Human Gene ITM2B (ENST00000378549.5) Description and Page Index
Description: 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. (from UniProt Q9Y287) RefSeq Summary (NM_021999): Amyloid precursor proteins are processed by beta-secretase and gamma-secretase to produce beta-amyloid peptides which form the characteristic plaques of Alzheimer disease. This gene encodes a transmembrane protein which is processed at the C-terminus by furin or furin-like proteases to produce a small secreted peptide which inhibits the deposition of beta-amyloid. Mutations which result in extension of the C-terminal end of the encoded protein, thereby increasing the size of the secreted peptide, are associated with two neurogenerative diseases, familial British dementia and familial Danish dementia. [provided by RefSeq, Oct 2009]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AK130048.1, AK000503.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000647800.2/ ENSP00000497221.1 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END## Gencode Transcript: ENST00000378549.5 Gencode Gene: ENSG00000136156.15 Transcript (Including UTRs) Position: hg38 chr13:48,233,203-48,261,388 Size: 28,186 Total Exon Count: 4 Strand: + Coding Region Position: hg38 chr13:48,233,361-48,261,224 Size: 27,864 Coding Exon Count: 4
ID:ITM2B_HUMAN DESCRIPTION: RecName: Full=Integral membrane protein 2B; AltName: Full=Immature BRI2; Short=imBRI2; AltName: Full=Protein E25B; AltName: Full=Transmembrane protein BRI; Short=Bri; Contains: RecName: Full=BRI2, membrane form; AltName: Full=Mature BRI2; Short=mBRI2; Contains: RecName: Full=BRI2 intracellular domain; Short=BRI2 ICD; Contains: RecName: Full=BRI2C, soluble form; Contains: RecName: Full=Bri23 peptide; Short=Bri2-23; AltName: Full=ABri23; AltName: Full=C-terminal peptide; AltName: Full=P23 peptide; 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. FUNCTION: 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. FUNCTION: Bri23 peptide prevents aggregation of APP beta-amyloid protein 42 peptide into toxic oligomers. 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 beta-amyloid protein 40. 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. SUBCELLULAR LOCATION: 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. SUBCELLULAR LOCATION: Bri23 peptide: Secreted. Note=Detected in the cerebral spinal fluid (CSF). SUBCELLULAR LOCATION: BRI2C, soluble form: Secreted. TISSUE SPECIFICITY: Ubiquitous. Expressed in brain. 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. PTM: Glycosylation at Asn-170 is important for cell surface localization, but doesn't affect furin- and ADAM10-induced proteolytic processing. DISEASE: Defects in ITM2B are a cause of cerebral amyloid angiopathy ITM2B-related type 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=ABri amyloidogenic peptide variant is cleaved at the normal furin processing site to generate peptide that accumulates in the brain and produces amyloid fibrils responsible for neuronal dysfunction and dementia. ABri peptide variant forms fibrila in vitro. DISEASE: Defects in ITM2B are a cause of cerebral amyloid angiopathy ITM2B-related type 2 (CAA-ITM2B2) [MIM:117300]; also known as heredopathia ophthalmo-oto-encephalica. 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=ADan amyloidogenic peptide variant is cleaved at the normal furin processing site to generate peptide that accumulates in the brain and produces amyloid fibrils responsible for neuronal dysfunction and dementia. SIMILARITY: Belongs to the ITM2 family. SIMILARITY: Contains 1 BRICHOS domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/itm2b/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9Y287
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0007399 nervous system development GO:0042985 negative regulation of amyloid precursor protein biosynthetic process GO:0044267 cellular protein metabolic process GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand