UniProtKB - Q9Y287 (ITM2B_HUMAN)
Integral membrane protein 2B
ITM2B
Functioni
GO - Molecular functioni
- amyloid-beta binding Source: BHF-UCL
- ATP binding Source: Ensembl
GO - Biological processi
- cellular protein metabolic process Source: Reactome
- negative regulation of amyloid precursor protein biosynthetic process Source: UniProtKB
- nervous system development Source: ProtInc
Enzyme and pathway databases
PathwayCommonsi | Q9Y287 |
Reactomei | R-HSA-977225, Amyloid fiber formation |
Protein family/group databases
TCDBi | 1.C.81.1.9, the arenicin (arenicin) family |
Names & Taxonomyi
Protein namesi | Recommended name: Integral membrane protein 2BAlternative 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 Alternative name(s): ABri23 C-terminal peptide P23 peptide |
Gene namesi | Name:ITM2B Synonyms:BRI, BRI2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6174, ITM2B |
MIMi | 603904, gene |
neXtProti | NX_Q9Y287 |
VEuPathDBi | HostDB:ENSG00000136156.12 |
Subcellular locationi
Golgi apparatus
- Golgi apparatus membrane 2 Publications; Single-pass type II membrane protein 1 Publication
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.
Endosome
- Endosome membrane 1 Publication; Single-pass type II membrane protein 1 Publication
Plasma membrane
- Cell membrane 3 Publications; Single-pass type II membrane protein 1 Publication
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.1 Publication
Extracellular region or secreted
- Secreted 3 Publications
Note: Detected in the cerebral spinal fluid (CSF).1 Publication
Extracellular region or secreted
- Secreted 1 Publication
Endosome
- endosome membrane Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: HPA
- Golgi membrane Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- Golgi-associated vesicle membrane Source: UniProtKB
- integral component of organelle membrane Source: UniProtKB
- intracellular membrane-bounded organelle Source: HPA
- membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 54 | CytoplasmicSequence analysisAdd BLAST | 54 | |
Transmembranei | 55 – 75 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 76 – 266 | LumenalSequence analysisAdd BLAST | 191 |
Keywords - Cellular componenti
Amyloid, Cell membrane, Endosome, Golgi apparatus, Membrane, SecretedPathology & Biotechi
Involvement in diseasei
Cerebral amyloid angiopathy, ITM2B-related 1 (CAA-ITM2B1)3 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_010239 | 266 | S → SRTVKKNIIEEN in CAA-ITM2B1; amyloid ABri. 3 Publications | 1 |
Cerebral amyloid angiopathy, ITM2B-related 2 (CAA-ITM2B2)3 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_010240 | 266 | S → FNLFLNSQEKHY in CAA-ITM2B2; amyloid ADan; colocalizes with APP amyloid-beta protein 42 in parenchymal and vascular lesions; interacts with APP amyloid-beta protein 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 | 1 |
Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities (RDGCA)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_072434 | 261 | E → A in RDGCA. 1 PublicationCorresponds to variant dbSNP:rs606231283EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 60 | G → V: Reduces strongly intramembrane cleavage by SPPL2B. 1 Publication | 1 | |
Mutagenesisi | 170 | N → A: Accumulates in intracellular compartments. Does not inhibit furin, ADAM10 and SPPL2A extracellular proteolytic processing activity. 1 Publication | 1 | |
Mutagenesisi | 243 – 244 | RE → AA: Inhibits cleavage by furin. Does not prevent ADAM10 shedding. 2 Publications | 2 |
Keywords - Diseasei
Amyloidosis, Deafness, Disease variant, NeurodegenerationOrganism-specific databases
DisGeNETi | 9445 |
MalaCardsi | ITM2B |
MIMi | 117300, phenotype 176500, phenotype 616079, phenotype |
OpenTargetsi | ENSG00000136156 |
