ID ITM2B_HUMAN Reviewed; 266 AA. AC Q9Y287; Q5W0A3; Q96B24; Q9NYH1; DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 27-MAR-2024, entry version 193. DE RecName: Full=Integral membrane protein 2B; DE AltName: Full=Immature BRI2; DE Short=imBRI2; DE AltName: Full=Protein E25B; DE AltName: Full=Transmembrane protein BRI; DE Short=Bri; DE Contains: DE RecName: Full=BRI2, membrane form; DE AltName: Full=Mature BRI2; DE Short=mBRI2; DE Contains: DE RecName: Full=BRI2 intracellular domain; DE Short=BRI2 ICD; DE Contains: DE RecName: Full=BRI2C, soluble form; DE Contains: DE RecName: Full=Bri23 peptide; DE Short=Bri2-23; DE AltName: Full=ABri23; DE AltName: Full=C-terminal peptide; DE AltName: Full=P23 peptide; GN Name=ITM2B; Synonyms=BRI, BRI2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN CAA-ITM2B1, AND VARIANT RP CAA-ITM2B1 ARG-THR-VAL-LYS-LYS-ASN-ILE-ILE-GLU-GLU-ASN-266 INS. RC TISSUE=Pituitary; RX PubMed=10391242; DOI=10.1038/21637; RA Vidal R., Frangione B., Rostagno A., Mead S., Revesz T., Plant G., RA Ghiso J.; RT "A stop-codon mutation in the BRI gene associated with familial British RT dementia."; RL Nature 399:776-781(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN CAA-ITM2B2, AND VARIANT RP CAA-ITM2B2 SER-266 DELINS PHE-ASN-LEU-PHE-LEU-ASN-SER-GLN-GLU-LYS-HIS-TYR. RX PubMed=10781099; DOI=10.1073/pnas.080076097; RA Vidal R., Revesz T., Rostagno A., Kim E., Holton J.L., Bek T., RA Bojsen-Moeller M., Braendgaard H., Plant G., Ghiso J., Frangione B.; RT "A decamer duplication in the 3' region of the BRI gene originates an RT amyloid peptide that is associated with dementia in a Danish kindred."; RL Proc. Natl. Acad. Sci. U.S.A. 97:4920-4925(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Adrenal gland; RA Ren S., Shi J., Huang C., Jiang C., Li Y., Zhou J., Yu Y., Xu S., Wang Y., RA Fu G., Chen Z., Han Z.; RT "A novel gene expressed in human adrenal gland."; RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pituitary; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-15. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-15. RC TISSUE=Brain, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP INVOLVEMENT IN RDGCA, AND VARIANT RDGCA ALA-261. RX PubMed=24026677; DOI=10.1093/hmg/ddt439; RA Audo I., Bujakowska K., Orhan E., El Shamieh S., Sennlaub F., RA Guillonneau X., Antonio A., Michiels C., Lancelot M.E., Letexier M., RA Saraiva J.P., Nguyen H., Luu T.D., Leveillard T., Poch O., Dollfus H., RA Paques M., Goureau O., Mohand-Said S., Bhattacharya S.S., Sahel J.A., RA Zeitz C.; RT "The familial dementia gene revisited: a missense mutation revealed by RT whole-exome sequencing identifies ITM2B as a candidate gene underlying a RT novel autosomal dominant retinal dystrophy in a large family."; RL Hum. Mol. Genet. 23:491-501(2014). RN [10] RP CHARACTERIZATION OF VARIANT CAA-ITM2B1 RP ARG-THR-VAL-LYS-LYS-ASN-ILE-ILE-GLU-GLU-ASN-266 INS, TOPOLOGY, CLEAVAGE BY RP FURIN, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=10526337; DOI=10.1038/14783; RA Kim S.H., Wang R., Gordon D.J., Bass J., Steiner D.F., Lynn D.G., RA Thinakaran G., Meredith S.C., Sisodia S.S.; RT "Furin mediates enhanced production of fibrillogenic ABri peptides in RT familial British dementia."; RL Nat. Neurosci. 