Q60HC1 · ITM2B_MACFA
- ProteinIntegral membrane protein 2B
- GeneITM2B
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids266 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
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).
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.
Bri23 peptide prevents aggregation of APP amyloid-beta protein 42 into toxic oligomers.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 243-244 | Cleavage; by furin | ||||
Sequence: RE |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endosome membrane | |
Cellular Component | extracellular exosome | |
Cellular Component | extracellular space | |
Cellular Component | Golgi membrane | |
Cellular Component | Golgi-associated vesicle membrane | |
Cellular Component | organelle membrane | |
Cellular Component | plasma membrane | |
Molecular Function | amyloid-beta binding | |
Biological Process | negative regulation of amyloid precursor protein biosynthetic process |
Names & Taxonomy
Protein names
- Recommended nameIntegral membrane protein 2B
- Alternative names
- Cleaved into 4 chains
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Macaca
Accessions
- Primary accessionQ60HC1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Integral membrane protein 2B
Golgi apparatus membrane ; Single-pass type II membrane protein
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.
BRI2, membrane form
Cell membrane ; Single-pass type II membrane protein
Endosome membrane ; Single-pass type II membrane protein
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.
Bri23 peptide
Note: Detected in the cerebral spinal fluid (CSF).
BRI2C, soluble form
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-54 | Cytoplasmic | ||||
Sequence: MVKVTFNSALAQKEAKKDEPKSGEEALIIPPDAVAVDCKDPDDVVPVGQRRAWC | ||||||
Transmembrane | 55-75 | Helical; Signal-anchor for type II membrane protein | ||||
Sequence: WCMCFGLAFMLAGVILGGAYL | ||||||
Topological domain | 76-266 | Lumenal | ||||
Sequence: YKYFALQPDDVYYCGIKYIKDDVILNEPSADAPAALYQTIEENIKIFEEEEVEFISVPVPEFADSDPANIVHDFNKKLTAYLDLNLDKCYVIPLNTSIVMPPRNLLELLINIKAGTYLPQSYLIHEHMVITDRIENIDHLGFFIYRLCHDKETYKLQRRETIKGIQKREASNCFAIRHFENKFAVETLICS |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, disulfide bond, glycosylation, peptide.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000417469 | ?-243 | BRI2C, soluble form | |||
Sequence: MVKVTFNSALAQKEAKKDEPKSGEEALIIPPDAVAVDCKDPDDVVPVGQRRAWCWCMCFGLAFMLAGVILGGAYLYKYFALQPDDVYYCGIKYIKDDVILNEPSADAPAALYQTIEENIKIFEEEEVEFISVPVPEFADSDPANIVHDFNKKLTAYLDLNLDKCYVIPLNTSIVMPPRNLLELLINIKAGTYLPQSYLIHEHMVITDRIENIDHLGFFIYRLCHDKETYKLQRRETIKGIQKR | ||||||
Chain | PRO_0000417468 | 1-? | BRI2 intracellular domain | |||
Chain | PRO_0000417467 | 1-243 | BRI2, membrane form | |||
Sequence: MVKVTFNSALAQKEAKKDEPKSGEEALIIPPDAVAVDCKDPDDVVPVGQRRAWCWCMCFGLAFMLAGVILGGAYLYKYFALQPDDVYYCGIKYIKDDVILNEPSADAPAALYQTIEENIKIFEEEEVEFISVPVPEFADSDPANIVHDFNKKLTAYLDLNLDKCYVIPLNTSIVMPPRNLLELLINIKAGTYLPQSYLIHEHMVITDRIENIDHLGFFIYRLCHDKETYKLQRRETIKGIQKR | ||||||
Chain | PRO_0000154821 | 1-266 | Integral membrane protein 2B | |||
Sequence: MVKVTFNSALAQKEAKKDEPKSGEEALIIPPDAVAVDCKDPDDVVPVGQRRAWCWCMCFGLAFMLAGVILGGAYLYKYFALQPDDVYYCGIKYIKDDVILNEPSADAPAALYQTIEENIKIFEEEEVEFISVPVPEFADSDPANIVHDFNKKLTAYLDLNLDKCYVIPLNTSIVMPPRNLLELLINIKAGTYLPQSYLIHEHMVITDRIENIDHLGFFIYRLCHDKETYKLQRRETIKGIQKREASNCFAIRHFENKFAVETLICS | ||||||
Disulfide bond | 89 | Interchain | ||||
Sequence: C | ||||||
Disulfide bond | 164↔223 | |||||
Sequence: CYVIPLNTSIVMPPRNLLELLINIKAGTYLPQSYLIHEHMVITDRIENIDHLGFFIYRLC | ||||||
Glycosylation | 170 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Peptide | PRO_0000417470 | 244-266 | Bri23 peptide | |||
Sequence: EASNCFAIRHFENKFAVETLICS | ||||||
Disulfide bond | 248↔265 | |||||
Sequence: CFAIRHFENKFAVETLIC |
Post-translational modification
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).
Glycosylation at Asn-170 is important for cell surface localization, but doesn't affect furin- and ADAM10-induced proteolytic processing.
Keywords
- PTM
PTM databases
Interaction
Subunit
Homodimer; disulfide-linked. Interacts with SPPL2A and SPPL2B. Interacts with APP. Mature BRI2 (mBRI2) interacts with the APP amyloid-beta A4 protein; the interaction occurs at the cell surface and in the endocytic compartments and enable alpha- and beta-secretase-induced APP cleavage inhibition. Mature BRI2 (mBRI2) interacts with the APP C99; the interaction occurs in the endocytic compartments and enable gamma-secretase-induced C99 cleavage inhibition. May form heterodimers with Bri23 peptide and APP amyloid-beta protein 40 (By similarity).
Interacts with ADAM7 in sperm; the interaction increases following capacitation (By similarity).
Interacts with ADAM7 in sperm; the interaction increases following capacitation (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 102-134 | Necessary for interaction with APP and inhibitor effects on APP processing | ||||
Sequence: EPSADAPAALYQTIEENIKIFEEEEVEFISVPV | ||||||
Domain | 137-231 | BRICHOS | ||||
Sequence: FADSDPANIVHDFNKKLTAYLDLNLDKCYVIPLNTSIVMPPRNLLELLINIKAGTYLPQSYLIHEHMVITDRIENIDHLGFFIYRLCHDKETYKL |
Sequence similarities
Belongs to the ITM2 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length266
- Mass (Da)30,338
- Last updated2004-11-23 v1
- Checksum3A7D8CA259F1F627
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 230 | in Ref. 1; BAC20585 | ||||
Sequence: K → I |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB083306 EMBL· GenBank· DDBJ | BAC20585.1 EMBL· GenBank· DDBJ | mRNA | ||
AB125206 EMBL· GenBank· DDBJ | BAD51994.1 EMBL· GenBank· DDBJ | mRNA | ||
AB168350 EMBL· GenBank· DDBJ | BAE00473.1 EMBL· GenBank· DDBJ | mRNA |