Property Summary

NCBI Gene PubMed Count 55
PubMed Score 330.54
PubTator Score 111.49

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (6)

Disease log2 FC p
psoriasis 1.300 1.1e-04
medulloblastoma, large-cell -1.400 1.2e-03
lung cancer -1.200 5.8e-04
lung adenocarcinoma -1.200 2.1e-06
Breast cancer -1.200 1.3e-05
ovarian cancer -2.400 4.7e-10

Gene RIF (36)

PMID Text
26528887 Data depict roles for Bri2 and apolipoprotein E4 (ApoE4) proteins in a long-term memory regulation pathway. A single mutation in one Itm2b/Bri2 allele can affect both long-term and working memory, while ApoE4 seems to regulate short-term/working memory.
26515131 when BRI2 is phosphorylated a significant increase in neuronal outgrowth and differentiation is evident
26459115 familial Danish dementia mutation and pE posttranslational modification are primary elements driving intact ADan into an amyloidogenic/neurotoxic pathway while truncations at the C-terminus eliminate the pro-amyloidogenic characteristics of the molecule
25957407 Cystine-linked oligomers of ABri are toxic to neurons and block long-term potentiation.
25557390 Data indicate integral membrane 2B (ITM2B) as a target of B-cell CLL/lymphoma 6 protein (BCL6) repression in lymphoma.
25261792 Data indicate that the mutation originates the highly amyloidogenic molecule integral membrane protein 2B ABri.
24524963 It binds amyloid precursor protein to halt amyloid-b production and inhibits amyloid-b aggregation via its BRICHOS-domain suggesting a link between BRI2 and Alzheimer's disease (AD)
24473189 This review support the hypothesis that BRI2 change during disease devel-opment, and thus may have a role in Alzheimer disease.
24099305 Structural modeling of transmembrane (BRICHOS) domains of BRI2/ITM2B and SFTPC (pulmonary surfactant protein C) precursor identifies conserved region structurally complementary to beta-sheet/amyloid-prone region in BRICHOS domain-containing proteins.
24026677 Findings highlight pathogenic mechanism(s) associated with ITM2B mutations underlying dementia or retinal disease and add a new candidate to the list of genes involved in inherited retinal dystrophies.
23701002 These results suggest that BRI2 may prevent access of BACE1 to APP and the BRI2/BACE1 interaction may mediate the reduction in BACE1 levels.
23418567 Data indicate that double transgenic (Tg-FDD-Tau) mice showed a significant decrease in synaptophysin levels.
23261769 Similarities of ABri and ADan to Abeta in Alzheimer's disease suggest that posttranslational pGlu-modification of amyloid peptides might represent general pathological mechanism leading to increased aggregation and toxicity forms of degenerative dementias.
22194595 The alpha-helical content of the transmembrane domain of the British dementia protein-2 (Bri2) determines its processing by signal peptide peptidase-like 2b (SPPL2b).
22190034 HIV-1 gp160 is identified to have a physical interaction with integral membrane protein 2B (ITM2B) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses
21873424 BRI2 protein regulates beta-amyloid degradation by increasing levels of secreted insulin-degrading enzyme (IDE).
21841249 Neurological effects of the Danish form of BRI2 dementia caused by toxic amyloid Abeta protein precursor metabolites suggest that familial Danish and Alzheimer's dementias share common pathogenic mechanisms.
