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Protein

Integral membrane protein 2B

Gene

Itm2b

Organism
Mus musculus (Mouse)
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 (By similarity).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

GO - Molecular functioni

  • ATP binding Source: MGI
  • beta-amyloid binding Source: MGI

GO - Biological processi

Complete GO annotation...

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1309517. Itm2b.

Subcellular locationi

Integral membrane protein 2B :
  • Golgi apparatus membrane By similarity; 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 By similarity; Single-pass type II membrane protein By similarity
  • Endosome membrane By similarity; 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
Peptide Bri23 peptide :
  • Secreted By similarity

  • Note: Detected in the cerebral spinal fluid (CSF).By similarity
BRI2C, soluble form :
  • Secreted By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 54CytoplasmicSequence analysisAdd BLAST54
Transmembranei55 – 75Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini76 – 266LumenalSequence analysisAdd BLAST191

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Golgi apparatus, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000417473? – 243BRI2C, soluble formBy similarity
ChainiPRO_00001548221 – 266Integral membrane protein 2BAdd BLAST266
ChainiPRO_00004174711 – 243BRI2, membrane formBy similarityAdd BLAST243
ChainiPRO_00004174721 – ?BRI2 intracellular domainBy similarity
PeptideiPRO_0000417474244 – 266Bri23 peptideBy similarityAdd BLAST23

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi89InterchainBy similarity
Disulfide bondi164 ↔ 223By similarity
Glycosylationi170N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi248 ↔ 265By similarity

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei243 – 244Cleavage; by furinBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO89051.
MaxQBiO89051.
PaxDbiO89051.
PeptideAtlasiO89051.
PRIDEiO89051.

PTM databases

iPTMnetiO89051.
PhosphoSitePlusiO89051.
SwissPalmiO89051.

Expressioni

Gene expression databases

BgeeiENSMUSG00000022108.
CleanExiMM_ITM2B.
GenevisibleiO89051. MM.

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 (By similarity).By similarity

Protein-protein interaction databases

BioGridi200844. 3 interactors.
IntActiO89051. 2 interactors.
MINTiMINT-1870104.
STRINGi10090.ENSMUSP00000022704.

Structurei

3D structure databases

ProteinModelPortaliO89051.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini137 – 231BRICHOSPROSITE-ProRule annotationAdd BLAST95

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni102 – 134Necessary for interaction with APP and inhibitor effects on APP processingBy similarityAdd BLAST33

Sequence similaritiesi

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

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4681. Eukaryota.
ENOG410XRNN. LUCA.
GeneTreeiENSGT00390000005162.
HOGENOMiHOG000231259.
HOVERGENiHBG059373.
InParanoidiO89051.
KOiK18264.
OMAiKYFAFQQ.
OrthoDBiEOG091G0E78.
PhylomeDBiO89051.
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]

Sequencei

Sequence statusi: Complete.

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

O89051-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVKVTFNSAL AQKEAKKDEP KSSEEALIVP PDAVAVDCKD PGDVVPVGQR
60 70 80 90 100
RAWCWCMCFG LAFMLAGVIL GGAYLYKYFA LQPDDVYYCG LKYIKDDVIL
110 120 130 140 150
NEPSADAPAA RYQTIEENIK IFEEDAVEFI SVPVPEFADS DPANIVHDFN
160 170 180 190 200
KKLTAYLDLN LDKCYVIPLN TSIVMPPKNL LELLINIKAG TYLPQSYLIH
210 220 230 240 250
EHMVITDRIE NVDNLGFFIY RLCHDKETYK LQRRETIRGI QKREASNCFT
260
IRHFENKFAV ETLICS
Length:266
Mass (Da):30,260
Last modified:November 1, 1998 - v1
Checksum:iF3EA640D6E600382
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U76253 mRNA. Translation: AAC63851.1.
AB030203 mRNA. Translation: BAA92766.1.
AK002599 mRNA. Translation: BAB22220.1.
AK003587 mRNA. Translation: BAB22877.1.
AK005125 mRNA. Translation: BAB23828.1.
AK076139 mRNA. Translation: BAC36212.1.
AK077482 mRNA. Translation: BAC36822.1.
AK150378 mRNA. Translation: BAE29510.1.
AK151714 mRNA. Translation: BAE30633.1.
AK151889 mRNA. Translation: BAE30773.1.
AK152068 mRNA. Translation: BAE30922.1.
AK152516 mRNA. Translation: BAE31278.1.
AK152650 mRNA. Translation: BAE31387.1.
AK152731 mRNA. Translation: BAE31452.1.
AK152983 mRNA. Translation: BAE31632.1.
AK153103 mRNA. Translation: BAE31723.1.
AK159340 mRNA. Translation: BAE35002.1.
AK159426 mRNA. Translation: BAE35073.1.
AK159619 mRNA. Translation: BAE35235.1.
AK159628 mRNA. Translation: BAE35242.1.
AK159792 mRNA. Translation: BAE35374.1.
AK159962 mRNA. Translation: BAE35517.1.
AK160725 mRNA. Translation: BAE35970.1.
BC004731 mRNA. Translation: AAH04731.1.
BC010320 mRNA. Translation: AAH10320.1.
BC021786 mRNA. Translation: AAH21786.1.
CCDSiCCDS27269.1.
RefSeqiNP_032436.1. NM_008410.2.
UniGeneiMm.392973.
Mm.4266.

