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 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr13:48,233,203-48,261,388)mRNA (may differ from genome)Protein (160 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblExonPrimerGeneCardsHGNCLynx
MGIneXtProtPubMedReactomeStanford SOURCEUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  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/";

-  MalaCards Disease Associations
  MalaCards Gene Search: ITM2B
Diseases sorted by gene-association score: retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities* (1731), dementia, familial british* (1380), dementia, familial danish* (1372), cerebral amyloid angiopathy (27), dementia (25), functional diarrhea (17), variola minor (11), sick building syndrome (6), pleomorphic lipoma (6), alzheimer disease mitochondrial (5), alzheimer disease (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 446.74 RPKM in Whole Blood
Total median expression: 11221.44 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -70.90158-0.449 Picture PostScript Text
3' UTR -20.00164-0.122 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007084 - BRICHOS_dom

Pfam Domains:
PF04089 - BRICHOS domain

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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
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:0044267 cellular protein metabolic process
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component:
GO:0000139 Golgi membrane
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005768 endosome
GO:0005794 Golgi apparatus
GO:0005886 plasma membrane
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030660 Golgi-associated vesicle membrane
GO:0031301 integral component of organelle membrane
GO:0043231 intracellular membrane-bounded organelle
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  BC018053 - Homo sapiens cDNA clone IMAGE:4815700, containing frame-shift errors.
AF092128 - Homo sapiens putative transmembrane protein E3-16 mRNA, complete cds.
AF136973 - Homo sapiens putative transmembrane protein E3-16 mRNA, complete cds.
AF152462 - Homo sapiens transmembrane protein BRI (BRI) mRNA, complete cds.
AF246221 - Homo sapiens transmembrane protein BRI mRNA, complete cds.
BC016148 - Homo sapiens integral membrane protein 2B, mRNA (cDNA clone MGC:10219 IMAGE:3912066), complete cds.
AK027411 - Homo sapiens cDNA FLJ14505 fis, clone NT2RM1000355, highly similar to Homo sapiens transmembrane protein BRI mRNA.
AK000503 - Homo sapiens cDNA FLJ20496 fis, clone KAT08729.
AK130048 - Homo sapiens cDNA FLJ26538 fis, clone KDN09296, highly similar to Integral membrane protein 2B.
BC000554 - Homo sapiens integral membrane protein 2B, mRNA (cDNA clone MGC:1034 IMAGE:3163436), complete cds.
AF086918 - Homo sapiens E3-16 mRNA, complete cds.
AB527639 - Synthetic construct DNA, clone: pF1KB5464, Homo sapiens ITM2B gene for integral membrane protein 2B, without stop codon, in Flexi system.
DQ890591 - Synthetic construct clone IMAGE:100003221; FLH164282.01X; RZPDo839E08162D integral membrane protein 2B (ITM2B) gene, encodes complete protein.
DQ893759 - Synthetic construct Homo sapiens clone IMAGE:100008219; FLH164278.01L; RZPDo839E08161D integral membrane protein 2B (ITM2B) gene, encodes complete protein.
CU674270 - Synthetic construct Homo sapiens gateway clone IMAGE:100016934 5' read ITM2B mRNA.
KJ898023 - Synthetic construct Homo sapiens clone ccsbBroadEn_07417 ITM2B gene, encodes complete protein.
KJ898024 - Synthetic construct Homo sapiens clone ccsbBroadEn_07418 ITM2B gene, encodes complete protein.
BT006863 - Homo sapiens integral membrane protein 2B mRNA, complete cds.
GQ891384 - Homo sapiens clone HEL-S-179n epididymis secretory sperm binding protein mRNA, complete cds.
JD056175 - Sequence 37199 from Patent EP1572962.
JD069299 - Sequence 50323 from Patent EP1572962.
JD519010 - Sequence 500034 from Patent EP1572962.
JD125189 - Sequence 106213 from Patent EP1572962.
JD394669 - Sequence 375693 from Patent EP1572962.
BX537657 - Homo sapiens mRNA; cDNA DKFZp686I1394 (from clone DKFZp686I1394).
LF210157 - JP 2014500723-A/17660: Polycomb-Associated Non-Coding RNAs.
MA445734 - JP 2018138019-A/17660: Polycomb-Associated Non-Coding RNAs.
LF335182 - JP 2014500723-A/142685: Polycomb-Associated Non-Coding RNAs.
MA570759 - JP 2018138019-A/142685: Polycomb-Associated Non-Coding RNAs.
LF335181 - JP 2014500723-A/142684: Polycomb-Associated Non-Coding RNAs.
MA570758 - JP 2018138019-A/142684: Polycomb-Associated Non-Coding RNAs.
LF335180 - JP 2014500723-A/142683: Polycomb-Associated Non-Coding RNAs.
MA570757 - JP 2018138019-A/142683: Polycomb-Associated Non-Coding RNAs.
LF335179 - JP 2014500723-A/142682: Polycomb-Associated Non-Coding RNAs.
MA570756 - JP 2018138019-A/142682: Polycomb-Associated Non-Coding RNAs.
JD025649 - Sequence 6673 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9Y287 (Reactome details) participates in the following event(s):

R-HSA-977225 Amyloid fiber formation
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: BC016148, BRI, BRI2, ITM2B_HUMAN, Q9NYH1, Q9Y287, uc058wyb.1
UCSC ID: uc058wyb.1
RefSeq Accession: NM_021999
Protein: Q9Y287 (aka ITM2B_HUMAN)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.