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Protein

Integral membrane protein 2B

Gene

ITM2B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei243 – 2442Cleavage; by furin

GO - Molecular functioni

  • ATP binding Source: Ensembl
  • beta-amyloid binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_75925. Amyloids.

Names & Taxonomyi

Protein namesi
Recommended name:
Integral membrane protein 2B
Alternative name(s):
Immature BRI2
Short name:
imBRI2
Protein E25B
Transmembrane protein BRI
Short name:
Bri
Cleaved into the following 4 chains:
Alternative name(s):
Mature BRI2
Short name:
mBRI2
BRI2 intracellular domain
Short name:
BRI2 ICD
Bri23 peptide
Short name:
Bri2-23
Alternative name(s):
ABri23
C-terminal peptide
P23 peptide
Gene namesi
Name:ITM2B
Synonyms:BRI, BRI2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:6174. ITM2B.

Subcellular locationi

Integral membrane protein 2B :
BRI2, membrane form :
Peptide Bri23 peptide :
  • Secreted

  • Note: Detected in the cerebral spinal fluid (CSF).

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5454CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei55 – 7521Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini76 – 266191LumenalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • endosome membrane Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • Golgi apparatus Source: HPA
  • Golgi-associated vesicle membrane Source: UniProtKB
  • integral component of organelle membrane Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Amyloid, Cell membrane, Endosome, Golgi apparatus, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Cerebral amyloid angiopathy, ITM2B-related 1 (CAA-ITM2B1)

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).

Disease descriptionA 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.

See also OMIM:176500
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti266 – 2661S → SRTVKKNIIEEN in CAA-ITM2B1; amyloid ABri. 3 Publications
VAR_010239
Cerebral amyloid angiopathy, ITM2B-related 2 (CAA-ITM2B2)

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.

Disease descriptionA 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.

See also OMIM:117300
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti266 – 2661S → FNLFLNSQEKHY in CAA-ITM2B2; amyloid ADan; colocalizes with APP beta-amyloid protein 42 in parenchymal and vascular lesions; interacts with APP beta-amyloid 42; oligomerizes and is subjected to disulfide bond formation; undergoes cyclic pyroglutamate formation on the N-terminus Gln residues and is further proteolytically cleaved in the cerebral cortex. 3 Publications
VAR_010240
Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities (RDGCA)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn autosomal dominant retinal dystrophy characterized by inner retinal dysfunction in association with ganglion cell abnormalities. Clinical features include mild photophobia, progressive loss of central vision, night blindness, and hyperreflectivity of nerve and ganglion cell layers.

See also OMIM:616079
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti261 – 2611E → A in RDGCA. 1 Publication
VAR_072434

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi60 – 601G → V: Reduces strongly intramembrane cleavage by SPPL2B. 1 Publication
Mutagenesisi170 – 1701N → A: Accumulates in intracellular compartments. Does not inhibit furin, ADAM10 and SPPL2A extracellular proteolytic processing activity. 1 Publication
Mutagenesisi243 – 2442RE → AA: Inhibits cleavage by furin. Does not prevent ADAM10 shedding. 2 Publications

Keywords - Diseasei

Amyloidosis, Deafness, Disease mutation, Neurodegeneration

Organism-specific databases

MIMi117300. phenotype.
176500. phenotype.
616079. phenotype.
Orphaneti97345. Familial dementia, British type.
97346. Familial dementia, Danish type.
397758. Retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies.
PharmGKBiPA29971.

Polymorphism and mutation databases

BioMutaiITM2B.
DMDMi12643343.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 243BRI2C, soluble formPRO_0000417466
Chaini1 – 266266Integral membrane protein 2BPRO_0000045840Add
BLAST
Chaini1 – 243243BRI2, membrane formPRO_0000417464Add
BLAST
Chaini1 – ?BRI2 intracellular domainPRO_0000417465
Peptidei244 – 26623Bri23 peptidePRO_0000016545Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi89 – 89Interchain
Disulfide bondi164 ↔ 223By similarity
Glycosylationi170 – 1701N-linked (GlcNAc...)1 Publication
Disulfide bondi248 ↔ 265Interchain (between ADan peptide variants)

Post-translational modificationi

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.
Glycosylation at Asn-170 is important for cell surface localization, but doesn't affect furin- and ADAM10-induced proteolytic processing.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9Y287.
PaxDbiQ9Y287.
PeptideAtlasiQ9Y287.
PRIDEiQ9Y287.