Genome annotation databases

EnsembliENSMUST00000022704; ENSMUSP00000022704; ENSMUSG00000022108.
GeneIDi16432.
KEGGimmu:16432.
UCSCiuc007ups.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U76253 mRNA. Translation: AAC63851.1.
AB030203 mRNA. Translation: BAA92766.1.
AK002599 mRNA. Translation: BAB22220.1.
AK003587 mRNA. Translation: BAB22877.1.
AK005125 mRNA. Translation: BAB23828.1.
AK076139 mRNA. Translation: BAC36212.1.
AK077482 mRNA. Translation: BAC36822.1.
AK150378 mRNA. Translation: BAE29510.1.
AK151714 mRNA. Translation: BAE30633.1.
AK151889 mRNA. Translation: BAE30773.1.
AK152068 mRNA. Translation: BAE30922.1.
AK152516 mRNA. Translation: BAE31278.1.
AK152650 mRNA. Translation: BAE31387.1.
AK152731 mRNA. Translation: BAE31452.1.
AK152983 mRNA. Translation: BAE31632.1.
AK153103 mRNA. Translation: BAE31723.1.
AK159340 mRNA. Translation: BAE35002.1.
AK159426 mRNA. Translation: BAE35073.1.
AK159619 mRNA. Translation: BAE35235.1.
AK159628 mRNA. Translation: BAE35242.1.
AK159792 mRNA. Translation: BAE35374.1.
AK159962 mRNA. Translation: BAE35517.1.
AK160725 mRNA. Translation: BAE35970.1.
BC004731 mRNA. Translation: AAH04731.1.
BC010320 mRNA. Translation: AAH10320.1.
BC021786 mRNA. Translation: AAH21786.1.
CCDSiCCDS27269.1.
RefSeqiNP_032436.1. NM_008410.2.
UniGeneiMm.392973.
Mm.4266.

3D structure databases

ProteinModelPortaliO89051.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200844. 3 interactors.
IntActiO89051. 2 interactors.
MINTiMINT-1870104.
STRINGi10090.ENSMUSP00000022704.

PTM databases

iPTMnetiO89051.
PhosphoSitePlusiO89051.
SwissPalmiO89051.

Proteomic databases

EPDiO89051.
MaxQBiO89051.
PaxDbiO89051.
PeptideAtlasiO89051.
PRIDEiO89051.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022704; ENSMUSP00000022704; ENSMUSG00000022108.
GeneIDi16432.
KEGGimmu:16432.
UCSCiuc007ups.1. mouse.

Organism-specific databases

CTDi9445.
MGIiMGI:1309517. Itm2b.

Phylogenomic databases

eggNOGiKOG4681. Eukaryota.
ENOG410XRNN. LUCA.
GeneTreeiENSGT00390000005162.
HOGENOMiHOG000231259.
HOVERGENiHBG059373.
InParanoidiO89051.
KOiK18264.
OMAiKYFAFQQ.
OrthoDBiEOG091G0E78.
PhylomeDBiO89051.
TreeFamiTF317770.

Miscellaneous databases

ChiTaRSiItm2b. mouse.
PROiO89051.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022108.
CleanExiMM_ITM2B.
GenevisibleiO89051. MM.

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...

Entry informationi

Entry nameiITM2B_MOUSE
AccessioniPrimary (citable) accession number: O89051
Secondary accession number(s): Q545S7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1998
Last modified: November 2, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.