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Q5XIE8

- ITM2B_RAT

UniProt

Q5XIE8 - ITM2B_RAT

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Protein

Integral membrane protein 2B

Gene

Itm2b

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript 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

Sites

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

GO - Molecular functioni

  1. ATP binding Source: Ensembl
  2. beta-amyloid binding Source: Ensembl

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
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_199225. Amyloids.

Names & Taxonomyi

Protein namesi
Recommended 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:
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 15

Organism-specific databases

RGDi620727. Itm2b.

Subcellular locationi

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

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

  1. endosome Source: UniProtKB-KW
  2. extracellular space Source: UniProtKB
  3. extracellular vesicular exosome Source: Ensembl
  4. Golgi-associated vesicle membrane Source: UniProtKB
  5. integral component of organelle membrane Source: UniProtKB
  6. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Golgi apparatus, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 243BRI2C, soluble formBy similarityPRO_0000417489
Chaini1 – 266266Integral membrane protein 2BPRO_0000154824Add
BLAST
Chaini1 – 243243BRI2, membrane formBy similarityPRO_0000417487Add
BLAST
Chaini1 – ?BRI2 intracellular domainBy similarityPRO_0000417488
Peptidei244 – 26623Bri23 peptideBy similarityPRO_0000417490Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi89 – 89InterchainBy similarity
Disulfide bondi164 ↔ 223By similarity
Glycosylationi170 – 1701N-linked (GlcNAc...)Sequence Analysis
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

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ5XIE8.
PRIDEiQ5XIE8.

PTM databases

PhosphoSiteiQ5XIE8.

Expressioni

Gene expression databases

GenevestigatoriQ5XIE8.

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

BioGridi253181. 1 interaction.
MINTiMINT-4580553.
STRINGi10116.ENSRNOP00000023037.

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 processingBy similarityAdd
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.
InParanoidiQ5XIE8.
KOiK18264.
OMAiVTIRHFE.
OrthoDBiEOG70KGQD.
PhylomeDBiQ5XIE8.
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.

Q5XIE8-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVKVTFNSAL AQKEAKKDEP KSSEEALIAP PDAVAVDCKD PDDVVPVGQR
60 70 80 90 100
RAWCWCMCFG LAFMLAGVIL GGAYLYKYFA LQPDDVYYCG LKYIKDDVIL
110 120 130 140 150
SEPSADAPAA RYQTIEENIK IFEEDAVEFI SVPVPEFADS DPANIVHDFN
160 170 180 190 200
KKLTAYLDLN LDKCYVIPLN TSIVMPPRNL LELLINIKAG TYLPQSYLIH
210 220 230 240 250
EHMVITDRIE NVDHLGFFIY RLCHDKETYK LQRRETIRGI QKREASNCFT
260
IRHFENKFAV ETLICS
Length:266
Mass (Da):30,314
Last modified:November 23, 2004 - v1
Checksum:iE3925091C653C449
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC083735 mRNA. Translation: AAH83735.1.
RefSeqiNP_001006964.1. NM_001006963.1.
UniGeneiRn.107335.

Genome annotation databases

EnsembliENSRNOT00000023037; ENSRNOP00000023037; ENSRNOG00000016271.
GeneIDi290364.
KEGGirno:290364.
UCSCiRGD:620727. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC083735 mRNA. Translation: AAH83735.1 .
RefSeqi NP_001006964.1. NM_001006963.1.
UniGenei Rn.107335.

3D structure databases

ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 253181. 1 interaction.
MINTi MINT-4580553.
STRINGi 10116.ENSRNOP00000023037.

PTM databases

PhosphoSitei Q5XIE8.

Proteomic databases

PaxDbi Q5XIE8.
PRIDEi Q5XIE8.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000023037 ; ENSRNOP00000023037 ; ENSRNOG00000016271 .
GeneIDi 290364.
KEGGi rno:290364.
UCSCi RGD:620727. rat.

Organism-specific databases

CTDi 9445.
RGDi 620727. Itm2b.

Phylogenomic databases

eggNOGi NOG283703.
GeneTreei ENSGT00390000005162.
HOGENOMi HOG000231259.
HOVERGENi HBG059373.
InParanoidi Q5XIE8.
KOi K18264.
OMAi VTIRHFE.
OrthoDBi EOG70KGQD.
PhylomeDBi Q5XIE8.
TreeFami TF317770.

Enzyme and pathway databases

Reactomei REACT_199225. Amyloids.

Miscellaneous databases

NextBioi 630989.
PROi Q5XIE8.

Gene expression databases

Genevestigatori Q5XIE8.

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

  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.

Entry informationi

Entry nameiITM2B_RAT
AccessioniPrimary (citable) accession number: Q5XIE8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2006
Last sequence update: November 23, 2004
Last modified: October 29, 2014
This is version 72 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3