21752865 BRI2 is N-glycosylated at Asn170 and show that this post-translational modification is essential for its expression at the cell surface but not for its proteolytic processing.
21587206 Knock-in mice with familial Danish dementia, a mouse model congruous to human disease since they carry one mutant and one wild-type Bri2 allele, show that the Danish mutation causes loss of Bri2 protein, synaptic plasticity and memory impairment.
21048150 The British mutation drastically reduces expression of mature BRI2 in both knock-in mice and the brains of familial British dementia patients.
20600910 Decreased cerebrospinal fluid levels of Bri2-23, a peptide cleaved from Bri2, significantly associates with multiple scleerosis patients with cerebellar dysfunction and cognition impairment.
20036644 These data suggest a model for how the processing of Bri2 and APP are interrelated.
19748705 BRI2 is a specific inhibitor that reduces access of secretase to amyloid-betaprecursor protein (APP) in intracellular compartments where APP is normally processed.
19366692 BRI3 inhibits the various processing of amyloid protein precursor by blocking the access of alpha- and beta-secretases in a manner unlike BRI2.
18524908 Expression of wild-type human ITM2B reduces cerebral amyloid beta deposition in a mouse model of Alzheimer's disease.
18440095 BRI2 dimerizes in cells and that dimers are held via non-covalent interactions and via disulfide bridges between the cysteines at position 89. Additionally, we showed that BRI2 dimers are formed in the ER and appear at the cell surface.
18282158 in familial British dementia the mutated precursor BRi2 protein may undergo furin cleavage within neurones to produce the amyloid peptide ABri
17965014 SPPL2a and SPPL2b mediate the intramembrane cleavage, whereas neither SPP nor SPPL3 is capable of processing the Bri2 N-terminal fragment.
16612984 early-onset dementia is linked to specific mutations in the BRI2 {REVIEW}
16027166 BRI2 had a modulatory effect on amyloid precursor protein (APP) processing, increasing levels of cellular APP and COOH-terminal fragments while decreasing COOH-terminal fragments and secretion of total APP and Abeta peptides.
15983050 BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production
15968464 Mutations at or near the stop codon of the chromosome 13 gene BRI2 that cause generation of longer-than-normal protein products.
14656991 expression of wild-type British or Danish mutants of BRI2, in mouse neuroblastoma N2a cells that do not express endogenous BRI2, induces elongation of neurites, which suggests a role for this protein in differentiation of neuronal cells
14586629 While a physiological role of BRI in brain remains to be determined, the behavior of BRI in diverse brain lesions appears to be somewhat analogous to that of amyloid precursor protein.
12903036 Data show that the expression of BRI gene was up-regulated in the highly metastatic cell line and down-regulated in the low metastatic cell line and there was no relation between BRI gene differential expression and rearrangements of chromosome.
12196136 oxidized form of ABri and reduced form of ADan are toxic to human neuronal cell lines in culture