PTM databases

PhosphoSiteiQ9Y287.

Expressioni

Tissue specificityi

Ubiquitous. Expressed in brain.

Gene expression databases

BgeeiQ9Y287.
CleanExiHS_ITM2B.
ExpressionAtlasiQ9Y287. baseline and differential.
GenevisibleiQ9Y287. HS.

Organism-specific databases

HPAiHPA029292.

Interactioni

Subunit structurei

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 40.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CCDC155Q8N6L03EBI-2866431,EBI-749265
NAALADL2Q58DX53EBI-2866431,EBI-10178964
SYNE4Q8N2053EBI-2866431,EBI-7131783

Protein-protein interaction databases

BioGridi114835. 25 interactions.
IntActiQ9Y287. 10 interactions.
STRINGi9606.ENSP00000367828.

Structurei

3D structure databases

ProteinModelPortaliQ9Y287.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini137 – 23195BRICHOSPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni102 – 13433Necessary for interaction with APP and inhibitor effects on APP processingAdd
BLAST

Sequence similaritiesi

Belongs to the ITM2 family.Curated
Contains 1 BRICHOS domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG283703.
GeneTreeiENSGT00390000005162.
HOGENOMiHOG000231259.
HOVERGENiHBG059373.
InParanoidiQ9Y287.
KOiK18264.
OMAiVTIRHFE.
OrthoDBiEOG70KGQD.
PhylomeDBiQ9Y287.
TreeFamiTF317770.

Family and domain databases

InterProiIPR007084. BRICHOS_dom.
[Graphical view]
PfamiPF04089. BRICHOS. 1 hit.
[Graphical view]
SMARTiSM01039. BRICHOS. 1 hit.
[Graphical view]
PROSITEiPS50869. BRICHOS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y287-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVKVTFNSAL AQKEAKKDEP KSGEEALIIP PDAVAVDCKD PDDVVPVGQR
60 70 80 90 100
RAWCWCMCFG LAFMLAGVIL GGAYLYKYFA LQPDDVYYCG IKYIKDDVIL
110 120 130 140 150
NEPSADAPAA LYQTIEENIK IFEEEEVEFI SVPVPEFADS DPANIVHDFN
160 170 180 190 200
KKLTAYLDLN LDKCYVIPLN TSIVMPPRNL LELLINIKAG TYLPQSYLIH
210 220 230 240 250
EHMVITDRIE NIDHLGFFIY RLCHDKETYK LQRRETIKGI QKREASNCFA
260
IRHFENKFAV ETLICS
Length:266
Mass (Da):30,338
Last modified:November 1, 1999 - v1
Checksum:i3A7D8CA259F1F627
GO
Isoform 2 (identifier: Q9Y287-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     83-188: Missing.

Note: No experimental confirmation available.
Show »
Length:160
Mass (Da):18,283
Checksum:i1945A235CC75B5C3
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti15 – 151A → T.2 Publications
Corresponds to variant rs11556905 [ dbSNP | Ensembl ].
VAR_071047
Natural varianti261 – 2611E → A in RDGCA. 1 Publication
VAR_072434
Natural varianti266 – 2661S → FNLFLNSQEKHY in CAA-ITM2B2; amyloid ADan; colocalizes with APP beta-amyloid protein 42 in parenchymal and vascular lesions; interacts with APP beta-amyloid 42; oligomerizes and is subjected to disulfide bond formation; undergoes cyclic pyroglutamate formation on the N-terminus Gln residues and is further proteolytically cleaved in the cerebral cortex. 3 Publications
VAR_010240
Natural varianti266 – 2661S → SRTVKKNIIEEN in CAA-ITM2B1; amyloid ABri. 3 Publications
VAR_010239