Orphaneti | 97345, ABri amyloidosis 97346, ADan amyloidosis 397758, Retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies |
PharmGKBi | PA29971 |
Miscellaneous databases
Pharosi | Q9Y287, Tbio |
Genetic variation databases
BioMutai | ITM2B |
DMDMi | 12643343 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000045840 | 1 – 266 | Integral membrane protein 2BAdd BLAST | 266 | |
ChainiPRO_0000417464 | 1 – 243 | BRI2, membrane formAdd BLAST | 243 | |
ChainiPRO_0000417465 | 1 – ? | BRI2 intracellular domain | ||
ChainiPRO_0000417466 | ? – 243 | BRI2C, soluble form | ||
PeptideiPRO_0000016545 | 244 – 266 | Bri23 peptideAdd BLAST | 23 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 89 | Interchain | ||
Disulfide bondi | 164 ↔ 223 | By similarity | ||
Glycosylationi | 170 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 248 ↔ 265 | Interchain (between ADan peptide variants) |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 243 – 244 | Cleavage; by furin | 2 |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, GlycoproteinProteomic databases
EPDi | Q9Y287 |
jPOSTi | Q9Y287 |
MassIVEi | Q9Y287 |
PaxDbi | Q9Y287 |
PeptideAtlasi | Q9Y287 |
PRIDEi | Q9Y287 |
ProteomicsDBi | 85699 [Q9Y287-1] |
TopDownProteomicsi | Q9Y287-1 [Q9Y287-1] |
PTM databases
GlyConnecti | 1403, 2 N-Linked glycans (1 site) |
GlyGeni | Q9Y287, 1 site |
iPTMneti | Q9Y287 |
PhosphoSitePlusi | Q9Y287 |
SwissPalmi | Q9Y287 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000136156, Expressed in metanephric glomerulus and 247 other tissues |
ExpressionAtlasi | Q9Y287, baseline and differential |
Genevisiblei | Q9Y287, HS |
Organism-specific databases
HPAi | ENSG00000136156, Tissue enhanced (epididymis) |
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 amyloid-beta protein 40.
7 PublicationsBinary interactionsi
Hide detailsQ9Y287
Protein-protein interaction databases
BioGRIDi | 114835, 49 interactors |
IntActi | Q9Y287, 44 interactors |
MINTi | Q9Y287 |
STRINGi | 9606.ENSP00000367828 |
Miscellaneous databases
RNActi | Q9Y287, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 137 – 231 | BRICHOSPROSITE-ProRule annotationAdd BLAST | 95 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 102 – 134 | Necessary for interaction with APP and inhibitor effects on APP processingAdd BLAST | 33 |
Sequence similaritiesi
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4681, Eukaryota |
GeneTreei | ENSGT00950000183115 |
HOGENOMi | CLU_074596_0_0_1 |
InParanoidi | Q9Y287 |
OMAi | KYFAFQQ |
OrthoDBi | 1322680at2759 |
PhylomeDBi | Q9Y287 |
TreeFami | TF317770 |
Family and domain databases
InterProi | View protein in InterPro IPR007084, BRICHOS_dom IPR040145, ITM2 |
PANTHERi | PTHR10962, PTHR10962, 1 hit |
Pfami | View protein in Pfam PF04089, BRICHOS, 1 hit |
SMARTi | View protein in SMART SM01039, BRICHOS, 1 hit |
PROSITEi | View protein in PROSITE PS50869, BRICHOS, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A3B3ITP9 | A0A3B3ITP9_HUMAN | Integral membrane protein 2 | ITM2B | 143 | Annotation score: | ||
A0A3B3IUC0 | A0A3B3IUC0_HUMAN | Integral membrane protein 2 | ITM2B | 210 | Annotation score: | ||
A0A3B3ISG3 | A0A3B3ISG3_HUMAN | Integral membrane protein 2 | ITM2B | 67 | Annotation score: | ||
A0A3B3IU60 | A0A3B3IU60_HUMAN | Integral membrane protein 2B | ITM2B | 45 | Annotation score: | ||
U3KQL7 | U3KQL7_HUMAN | Integral membrane protein 2B | ITM2B | 28 | Annotation score: | ||
U3KQ52 | U3KQ52_HUMAN | Integral membrane protein 2B | ITM2B | 53 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_071047 | 15 | A → T2 PublicationsCorresponds to variant dbSNP:rs11556905Ensembl. | 1 | |
Natural variantiVAR_072434 | 261 | E → A in RDGCA. 1 PublicationCorresponds to variant dbSNP:rs606231283EnsemblClinVar. | 1 | |
