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Q5XIE8 (ITM2B_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 68. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Integral membrane protein 2B
Alternative name(s):
Immature BRI2
Short name=imBRI2
Transmembrane protein BRI
Short name=Bri

Cleaved into the following 4 chains:

  1. BRI2, membrane form
    Alternative name(s):
    Mature BRI2
    Short name=mBRI2
  2. BRI2 intracellular domain
    Short name=BRI2 ICD
  3. BRI2C, soluble form
  4. Bri23 peptide
    Short name=Bri2-23
    Alternative name(s):
    ABri23
    C-terminal peptide
    P23 peptide
Gene names
Name:Itm2b
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length266 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

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 By similarity.

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 By similarity.

Bri23 peptide prevents aggregation of APP beta-amyloid protein 42 peptide into toxic oligomers By similarity.

Subunit structure

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 By similarity.

Subcellular location

Integral membrane protein 2B: Golgi apparatus membrane; Single-pass type II membrane protein By similarity. 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 By similarity.

BRI2, membrane form: Cell membrane; Single-pass type II membrane protein By similarity. Endosome membrane; Single-pass type II membrane protein By similarity. 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 By similarity.

Bri23 peptide: Secreted By similarity. Note: Detected in the cerebral spinal fluid (CSF) By similarity.

BRI2C, soluble form: Secreted By similarity.

Post-translational modification

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 By similarity.

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

Sequence similarities

Belongs to the ITM2 family.

Contains 1 BRICHOS domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 266266Integral membrane protein 2B
PRO_0000154824
Chain1 – 243243BRI2, membrane form By similarity
PRO_0000417487
Chain1 – ?BRI2 intracellular domain By similarityPRO_0000417488
Chain? – 243BRI2C, soluble form By similarityPRO_0000417489
Peptide244 – 26623Bri23 peptide By similarity
PRO_0000417490

Regions

Topological domain1 – 5454Cytoplasmic Potential
Transmembrane55 – 7521Helical; Signal-anchor for type II membrane protein; Potential
Topological domain76 – 266191Lumenal Potential
Domain137 – 23195BRICHOS
Region102 – 13433Necessary for interaction with APP and inhibitor effects on APP processing By similarity

Sites

Site243 – 2442Cleavage; by furin By similarity

Amino acid modifications

Glycosylation1701N-linked (GlcNAc...) Potential
Disulfide bond89Interchain By similarity
Disulfide bond164 ↔ 223 By similarity
Disulfide bond248 ↔ 265 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q5XIE8 [UniParc].

Last modified November 23, 2004. Version 1.
Checksum: E3925091C653C449

FASTA26630,314
        10         20         30         40         50         60 
MVKVTFNSAL AQKEAKKDEP KSSEEALIAP PDAVAVDCKD PDDVVPVGQR RAWCWCMCFG 

        70         80         90        100        110        120 
LAFMLAGVIL GGAYLYKYFA LQPDDVYYCG LKYIKDDVIL SEPSADAPAA RYQTIEENIK 

       130        140        150        160        170        180 
IFEEDAVEFI SVPVPEFADS DPANIVHDFN KKLTAYLDLN LDKCYVIPLN TSIVMPPRNL 

       190        200        210        220        230        240 
LELLINIKAG TYLPQSYLIH EHMVITDRIE NVDHLGFFIY RLCHDKETYK LQRRETIRGI 

       250        260 
QKREASNCFT IRHFENKFAV ETLICS 

« Hide

References

[1]"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].
Tissue: Heart.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC083735 mRNA. Translation: AAH83735.1.
RefSeqNP_001006964.1. NM_001006963.1.
UniGeneRn.107335.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid253181. 1 interaction.
MINTMINT-4580553.
STRING10116.ENSRNOP00000023037.

PTM databases

PhosphoSiteQ5XIE8.

Proteomic databases

PaxDbQ5XIE8.
PRIDEQ5XIE8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000023037; ENSRNOP00000023037; ENSRNOG00000016271.
GeneID290364.
KEGGrno:290364.
UCSCRGD:620727. rat.

Organism-specific databases

CTD9445.
RGD620727. Itm2b.

Phylogenomic databases

eggNOGNOG283703.
GeneTreeENSGT00390000005162.
HOGENOMHOG000231259.
HOVERGENHBG059373.
InParanoidQ5XIE8.
OMAVTIRHFE.
OrthoDBEOG70KGQD.
PhylomeDBQ5XIE8.
TreeFamTF317770.

Gene expression databases

GenevestigatorQ5XIE8.

Family and domain databases

InterProIPR007084. BRICHOS_dom.
[Graphical view]
PfamPF04089. BRICHOS. 1 hit.
[Graphical view]
SMARTSM01039. BRICHOS. 1 hit.
[Graphical view]
PROSITEPS50869. BRICHOS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio630989.
PROQ5XIE8.

Entry information

Entry nameITM2B_RAT
AccessionPrimary (citable) accession number: Q5XIE8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2006
Last sequence update: November 23, 2004
Last modified: April 16, 2014
This is version 68 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families