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei83 – 188106Missing in isoform 2. CuratedVSP_055326Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF152462 mRNA. Translation: AAD45280.1.
AF246221 mRNA. Translation: AAF66130.1.
AF136973 mRNA. Translation: AAG49434.1.
AF092128 mRNA. Translation: AAD40370.1.
BT006863 mRNA. Translation: AAP35509.1.
AY341247 Genomic DNA. Translation: AAP88930.1.
CH471075 Genomic DNA. Translation: EAX08789.1.
CH471075 Genomic DNA. Translation: EAX08790.1.
BC000554 mRNA. Translation: AAH00554.1.
BC016148 mRNA. Translation: AAH16148.1.
CCDSiCCDS9409.1. [Q9Y287-1]
RefSeqiNP_068839.1. NM_021999.4. [Q9Y287-1]
UniGeneiHs.643683.

Genome annotation databases

EnsembliENST00000378549; ENSP00000367811; ENSG00000136156. [Q9Y287-2]
ENST00000378565; ENSP00000367828; ENSG00000136156. [Q9Y287-1]
GeneIDi9445.
KEGGihsa:9445.
UCSCiuc001vbz.3. human. [Q9Y287-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF152462 mRNA. Translation: AAD45280.1.
AF246221 mRNA. Translation: AAF66130.1.
AF136973 mRNA. Translation: AAG49434.1.
AF092128 mRNA. Translation: AAD40370.1.
BT006863 mRNA. Translation: AAP35509.1.
AY341247 Genomic DNA. Translation: AAP88930.1.
CH471075 Genomic DNA. Translation: EAX08789.1.
CH471075 Genomic DNA. Translation: EAX08790.1.
BC000554 mRNA. Translation: AAH00554.1.
BC016148 mRNA. Translation: AAH16148.1.
CCDSiCCDS9409.1. [Q9Y287-1]
RefSeqiNP_068839.1. NM_021999.4. [Q9Y287-1]
UniGeneiHs.643683.

3D structure databases

ProteinModelPortaliQ9Y287.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114835. 25 interactions.
IntActiQ9Y287. 10 interactions.
STRINGi9606.ENSP00000367828.

PTM databases

PhosphoSiteiQ9Y287.

Polymorphism and mutation databases

BioMutaiITM2B.
DMDMi12643343.

Proteomic databases

MaxQBiQ9Y287.
PaxDbiQ9Y287.
PeptideAtlasiQ9Y287.
PRIDEiQ9Y287.

Protocols and materials databases

DNASUi9445.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000378549; ENSP00000367811; ENSG00000136156. [Q9Y287-2]
ENST00000378565; ENSP00000367828; ENSG00000136156. [Q9Y287-1]
GeneIDi9445.
KEGGihsa:9445.
UCSCiuc001vbz.3. human. [Q9Y287-1]

Organism-specific databases

CTDi9445.
GeneCardsiGC13P048807.
HGNCiHGNC:6174. ITM2B.
HPAiHPA029292.
MIMi117300. phenotype.
176500. phenotype.
603904. gene.
616079. phenotype.
neXtProtiNX_Q9Y287.
Orphaneti97345. Familial dementia, British type.
97346. Familial dementia, Danish type.
397758. Retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies.
PharmGKBiPA29971.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG283703.
GeneTreeiENSGT00390000005162.
HOGENOMiHOG000231259.
HOVERGENiHBG059373.
InParanoidiQ9Y287.
KOiK18264.
OMAiVTIRHFE.
OrthoDBiEOG70KGQD.
PhylomeDBiQ9Y287.
TreeFamiTF317770.

Enzyme and pathway databases

ReactomeiREACT_75925. Amyloids.

Miscellaneous databases

ChiTaRSiITM2B. human.
GeneWikiiITM2B.
GenomeRNAii9445.
NextBioi35380.
PROiQ9Y287.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y287.
CleanExiHS_ITM2B.
ExpressionAtlasiQ9Y287. baseline and differential.
GenevisibleiQ9Y287. HS.

