| IED ID | IndEnz0002004935 |
| Enzyme Type ID | protease004935 |
| Protein Name |
Integral membrane protein 2B Immature BRI2 imBRI2 Protein E25B Transmembrane protein BRI Bri Cleaved into: BRI2, membrane form Mature BRI2 mBRI2 ; BRI2 intracellular domain BRI2 ICD ; BRI2C, soluble form; Bri23 peptide Bri2-23 ABri23 C-terminal peptide P23 peptide |
| Gene Name | Itm2b |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MVKVTFNSALAQKEAKKDEPKSSEEALIVPPDAVAVDCKDPGDVVPVGQRRAWCWCMCFGLAFMLAGVILGGAYLYKYFALQPDDVYYCGLKYIKDDVILNEPSADAPAARYQTIEENIKIFEEDAVEFISVPVPEFADSDPANIVHDFNKKLTAYLDLNLDKCYVIPLNTSIVMPPKNLLELLINIKAGTYLPQSYLIHEHMVITDRIENVDNLGFFIYRLCHDKETYKLQRRETIRGIQKREASNCFTIRHFENKFAVETLICS |
| Enzyme Length | 266 |
| Uniprot Accession Number | O89051 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Plays a regulatory role in the processing of the amyloid-beta A4 precursor protein (APP) and acts as an inhibitor of the amyloid-beta peptide aggregation and fibrils deposition. Plays a role in the induction of neurite outgrowth. Functions as a protease inhibitor by blocking access of secretases to APP cleavage sites (By similarity). {ECO:0000250}.; FUNCTION: Mature BRI2 (mBRI2) functions as a modulator of the amyloid-beta A4 precursor protein (APP) processing leading to a strong reduction in the secretion of secretase-processed amyloid-beta protein 40 and amyloid-beta protein 42. {ECO:0000250}.; FUNCTION: Bri23 peptide prevents aggregation of APP amyloid-beta protein 42 into toxic oligomers. {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (4); Disulfide bond (3); Domain (1); Glycosylation (1); Peptide (1); Region (1); Site (1); Topological domain (2); Transmembrane (1) |
| Keywords | Cell membrane;Disulfide bond;Endosome;Glycoprotein;Golgi apparatus;Membrane;Reference proteome;Secreted;Signal-anchor;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Integral membrane protein 2B]: Golgi apparatus membrane {ECO:0000250|UniProtKB:Q9Y287}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9Y287}. Note=Immature BRI2 (imBRI2) is cleaved by furin in the Golgi into mBRI2 and a Bri23 peptide. mBRI2 is transported to the plasma membrane and Bri23 peptide is secreted. {ECO:0000250|UniProtKB:Q9Y287}.; SUBCELLULAR LOCATION: [BRI2, membrane form]: Cell membrane {ECO:0000250|UniProtKB:Q9Y287}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9Y287}. Endosome membrane {ECO:0000250|UniProtKB:Q9Y287}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9Y287}. Note=Mature BRI2 (mBRI2) needs to be transported from the endoplasmic reticulum compartment to the cell membrane in order to be able to inhibit APP processing. {ECO:0000250|UniProtKB:Q9Y287}.; SUBCELLULAR LOCATION: [Bri23 peptide]: Secreted {ECO:0000250|UniProtKB:Q9Y287}. Note=Detected in the cerebral spinal fluid (CSF). {ECO:0000250|UniProtKB:Q9Y287}.; SUBCELLULAR LOCATION: [BRI2C, soluble form]: Secreted {ECO:0000250|UniProtKB:Q9Y287}. |
| Modified Residue | |
| Post Translational Modification | PTM: The ectodomain C-terminal part of the imBRI2 is processed by furin producing a secreted Bri23 peptide and a mature BRI2, membrane form (mBRI2). The remaining part of the ectodomain of mBRI2 containing the BRICHOS domain is cleaved by ADAM10 and is secreted (BRI2C, soluble form). The membrane-bound N-terminal fragment (BRI2C, membrane form) is further proteolytically processed by SPPL2A and SPPL2B through regulated intramembrane proteolysis producing a secreted C-peptide and a BRI2 intracellular domain (BRI2 ICD) released in the cytosol. Shedding by ADAM10 facilitates intramembrane cleavage but is not absolutely required for BRI2 ICD generation (By similarity). {ECO:0000250}.; PTM: Glycosylation at Asn-170 is important for cell surface localization, but doesn't affect furin- and ADAM10-induced proteolytic processing. {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11044609; 11217851; 12082633; 12442332; 12466851; 14610273; 14741382; 16107646; 16267818; 16602821; 16612985; 16919471; 17145500; 17873332; 18440095; 18554416; 18753367; 19748705; 19924302; 20945367; 21048150; 21098268; 21267068; 21587206; 21677750; 21873424; 22514310; 23418567; 23451158; 24026677; 25588837; 26246218; 26868295; 30890756; 8000140; |
| Motif | |
| Gene Encoded By | |
| Mass | 30,260 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |