SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q9Y287

- ITM2B_HUMAN

UniProt

Q9Y287 - ITM2B_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein
Integral membrane protein 2B
Gene
ITM2B, BRI, BRI2
Organism
Homo sapiens (Human)
Status
Reviewed - 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.8 Publications
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 42.8 Publications
Bri23 peptide prevents aggregation of APP beta-amyloid protein 42 peptide into toxic oligomers.8 Publications

Sites

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

GO - Molecular functioni

  1. ATP binding Source: Ensembl
  2. beta-amyloid binding Source: BHF-UCL
  3. protein binding Source: UniProtKB

GO - Biological processi

  1. extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  2. negative regulation of amyloid precursor protein biosynthetic process Source: UniProtKB
  3. nervous system development Source: ProtInc
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: Chromosome 13

Organism-specific databases

HGNCiHGNC:6174. ITM2B.

Subcellular locationi

Chain 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.8 Publications
Chain 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.8 Publications
Bri23 peptide : Secreted
Note: Detected in the cerebral spinal fluid (CSF).8 Publications
Chain BRI2C, soluble form : Secreted 8 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5454Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei55 – 7521Helical; Signal-anchor for type II membrane protein; Reviewed prediction
Add
BLAST
Topological domaini76 – 266191Lumenal Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. Golgi apparatus Source: HPA
  2. Golgi-associated vesicle membrane Source: UniProtKB
  3. endosome membrane Source: UniProtKB-SubCell
  4. extracellular region Source: Reactome
  5. extracellular space Source: UniProtKB
  6. extracellular vesicular exosome Source: UniProt
  7. integral component of membrane Source: UniProtKB-KW
  8. integral component of organelle membrane Source: UniProtKB
  9. intracellular membrane-bounded organelle Source: HPA
  10. 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) [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: 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 (1 Publication). ABri accumulates in the brain and produces amyloid fibrils responsible for neuronal dysfunction and dementia. ABri peptide variant forms fibrils in vitro (1 Publication).3 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti266 – 2661S → SRTVKKNIIEEN in CAA-ITM2B1; amyloid ABri.
VAR_010239
Cerebral amyloid angiopathy, ITM2B-related 2 (CAA-ITM2B2) [MIM:117300]: 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: 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 (1 Publication). 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.3 Publications
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

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi60 – 601G → V: Reduces strongly intramembrane cleavage by SPPL2B. 3 Publications
Mutagenesisi170 – 1701N → A: Accumulates in intracellular compartments. Does not inhibit furin, ADAM10 and SPPL2A extracellular proteolytic processing activity. 3 Publications
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.
Orphaneti97345. Familial dementia, British type.
97346. Familial dementia, Danish type.
PharmGKBiPA29971.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 243BRI2C, soluble formPRO_0000417466
Chaini1 – 266266Integral membrane protein 2B
PRO_0000045840Add
BLAST
Chaini1 – 243243BRI2, membrane form
PRO_0000417464Add
BLAST
Chaini1 – ?BRI2 intracellular domainPRO_0000417465
Peptidei244 – 26623Bri23 peptide
PRO_0000016545Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi89 – 89Interchain2 Publications
Disulfide bondi164 ↔ 223 By similarity
Glycosylationi170 – 1701N-linked (GlcNAc...)1 Publication
Disulfide bondi248 ↔ 265Interchain (between ADan peptide variants)2 Publications

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

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

ArrayExpressiQ9Y287.
BgeeiQ9Y287.
CleanExiHS_ITM2B.
GenevestigatoriQ9Y287.

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

Protein-protein interaction databases

BioGridi114835. 4 interactions.
IntActiQ9Y287. 7 interactions.
STRINGi9606.ENSP00000367828.

Structurei

3D structure databases

ProteinModelPortaliQ9Y287.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini137 – 23195BRICHOS
Add
BLAST

Region

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

Sequence similaritiesi

Belongs to the ITM2 family.
Contains 1 BRICHOS domain.

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG283703.
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. Align

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

MVKVTFNSAL AQKEAKKDEP KSGEEALIIP PDAVAVDCKD PDDVVPVGQR    50
RAWCWCMCFG LAFMLAGVIL GGAYLYKYFA LQPDDVYYCG IKYIKDDVIL 100
NEPSADAPAA LYQTIEENIK IFEEEEVEFI SVPVPEFADS DPANIVHDFN 150
KKLTAYLDLN LDKCYVIPLN TSIVMPPRNL LELLINIKAG TYLPQSYLIH 200
EHMVITDRIE NIDHLGFFIY RLCHDKETYK LQRRETIKGI QKREASNCFA 250
IRHFENKFAV ETLICS 266
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 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.
VAR_010239

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei83 – 188106Missing in isoform 2.
VSP_055326Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGeneiHs.643683.

Genome annotation databases

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

Polymorphism databases

DMDMi12643343.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS9409.1. [Q9Y287-1 ]
RefSeqi NP_068839.1. NM_021999.4.
UniGenei Hs.643683.

3D structure databases

ProteinModelPortali Q9Y287.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114835. 4 interactions.
IntActi Q9Y287. 7 interactions.
STRINGi 9606.ENSP00000367828.

PTM databases

PhosphoSitei Q9Y287.

Polymorphism databases

DMDMi 12643343.

Proteomic databases

MaxQBi Q9Y287.
PaxDbi Q9Y287.
PeptideAtlasi Q9Y287.
PRIDEi Q9Y287.

Protocols and materials databases

DNASUi 9445.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000378549 ; ENSP00000367811 ; ENSG00000136156 .
ENST00000378565 ; ENSP00000367828 ; ENSG00000136156 .
GeneIDi 9445.
KEGGi hsa:9445.
UCSCi uc001vbz.3. human. [Q9Y287-1 ]

Organism-specific databases

CTDi 9445.
GeneCardsi GC13P048807.
HGNCi HGNC:6174. ITM2B.
HPAi HPA029292.
MIMi 117300. phenotype.
176500. phenotype.
603904. gene.
neXtProti NX_Q9Y287.
Orphaneti 97345. Familial dementia, British type.
97346. Familial dementia, Danish type.
PharmGKBi PA29971.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG283703.
HOGENOMi HOG000231259.
HOVERGENi HBG059373.
InParanoidi Q9Y287.
KOi K18264.
OMAi VTIRHFE.
OrthoDBi EOG70KGQD.
PhylomeDBi Q9Y287.
TreeFami TF317770.

Enzyme and pathway databases

Reactomei REACT_75925. Amyloids.

Miscellaneous databases

ChiTaRSi ITM2B. human.
GeneWikii ITM2B.
GenomeRNAii 9445.
NextBioi 35380.
PROi Q9Y287.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9Y287.
Bgeei Q9Y287.
CleanExi HS_ITM2B.
Genevestigatori Q9Y287.

Family and domain databases

InterProi IPR007084. BRICHOS_dom.
[Graphical view ]
Pfami PF04089. BRICHOS. 1 hit.
[Graphical view ]
SMARTi SM01039. BRICHOS. 1 hit.
[Graphical view ]
PROSITEi PS50869. BRICHOS. 1 hit.
[Graphical view ]
ProtoNeti Search...

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. "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.
  10. "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.
  11. "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.
  12. "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.
  13. "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.
  14. "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.
  15. Cited for: FUNCTION OF SECRETED BRI23 PEPTIDE, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
  16. "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.
  17. "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.
  18. "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.
  19. "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.
  20. "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.
  21. "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.
  22. "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.
  23. "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: September 3, 2014
This is version 125 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