InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ITM2B

Summary

InnateDB Protein

IDBP-31935.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ITM2B

Protein Name

integral membrane protein 2B

Synonyms

ABRI; BRI; BRI2; BRICD2B; E25B; E3-16; FBD; imBRI2;

Species

Homo sapiens

Ensembl Protein

ENSP00000367828

InnateDB Gene

IDBG-31933 (ITM2B)

Protein Structure

UniProt Annotation

Function

Plays a regulatory role in the processing of the beta- amyloid A4 precursor protein (APP) and acts as an inhibitor of the beta-amyloid 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.Mature BRI2 (mBRI2) functions as a modulator of the beta-amyloid A4 precursor protein (APP) processing leading to a strong reduction in the secretion of secretase-processed beta- amyloid protein 40 and beta-amyloid protein 42.Bri23 peptide prevents aggregation of APP beta-amyloid protein 42 peptide into toxic oligomers.

Subcellular Localization

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.

Disease Associations

Cerebral amyloid angiopathy, ITM2B-related 1 (CAA-ITM2B1) [MIM:176500]: A disorder characterized by amyloid deposition in the walls of cerebral blood vessels and neurodegeneration in the central nervous system. Cerebral amyloid angiopathy, non-neuritic and perivascular plaques and neurofibrillary tangles are the predominant pathological lesions. Clinical features include progressive mental deterioration, spasticity and muscular rigidity. Note=The disease is caused by mutations affecting the gene represented in this entry. A single base substitution at the stop codon of ITM2B generates a 277-residue precursor that is cleaved at the normal furin processing site to generate the ABri amyloidogenic peptide (PubMed:10391242). ABri accumulates in the brain and produces amyloid fibrils responsible for neuronal dysfunction and dementia. ABri peptide variant forms fibrils in vitro (PubMed:10526337). {ECO:0000269PubMed:10391242, ECO:0000269PubMed:10526337}.Cerebral amyloid angiopathy, ITM2B-related 2 (CAA-ITM2B2) [MIM:117300]: A disorder characterized by amyloid deposition in the walls of the blood vessels of the cerebrum, choroid plexus, cerebellum, spinal cord and retina. Plaques and neurofibrillary tangles are observed in the hippocampus. Clinical features include progressive ataxia, dementia, cataracts and deafness. Note=The disease is caused by mutations affecting the gene represented in this entry. A decamer duplication in the 3' region of ITM2B results in the production of the ADan amyloidogenic peptide (PubMed:10781099). ADan is generated by cleavage of the mutated precursor at the normal furin processing site. ADan accumulates in the brain and produces amyloid fibrils responsible for neuronal dysfunction and dementia. {ECO:0000269PubMed:10781099}.

Tissue Specificity

Ubiquitous. Expressed in brain.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 5 experimentally validated interaction(s) in this database.

Experimentally validated
Total	5 [view]
Protein-Protein	4 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001540	beta-amyloid binding
GO:0005515	protein binding
GO:0005524	ATP binding

Biological Process

GO:0007399	nervous system development
GO:0042985	negative regulation of amyloid precursor protein biosynthetic process
GO:0097192	extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component

GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0010008	endosome membrane
GO:0016020	membrane
GO:0030660	Golgi-associated vesicle membrane
GO:0031301	integral component of organelle membrane
GO:0043231	intracellular membrane-bounded organelle
GO:0070062	extracellular vesicular exosome