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integral membrane protein 2B; transmembrane protein BRI; protein E25B (ITM2B, BRI, BRI2)
Function:
- protease inhibitor
- plays a role in APP processing regulating physiological production of beta amyloid peptide
- restricts docking of gamma-secretase to APP & access of alpha-secretase & beta-secretase to their cleavage APP sequence
- the C-terminal part of the ectodomain is processed by furin & related proteases producing a secreted peptide of 4 to 5 kD
- for the ABRI & ADAN variants, the C-terminal secreted peptide is larger & may produce amyloid fibrils responsible for neuronal dysfunction & dementia
- the remaining part of the ectodomain containing the BRICHOS domain is cleaved by ADAM10 & is secreted as a peptide of 25 kD
- the membrane-bound N-terminal fragment (NTF) of 22 kD is further proteolytically processed by SPPL2A & SPPL2B through regulated intramembrane proteolysis producing a secreted peptide (BRI2C) & an intracellular domain (ICD) released in the cytosol
- interacts with SPPL2A & SPPL2B
- interacts with APP
Structure:
- homodimer; disulfide-linked
- belongs to the ITM2 family
- contains 1 BRICHOS domain
Compartment:
- Golgi membrane, cell membrane
- single-pass type 2 membrane protein
Expression: expressed in brain & in other tissues
Pathology:
- defects in ITM2B are a cause of
a) familial British dementia via generation of ABri amyloid
b) familial Danish dementia via generation of ADan amyloid
General
ITM2 protein
Properties
SIZE: entity length = 266 aa
MW = 30 kD
COMPARTMENT: golgi
MOTIF: transmembrane domain {55-75}
cysteine residue {C89}
MODIFICATION: cysteine residue {C-INTERCHAIN}
BRICHOS {137-231}
MOTIF: cysteine residue {C164}
MODIFICATION: cysteine residue {C223}
N-glycosylation site {N170}
cysteine residue {C223}
MODIFICATION: cysteine residue {C164}
cysteine residue {C248}
MODIFICATION: cysteine residue {C265}
cysteine residue {C265}
MODIFICATION: cysteine residue {C248}
Database Correlations
OMIM correlations
MORBIDMAP 603904
UniProt Q9Y287
Entrez Gene 9445
References
- UniProt :accession Q9Y287
- NIEHS-SNPs
http://egp.gs.washington.edu/data/itm2b/