Q60HC1 · ITM2B_MACFA

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.

126620406080100120140160180200220240260
TypeIDPosition(s)Description
Site243-244Cleavage; by furin

GO annotations

AspectTerm
Cellular Componentendosome membrane
Cellular Componentextracellular exosome
Cellular Componentextracellular space
Cellular ComponentGolgi membrane
Cellular ComponentGolgi-associated vesicle membrane
Cellular Componentorganelle membrane
Cellular Componentplasma membrane
Molecular Functionamyloid-beta binding
Biological Processnegative regulation of amyloid precursor protein biosynthetic process

Names & Taxonomy

Protein names

Gene names

    • Name
      ITM2B
    • Synonyms
      BRI
    • ORF names
      QflA-11829, QflA-12336, QtsA-11432

Organism names

Accessions

  • Primary accession
    Q60HC1
  • Secondary accessions
    • Q4R8U8
    • Q8HXY3

Proteomes

Organism-specific databases

Subcellular Location

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

Secreted
Note: Detected in the cerebral spinal fluid (CSF).

BRI2C, soluble form

Secreted

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-54Cytoplasmic
Transmembrane55-75Helical; Signal-anchor for type II membrane protein
Topological domain76-266Lumenal

Keywords

PTM/Processing

Features

Showing features for chain, disulfide bond, glycosylation, peptide.

TypeIDPosition(s)Description
ChainPRO_0000417469?-243BRI2C, soluble form
ChainPRO_00004174681-?BRI2 intracellular domain
ChainPRO_00004174671-243BRI2, membrane form
ChainPRO_00001548211-266Integral membrane protein 2B
Disulfide bond89Interchain
Disulfide bond164↔223
Glycosylation170N-linked (GlcNAc...) asparagine
PeptidePRO_0000417470244-266Bri23 peptide
Disulfide bond248↔265

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 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).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, domain.

TypeIDPosition(s)Description
Region102-134Necessary for interaction with APP and inhibitor effects on APP processing
Domain137-231BRICHOS

Sequence similarities

Belongs to the ITM2 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    266
  • Mass (Da)
    30,338
  • Last updated
    2004-11-23 v1
  • Checksum
    3A7D8CA259F1F627
MVKVTFNSALAQKEAKKDEPKSGEEALIIPPDAVAVDCKDPDDVVPVGQRRAWCWCMCFGLAFMLAGVILGGAYLYKYFALQPDDVYYCGIKYIKDDVILNEPSADAPAALYQTIEENIKIFEEEEVEFISVPVPEFADSDPANIVHDFNKKLTAYLDLNLDKCYVIPLNTSIVMPPRNLLELLINIKAGTYLPQSYLIHEHMVITDRIENIDHLGFFIYRLCHDKETYKLQRRETIKGIQKREASNCFAIRHFENKFAVETLICS

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict230in Ref. 1; BAC20585

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

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