ITM2B integral membrane protein 2B [Homo sapiens (human)] - Gene

Summary

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Official Symbol: ITM2Bprovided by HGNC
Official Full Name: integral membrane protein 2Bprovided by HGNC
Primary source: HGNC:6174
Locus tag: RP11-196P14.1
See related: Ensembl:ENSG00000136156; HPRD:04878; MIM:603904; Vega:OTTHUMG00000016894
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BRI; FBD; ABRI; BRI2; E25B; E3-16; imBRI2; BRICD2B
Summary: 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]

Genomic context

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Location :: 13q14.3

Sequence :: Chromosome: 13; NC_000013.10 (48807274..48836232)

See ITM2B in Epigenomics, MapViewer

Chromosome 13 - NC_000013.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

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.
Title: Increased AβPP processing in familial Danish dementia patients.
BRI2 is a specific inhibitor that reduces access of secretase to amyloid-betaprecursor protein (APP) in intracellular compartments where APP is normally processed.
Title: Maturation of BRI2 generates a specific inhibitor that reduces APP processing at the plasma membrane and in endocytic vesicles.
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.
Title: Glycosylation of BRI2 on asparagine 170 is involved in its trafficking to the cell surface but not in its processing by furin or ADAM10.
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).
Title: The α-helical content of the transmembrane domain of the British dementia protein-2 (Bri2) determines its processing by signal peptide peptidase-like 2b (SPPL2b).
BRI2 protein regulates beta-amyloid degradation by increasing levels of secreted insulin-degrading enzyme (IDE).
Title: BRI2 protein regulates β-amyloid degradation by increasing levels of secreted insulin-degrading enzyme (IDE).
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.
Title: APP heterozygosity averts memory deficit in knockin mice expressing the Danish dementia BRI2 mutant.
Decreased cerebrospinal fluid levels of Bri2-23, a peptide cleaved from Bri2, significantly associates with multiple scleerosis patients with cerebellar dysfunction and cognition impairment.
Title: Bri2-23 is a potential cerebrospinal fluid biomarker in multiple sclerosis.
The British mutation drastically reduces expression of mature BRI2 in both knock-in mice and the brains of familial British dementia patients.
Title: Memory deficits due to familial British dementia BRI2 mutation are caused by loss of BRI2 function rather than amyloidosis.
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.
Title: BRI2 homodimerizes with the involvement of intermolecular disulfide bonds.
These data suggest a model for how the processing of Bri2 and APP are interrelated.
Title: 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.

Submit: New GeneRIF Correction See all (22)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Env, gp160, envelope glycoprotein	env	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	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
Q9Y287	P05067	APP	HPRD	PubMed
Q9Y287	P10415	BCL2	HPRD	PubMed
BioGRID:114835	BioGRID:107068	BCL2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114835	BioGRID:112171	RYK	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114835	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114835	BioGRID:1205544	env	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Amyloids, organism-specific biosystem (from REACTOME)
Amyloids, organism-specific biosystemAmyloid is a term used to describe typically extracellular deposits of aggregated proteins, sometimes known as plaques. Abnormal accumulation of amyloid is amyloidosis, a term associated with disease...
Disease, organism-specific biosystem (from REACTOME)
Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...

General gene information

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Markers

RH44780 (e-PCR)
- UniSTS:57353

D13S1155 (e-PCR)
- UniSTS:4891

A002O26 (e-PCR)
- UniSTS:64356

SHGC-34192 (e-PCR)
- UniSTS:450

RH44653 (e-PCR)
- UniSTS:64709

D13S841E (e-PCR)
- UniSTS:151516

D13S864E (e-PCR)
- UniSTS:151526

Genotypes

See ITM2B SNP Geneview Report
See ITM2B SNP Genotype Report
See ITM2B SNP Variation Viewer Report

Homology

Homologs of the ITM2B gene: The ITM2B gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
beta-amyloid binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
apoptotic process	IEA Inferred from Electronic Annotation more info
induction of apoptosis	IEA Inferred from Electronic Annotation more info
negative regulation of amyloid precursor protein biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
nervous system development	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
Golgi apparatus	IDA Inferred from Direct Assay more info
Golgi-associated vesicle membrane	IDA Inferred from Direct Assay more info	PubMed
endosome membrane	IEA Inferred from Electronic Annotation more info
extracellular region	TAS Traceable Author Statement more info
extracellular space	IDA Inferred from Direct Assay more info	PubMed
integral to organelle membrane	IDA Inferred from Direct Assay more info	PubMed
intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
nucleus	IDA Inferred from Direct Assay more info
plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: integral membrane protein 2B

Names: integral membrane protein 2B; immature BRI2; ABri/ADan amyloid peptide; transmembrane protein BRI; BRICHOS domain containing 2B

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013069.1 RefSeqGene

Range

5001..33959

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_021999.4 → NP_068839.1 integral membrane protein 2B

Status: REVIEWED

Source sequence(s)

AF136973, AF152462, AK130048, DA087198

Consensus CDS

CCDS9409.1

UniProtKB/TrEMBL

Q5W0A3

UniProtKB/Swiss-Prot

Q9Y287

Related

ENSP00000367828, OTTHUMP00000018394, ENST00000378565, OTTHUMT00000044870

Conserved Domains (1) summary

pfam04089
Location:138 – 231
Blast Score: 305

BRICHOS; BRICHOS domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000013.10 Reference GRCh37.p10 Primary Assembly

Range

48807274..48836232

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000145.1 Alternate HuRef

Range

29599469..29628426

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018924.1 Alternate CHM1_1.0

Range

29750384..29779347

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01051004.1 (15125..44082)	None
genomic	AL139322.13 (65368..94326)	None
genomic	AMYH01005101.1 (22..28985)	None
genomic	AY341247.1	AAP88930.1
genomic	CH471075.1	EAX08788.1
		EAX08789.1
		EAX08790.1
		EAX08791.1
mRNA	AF086918.1	AAP97148.1
mRNA	AF092128.1	AAD40370.1
mRNA	AF136973.1	AAG49434.1
mRNA	AF152462.1	AAD45280.1
mRNA	AF246221.1	AAF66130.1
mRNA	AK000503.1	BAA91210.1
mRNA	AK027411.1	None
mRNA	AK130048.1	None
mRNA	BC000554.2	AAH00554.1
mRNA	BC016148.1	AAH16148.1
mRNA	BC018053.1	None
mRNA	BT006863.1	AAP35509.1
mRNA	DA087198.1	None
other-genetic	DQ890591.2	ABM92208.1
other-genetic	DQ893759.2	ABM84685.1