AA Sequence

MVKVTFNSALAQKEAKKDEPKSGEEALIIPPDAVAVDCKDPDDVVPVGQRRAWCWCMCFGLAFMLAGVIL      1 - 70
GGAYLYKYFALQPDDVYYCGIKYIKDDVILNEPSADAPAALYQTIEENIKIFEEEEVEFISVPVPEFADS     71 - 140
DPANIVHDFNKKLTAYLDLNLDKCYVIPLNTSIVMPPRNLLELLINIKAGTYLPQSYLIHEHMVITDRIE    141 - 210
NIDHLGFFIYRLCHDKETYKLQRRETIKGIQKREASNCFAIRHFENKFAVETLICS                  211 - 266
//

Text Mined References (58)

PMID Year Title
26528887 2015 Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory.
26515131 2016 BRI2 and BRI3 are functionally distinct phosphoproteins.
26459115 2016 Oxidative stress and mitochondria-mediated cell death mechanisms triggered by the familial Danish dementia ADan amyloid.
25957407 2015 The Familial British Dementia Mutation Promotes Formation of Neurotoxic Cystine Cross-linked Amyloid Bri (ABri) Oligomers.
25557390 2015 The ITM2B (BRI2) gene is a target of BCL6 repression: Implications for lymphomas and neurodegenerative diseases.
25416956 2014 A proteome-scale map of the human interactome network.
25261792 2014 Mitochondrial dysfunction induced by a post-translationally modified amyloid linked to a familial mutation in an alternative model of neurodegeneration.
24524963 2014 BRI2-BRICHOS is increased in human amyloid plaques in early stages of Alzheimer's disease.
24473189 2014 Role of BRI2 in dementia.
24099305 2013 The BRICHOS domain, amyloid fibril formation, and their relationship.
24026677 2014 The familial dementia gene revisited: a missense mutation revealed by whole-exome sequencing identifies ITM2B as a candidate gene underlying a novel autosomal dominant retinal dystrophy in a large family.
23701002 2013 BRI2 interacts with BACE1 and regulates its cellular levels by promoting its degradation and reducing its mRNA levels.
23533145 2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
23418567 2013 Increased tau phosphorylation and tau truncation, and decreased synaptophysin levels in mutant BRI2/tau transgenic mice.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23261769 2013 Abundant pyroglutamate-modified ABri and ADan peptides in extracellular and vascular amyloid deposits in familial British and Danish dementias.
22194595 2012 The ?-helical content of the transmembrane domain of the British dementia protein-2 (Bri2) determines its processing by signal peptide peptidase-like 2b (SPPL2b).
22170863 2012 ?- but not ?-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia.
21873424 2011 BRI2 protein regulates ?-amyloid degradation by increasing levels of secreted insulin-degrading enzyme (IDE).
21841249 2011 Increased A?PP processing in familial Danish dementia patients.
21752865 2011 Glycosylation of BRI2 on asparagine 170 is involved in its trafficking to the cell surface but not in its processing by furin or ADAM10.
21587206 2011 APP heterozygosity averts memory deficit in knockin mice expressing the Danish dementia BRI2 mutant.
21048150 2010 Memory deficits due to familial British dementia BRI2 mutation are caused by loss of BRI2 function rather than amyloidosis.
20600910 2010 Bri2-23 is a potential cerebrospinal fluid biomarker in multiple sclerosis.
20036644 2010 The extracellular domain of Bri2 (ITM2B) binds the ABri peptide (1-23) and amyloid beta-peptide (Abeta1-40): Implications for Bri2 effects on processing of amyloid precursor protein and Abeta aggregation.
19946888 2010 Defining the membrane proteome of NK cells.
19849849 2009 CD74 interacts with APP and suppresses the production of Abeta.
19748705 2011 Maturation of BRI2 generates a specific inhibitor that reduces APP processing at the plasma membrane and in endocytic vesicles.
19366692 2009 BRI3 inhibits amyloid precursor protein processing in a mechanistically distinct manner from its homologue dementia gene BRI2.
19199708 2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).
19114711 2009 Substrate requirements for SPPL2b-dependent regulated intramembrane proteolysis.
19072909 2008 BRI2 as a central protein involved in neurodegeneration.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18753367 2008 BRI2 inhibits amyloid beta-peptide precursor protein processing by interfering with the docking of secretases to the substrate.
18524908 2008 BRI2 (ITM2b) inhibits Abeta deposition in vivo.
18440095 2010 BRI2 homodimerizes with the involvement of intermolecular disulfide bonds.
18282158 2008 Expression of BRI2 mRNA and protein in normal human brain and familial British dementia: its relevance to the pathogenesis of disease.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17965014 2008 Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b.
16612984 2006 Genetic alterations of the BRI2 gene: familial British and Danish dementias.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16091362 2005 Familial Danish dementia: co-existence of Danish and Alzheimer amyloid subunits (ADan AND A{beta}) in the absence of compact plaques.
16027166 2005 BRI2 interacts with amyloid precursor protein (APP) and regulates amyloid beta (Abeta) production.
15983050 2005 The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production.
15968464 2005 Chromosome 13 dementias.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14656991 2004 Axonal transport of British and Danish amyloid peptides via secretory vesicles.
14586629 2004 Expression of BRI, the normal precursor of the amyloid protein of familial British dementia, in human brain.
12903036 2003 [Sequence analysis and expression study of BRI gene in two lung adenocarcinoma cell lines with different metastatic potential].
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12196136 2002 Properties of neurotoxic peptides related to the BRI gene.
12082633 2002 Proapoptotic activity of ITM2B(s), a BH3-only protein induced upon IL-2-deprivation which interacts with Bcl-2.
10931946 2000 Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.
10781099 2000 A decamer duplication in the 3' region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred.
10526337 1999 Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia.
10391242 1999 A stop-codon mutation in the BRI gene associated with familial British dementia.
9795190 1998 cDNA sequence analysis, chromosomal assignment and expression pattern of the gene coding for integral membrane protein 2B.
5466275 1970 Luria testing in demented patients.