Family and domain databases

InterProiIPR007084. BRICHOS_dom.
[Graphical view]
PfamiPF04089. BRICHOS. 1 hit.
[Graphical view]
SMARTiSM01039. BRICHOS. 1 hit.
[Graphical view]
PROSITEiPS50869. BRICHOS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A stop-codon mutation in the BRI gene associated with familial British dementia."
    Vidal R., Frangione B., Rostagno A., Mead S., Revesz T., Plant G., Ghiso J.
    Nature 399:776-781(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CAA-ITM2B1 ARG-THR-VAL-LYS-LYS-ASN-ILE-ILE-GLU-GLU-ASN-266 INS.
    Tissue: Pituitary.
  2. "A decamer duplication in the 3' region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred."
    Vidal R., Revesz T., Rostagno A., Kim E., Holton J.L., Bek T., Bojsen-Moeller M., Braendgaard H., Plant G., Ghiso J., Frangione B.
    Proc. Natl. Acad. Sci. U.S.A. 97:4920-4925(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CAA-ITM2B2 SER-266 DELINS PHE-ASN-LEU-PHE-LEU-ASN-SER-GLN-GLU-LYS-HIS-TYR.
  3. "A novel gene expressed in human adrenal gland."
    Ren S., Shi J., Huang C., Jiang C., Li Y., Zhou J., Yu Y., Xu S., Wang Y., Fu G., Chen Z., Han Z.
    Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Adrenal gland.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Pituitary.
  5. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-15.
  6. NIEHS SNPs program
    Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-15.
    Tissue: Brain and Uterus.
  9. "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."
    Audo I., Bujakowska K., Orhan E., El Shamieh S., Sennlaub F., Guillonneau X., Antonio A., Michiels C., Lancelot M.E., Letexier M., Saraiva J.P., Nguyen H., Luu T.D., Leveillard T., Poch O., Dollfus H., Paques M., Goureau O.
    , Mohand-Said S., Bhattacharya S.S., Sahel J.A., Zeitz C.
    Hum. Mol. Genet. 23:491-501(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN RDGCA, VARIANT RDGCA ALA-261.
  10. "Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia."
    Kim S.H., Wang R., Gordon D.J., Bass J., Steiner D.F., Lynn D.G., Thinakaran G., Meredith S.C., Sisodia S.S.
    Nat. Neurosci. 2:984-988(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANT CAA-ITM2B1 ARG-THR-VAL-LYS-LYS-ASN-ILE-ILE-GLU-GLU-ASN-266 INS, TOPOLOGY, CLEAVAGE BY FURIN, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
  11. "Axonal transport of British and Danish amyloid peptides via secretory vesicles."
    Choi S.I., Vidal R., Frangione B., Levy E.
    FASEB J. 18:373-375(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TOPOLOGY, PROTEOLYTIC CLEAVAGE, CHARACTERIZATION OF VARIANTS CAA-ITM2B1 ARG-THR-VAL-LYS-LYS-ASN-ILE-ILE-GLU-GLU-ASN-266 INS AND CAA-ITM2B2 SER-266 DELINS PHE-ASN-LEU-PHE-LEU-ASN-SER-GLN-GLU-LYS-HIS-TYR, SUBCELLULAR LOCATION.
  12. "The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production."
    Matsuda S., Giliberto L., Matsuda Y., Davies P., McGowan E., Pickford F., Ghiso J., Frangione B., D'Adamio L.
    J. Biol. Chem. 280:28912-28916(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH APP.
  13. "BRI2 interacts with amyloid precursor protein (APP) and regulates amyloid beta (Abeta) production."
    Fotinopoulou A., Tsachaki M., Vlavaki M., Poulopoulos A., Rostagno A., Frangione B., Ghiso J., Efthimiopoulos S.
    J. Biol. Chem. 280:30768-30772(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH APP.
  14. "Familial Danish dementia: co-existence of Danish and Alzheimer amyloid subunits (ADan AND A{beta}) in the absence of compact plaques."
