTPS2
    • Synonyms
      S2P

Organism names

Accessions

  • Primary accession
    O54862

Proteomes

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 domain108-135Lumenal
Transmembrane136-160Helical
Transmembrane165-177Helical
Transmembrane178-200Helical
Transmembrane220-242Helical
Topological domain243-437Lumenal
Transmembrane438-455Helical
Transmembrane456-467Helical
Topological domain468-483Lumenal
Transmembrane484-504Helical
Topological domain505-510Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for chain, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00000884811-510Membrane-bound transcription factor site-2 protease
Glycosylation328N-linked (GlcNAc...) asparagine

Keywords

Proteomic databases

PTM databases

Family & Domains

Sequence similarities

Belongs to the peptidase M50A family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    510
  • Mass (Da)
    56,499
  • Last updated
    1998-06-01 v1
  • Checksum
    12B6B2257C0DA7A4
MIPVSLVVVVVGGWTAVYLADLVLKSSVYFKHSYEDWLEKNGLSISPFHIRWQTSVFNRAFYSWGRRKARMLYQWFNFGMVFGVIAMFSSFFLLGKTLMQTLAQMMADSPSSSSSSSSSSSSSSSSSIHNEQVLQVVVPGINLPVNQLTYFFAAVLISGVVHEIGHGIAAIREQVRFNGFGIFLFIIYPGAFVDLFTTHLQLISPVQQLRIFCAGIWHNFVLALLGILALVLLPVILLPFYYTGVGVLITEVAEDSPAIGPRGLFVGDLVTHLQDCPVTNVQDWNECLDTIAYEPQIGYCISASTLQQLSFPVRAYKRLDGSTECCNNHSLTDVCFSYRNNFNKRLHTCLPARKAVEATQVCRTNKDCKTSSSSSFCIVPSLETHTRLIKVKHPPQIDMLYVGHPLHLHYTVSITSFIPRFNFLSIDLPVIVETFVKYLISLSGALAIVNAVPCFALDGQWILNSFLDATLTSVIGDNDVKDLIGFFILLGGSVLLAANVTLGLWMVTAR

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF019611
EMBL· GenBank· DDBJ
AAC53526.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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