O54862 · MBTP2_CRIGR
- ProteinMembrane-bound transcription factor site-2 protease
- GeneMBTPS2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids510 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
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.
Cofactor
Note: Binds 1 zinc ion per subunit.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | Golgi membrane | |
Molecular Function | metal ion binding | |
Molecular Function | metalloendopeptidase activity | |
Molecular Function | RNA polymerase II-specific DNA-binding transcription factor binding | |
Molecular Function | transcription regulator activator activity | |
Biological Process | bone maturation | |
Biological Process | cholesterol metabolic process | |
Biological Process | membrane protein intracellular domain proteolysis | |
Biological Process | mitotic G2 DNA damage checkpoint signaling | |
Biological Process | positive regulation of DNA-binding transcription factor activity | |
Biological Process | positive regulation of transcription by RNA polymerase II | |
Biological Process | protein maturation | |
Biological Process | regulation of response to endoplasmic reticulum stress | |
Biological Process | response to endoplasmic reticulum stress |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameMembrane-bound transcription factor site-2 protease
- EC number
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Cricetidae > Cricetinae > Cricetulus
Accessions
- Primary accessionO54862
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Multi-pass membrane protein
Golgi apparatus membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-3 | Cytoplasmic | ||||
Sequence: MIP | ||||||
Transmembrane | 4-24 | Helical | ||||
Sequence: VSLVVVVVGGWTAVYLADLVL | ||||||
Topological domain | 25-74 | Lumenal | ||||
Sequence: KSSVYFKHSYEDWLEKNGLSISPFHIRWQTSVFNRAFYSWGRRKARMLYQ | ||||||
Transmembrane | 75-95 | Helical | ||||
Sequence: WFNFGMVFGVIAMFSSFFLLG | ||||||
Transmembrane | 96-107 | Helical | ||||
Sequence: KTLMQTLAQMMA | ||||||
Topological domain | 108-135 | Lumenal | ||||
Sequence: DSPSSSSSSSSSSSSSSSSSIHNEQVLQ | ||||||
Transmembrane | 136-160 | Helical | ||||
Sequence: VVVPGINLPVNQLTYFFAAVLISGV | ||||||
Transmembrane | 165-177 | Helical | ||||
Sequence: GHGIAAIREQVRF | ||||||
Transmembrane | 178-200 | Helical | ||||
Sequence: NGFGIFLFIIYPGAFVDLFTTHL | ||||||
Transmembrane | 220-242 | Helical | ||||
Sequence: FVLALLGILALVLLPVILLPFYY | ||||||
Topological domain | 243-437 | Lumenal | ||||
Sequence: TGVGVLITEVAEDSPAIGPRGLFVGDLVTHLQDCPVTNVQDWNECLDTIAYEPQIGYCISASTLQQLSFPVRAYKRLDGSTECCNNHSLTDVCFSYRNNFNKRLHTCLPARKAVEATQVCRTNKDCKTSSSSSFCIVPSLETHTRLIKVKHPPQIDMLYVGHPLHLHYTVSITSFIPRFNFLSIDLPVIVETFVK | ||||||
Transmembrane | 438-455 | Helical | ||||
Sequence: YLISLSGALAIVNAVPCF | ||||||
Transmembrane | 456-467 | Helical | ||||
Sequence: ALDGQWILNSFL | ||||||
Topological domain | 468-483 | Lumenal | ||||
Sequence: DATLTSVIGDNDVKDL | ||||||
Transmembrane | 484-504 | Helical | ||||
Sequence: IGFFILLGGSVLLAANVTLGL | ||||||
Topological domain | 505-510 | Cytoplasmic | ||||
Sequence: WMVTAR |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000088481 | 1-510 | Membrane-bound transcription factor site-2 protease | |||
Sequence: MIPVSLVVVVVGGWTAVYLADLVLKSSVYFKHSYEDWLEKNGLSISPFHIRWQTSVFNRAFYSWGRRKARMLYQWFNFGMVFGVIAMFSSFFLLGKTLMQTLAQMMADSPSSSSSSSSSSSSSSSSSIHNEQVLQVVVPGINLPVNQLTYFFAAVLISGVVHEIGHGIAAIREQVRFNGFGIFLFIIYPGAFVDLFTTHLQLISPVQQLRIFCAGIWHNFVLALLGILALVLLPVILLPFYYTGVGVLITEVAEDSPAIGPRGLFVGDLVTHLQDCPVTNVQDWNECLDTIAYEPQIGYCISASTLQQLSFPVRAYKRLDGSTECCNNHSLTDVCFSYRNNFNKRLHTCLPARKAVEATQVCRTNKDCKTSSSSSFCIVPSLETHTRLIKVKHPPQIDMLYVGHPLHLHYTVSITSFIPRFNFLSIDLPVIVETFVKYLISLSGALAIVNAVPCFALDGQWILNSFLDATLTSVIGDNDVKDLIGFFILLGGSVLLAANVTLGLWMVTAR | ||||||
Glycosylation | 328 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Sequence
- Sequence statusComplete
- Length510
- Mass (Da)56,499
- Last updated1998-06-01 v1
- Checksum12B6B2257C0DA7A4
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF019611 EMBL· GenBank· DDBJ | AAC53526.1 EMBL· GenBank· DDBJ | mRNA |