    Tomidokoro Y., Lashley T., Rostagno A., Neubert T.A., Bojsen-Moller M., Braendgaard H., Plant G., Holton J., Frangione B., Revesz T., Ghiso J.
    J. Biol. Chem. 280:36883-36894(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANT CAA-ITM2B2 SER-266 DELINS PHE-ASN-LEU-PHE-LEU-ASN-SER-GLN-GLU-LYS-HIS-TYR.
  15. "Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b."
    Martin L., Fluhrer R., Reiss K., Kremmer E., Saftig P., Haass C.
    J. Biol. Chem. 283:1644-1652(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TOPOLOGY, CLEAVAGE BY ADAM10; FURIN; SPPL2A AND SPPL2B, INTERACTION WITH SPPL2A AND SPPL2B, MUTAGENESIS OF 243-ARG-GLU-244.
  16. Cited for: FUNCTION OF SECRETED BRI23 PEPTIDE, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
  17. "BRI2 inhibits amyloid beta-peptide precursor protein processing by interfering with the docking of secretases to the substrate."
    Matsuda S., Giliberto L., Matsuda Y., McGowan E.M., D'Adamio L.
    J. Neurosci. 28:8668-8676(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  18. "Substrate requirements for SPPL2b-dependent regulated intramembrane proteolysis."
    Martin L., Fluhrer R., Haass C.
    J. Biol. Chem. 284:5662-5670(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY ADAM10; FURIN AND SPPL2B, SUBCELLULAR LOCATION.
  19. "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."
    Peng S., Fitzen M., Jornvall H., Johansson J.
    Biochem. Biophys. Res. Commun. 393:356-361(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF SECRETED BRI23 PEPTIDE, SUBUNIT, INTERACTION WITH APP BETA-AMYLOID PROTEIN 40, DISULFIDE BOND, IDENTIFICATION BY MASS SPECTROMETRY.
  20. "BRI2 homodimerizes with the involvement of intermolecular disulfide bonds."
    Tsachaki M., Ghiso J., Rostagno A., Efthimiopoulos S.
    Neurobiol. Aging 31:88-98(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, SUBUNIT, DISULFIDE BONDS.
  21. "Glycosylation of BRI2 on asparagine 170 is involved in its trafficking to the cell surface but not in its processing by furin or ADAM10."
    Tsachaki M., Serlidaki D., Fetani A., Zarkou V., Rozani I., Ghiso J., Efthimiopoulos S.
    Glycobiology 21:1382-1388(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY ADAM10; FURIN AND SPPL2B, GLYCOSYLATION AT ASN-170, SUBCELLULAR LOCATION, MUTAGENESIS OF ASN-170.
  22. "Maturation of BRI2 generates a specific inhibitor that reduces APP processing at the plasma membrane and in endocytic vesicles."
    Matsuda S., Matsuda Y., Snapp E.L., D'Adamio L.
    Neurobiol. Aging 32:1400-1408(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF MBRI2 IN APP PROCESSING INHIBITION, INTERACTION WITH APP AMYLOID BETA A4 AND APP C99, PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, MUTAGENESIS OF 243-ARG-GLU-244.
  23. "beta- but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia."
    Tamayev R., Matsuda S., Arancio O., D'Adamio L.
    EMBO Mol. Med. 4:171-179(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF MBRI2 IN APP PROCESSING INHIBITION, INTERACTION WITH APP AMYLOID BETA A4 AND APP C99.
  24. "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)."
    Fluhrer R., Martin L., Klier B., Haug-Kroper M., Grammer G., Nuscher B., Haass C.
    J. Biol. Chem. 287:5156-5163(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY SPPL2A AND SPPL2B, MUTAGENESIS OF GLY-60.

Entry informationi

Entry nameiITM2B_HUMAN
AccessioniPrimary (citable) accession number: Q9Y287
Secondary accession number(s): Q5W0A3, Q96B24, Q9NYH1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: November 1, 1999
Last modified: June 24, 2015
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.