Natural variantiVAR_010240 | 266 | S → FNLFLNSQEKHY in CAA-ITM2B2; amyloid ADan; colocalizes with APP amyloid-beta protein 42 in parenchymal and vascular lesions; interacts with APP amyloid-beta protein 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 | 1 | |
Natural variantiVAR_010239 | 266 | S → SRTVKKNIIEEN in CAA-ITM2B1; amyloid ABri. 3 Publications | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_055326 | 83 – 188 | Missing in isoform 2. CuratedAdd BLAST | 106 |
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 |
CCDSi | CCDS9409.1 [Q9Y287-1] |
RefSeqi | NP_068839.1, NM_021999.4 [Q9Y287-1] |
Genome annotation databases
Ensembli | ENST00000378549; ENSP00000367811; ENSG00000136156 [Q9Y287-2] ENST00000647800; ENSP00000497221; ENSG00000136156 [Q9Y287-1] |
GeneIDi | 9445 |
KEGGi | hsa:9445 |
UCSCi | uc001vbz.4, human [Q9Y287-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS9409.1 [Q9Y287-1] |
RefSeqi | NP_068839.1, NM_021999.4 [Q9Y287-1] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 114835, 49 interactors |
IntActi | Q9Y287, 44 interactors |
MINTi | Q9Y287 |
STRINGi | 9606.ENSP00000367828 |
Protein family/group databases
TCDBi | 1.C.81.1.9, the arenicin (arenicin) family |
PTM databases
GlyConnecti | 1403, 2 N-Linked glycans (1 site) |
GlyGeni | Q9Y287, 1 site |
iPTMneti | Q9Y287 |
PhosphoSitePlusi | Q9Y287 |
SwissPalmi | Q9Y287 |
Genetic variation databases
BioMutai | ITM2B |
DMDMi | 12643343 |
Proteomic databases
EPDi | Q9Y287 |
jPOSTi | Q9Y287 |
MassIVEi | Q9Y287 |
PaxDbi | Q9Y287 |
PeptideAtlasi | Q9Y287 |
PRIDEi | Q9Y287 |
ProteomicsDBi | 85699 [Q9Y287-1] |
TopDownProteomicsi | Q9Y287-1 [Q9Y287-1] |
Protocols and materials databases
Antibodypediai | 23811, 250 antibodies |
DNASUi | 9445 |
Genome annotation databases
Ensembli | ENST00000378549; ENSP00000367811; ENSG00000136156 [Q9Y287-2] ENST00000647800; ENSP00000497221; ENSG00000136156 [Q9Y287-1] |
GeneIDi | 9445 |
KEGGi | hsa:9445 |
UCSCi | uc001vbz.4, human [Q9Y287-1] |
Organism-specific databases
CTDi | 9445 |
DisGeNETi | 9445 |
GeneCardsi | ITM2B |
HGNCi | HGNC:6174, ITM2B |
HPAi | ENSG00000136156, Tissue enhanced (epididymis) |
MalaCardsi | ITM2B |
MIMi | 117300, phenotype 176500, phenotype 603904, gene 616079, phenotype |
neXtProti | NX_Q9Y287 |
OpenTargetsi | ENSG00000136156 |
Orphaneti | 97345, ABri amyloidosis 97346, ADan amyloidosis 397758, Retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies |
PharmGKBi | PA29971 |
VEuPathDBi | HostDB:ENSG00000136156.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4681, Eukaryota |
GeneTreei | ENSGT00950000183115 |
HOGENOMi | CLU_074596_0_0_1 |
InParanoidi | Q9Y287 |
OMAi | KYFAFQQ |
OrthoDBi | 1322680at2759 |
PhylomeDBi | Q9Y287 |
TreeFami | TF317770 |
Enzyme and pathway databases
PathwayCommonsi | Q9Y287 |
Reactomei | R-HSA-977225, Amyloid fiber formation |
Miscellaneous databases
BioGRID-ORCSi | 9445, 36 hits in 881 CRISPR screens |
ChiTaRSi | ITM2B, human |
GeneWikii | ITM2B |
GenomeRNAii | 9445 |
Pharosi | Q9Y287, Tbio |
PROi | PR:Q9Y287 |
RNActi | Q9Y287, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000136156, Expressed in metanephric glomerulus and 247 other tissues |
ExpressionAtlasi | Q9Y287, baseline and differential |
Genevisiblei | Q9Y287, HS |
Family and domain databases
InterProi | View protein in InterPro IPR007084, BRICHOS_dom IPR040145, ITM2 |
PANTHERi | PTHR10962, PTHR10962, 1 hit |
Pfami | View protein in Pfam PF04089, BRICHOS, 1 hit |
SMARTi | View protein in SMART SM01039, BRICHOS, 1 hit |
PROSITEi | View protein in PROSITE PS50869, BRICHOS, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ITM2B_HUMAN | |
Accessioni | Q9Y287Primary (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: | February 10, 2021 | |
This is version 178 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 13
Human chromosome 13: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families