2:984-988(1999). RN [11] RP FUNCTION, TOPOLOGY, PROTEOLYTIC CLEAVAGE, CHARACTERIZATION OF VARIANT RP CAA-ITM2B1 ARG-THR-VAL-LYS-LYS-ASN-ILE-ILE-GLU-GLU-ASN-266 INS, RP CHARACTERIZATION OF VARIANT CAA-ITM2B2 SER-266 DELINS RP PHE-ASN-LEU-PHE-LEU-ASN-SER-GLN-GLU-LYS-HIS-TYR, AND SUBCELLULAR LOCATION. RX PubMed=14656991; DOI=10.1096/fj.03-0730fje; RA Choi S.I., Vidal R., Frangione B., Levy E.; RT "Axonal transport of British and Danish amyloid peptides via secretory RT vesicles."; RL FASEB J. 18:373-375(2004). RN [12] RP FUNCTION, AND INTERACTION WITH APP. RX PubMed=15983050; DOI=10.1074/jbc.c500217200; RA Matsuda S., Giliberto L., Matsuda Y., Davies P., McGowan E., Pickford F., RA Ghiso J., Frangione B., D'Adamio L.; RT "The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta RT precursor protein and inhibits amyloid-beta production."; RL J. Biol. Chem. 280:28912-28916(2005). RN [13] RP FUNCTION, AND INTERACTION WITH APP. RX PubMed=16027166; DOI=10.1074/jbc.c500231200; RA Fotinopoulou A., Tsachaki M., Vlavaki M., Poulopoulos A., Rostagno A., RA Frangione B., Ghiso J., Efthimiopoulos S.; RT "BRI2 interacts with amyloid precursor protein (APP) and regulates amyloid RT beta (Abeta) production."; RL J. Biol. Chem. 280:30768-30772(2005). RN [14] RP CHARACTERIZATION OF VARIANT CAA-ITM2B2 SER-266 DELINS RP PHE-ASN-LEU-PHE-LEU-ASN-SER-GLN-GLU-LYS-HIS-TYR. RX PubMed=16091362; DOI=10.1074/jbc.m504038200; RA Tomidokoro Y., Lashley T., Rostagno A., Neubert T.A., Bojsen-Moller M., RA Braendgaard H., Plant G., Holton J., Frangione B., Revesz T., Ghiso J.; RT "Familial Danish dementia: co-existence of Danish and Alzheimer amyloid RT subunits (ADan AND A{beta}) in the absence of compact plaques."; RL J. Biol. Chem. 280:36883-36894(2005). RN [15] RP SUBCELLULAR LOCATION, TOPOLOGY, CLEAVAGE BY ADAM10; FURIN; SPPL2A AND RP SPPL2B, INTERACTION WITH SPPL2A AND SPPL2B, AND MUTAGENESIS OF RP 243-ARG-GLU-244. RX PubMed=17965014; DOI=10.1074/jbc.m706661200; RA Martin L., Fluhrer R., Reiss K., Kremmer E., Saftig P., Haass C.; RT "Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and RT SPPL2a/SPPL2b."; RL J. Biol. Chem. 283:1644-1652(2008). RN [16] RP FUNCTION OF SECRETED BRI23 PEPTIDE, SUBCELLULAR LOCATION, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=18524908; DOI=10.1523/jneurosci.0891-08.2008; RA Kim J., Miller V.M., Levites Y., West K.J., Zwizinski C.W., Moore B.D., RA Troendle F.J., Bann M., Verbeeck C., Price R.W., Smithson L., Sonoda L., RA Wagg K., Rangachari V., Zou F., Younkin S.G., Graff-Radford N., Dickson D., RA Rosenberry T., Golde T.E.; RT "BRI2 (ITM2b) inhibits Abeta deposition in vivo."; RL J. Neurosci. 28:6030-6036(2008). RN [17] RP FUNCTION. RX PubMed=18753367; DOI=10.1523/jneurosci.2094-08.2008; RA Matsuda S., Giliberto L., Matsuda Y., McGowan E.M., D'Adamio L.; RT "BRI2 inhibits amyloid beta-peptide precursor protein processing by RT interfering with the docking of secretases to the substrate."; RL J. Neurosci. 28:8668-8676(2008). RN [18] RP CLEAVAGE BY ADAM10; FURIN AND SPPL2B, AND SUBCELLULAR LOCATION. RX PubMed=19114711; DOI=10.1074/jbc.m807485200; RA Martin L., Fluhrer R., Haass C.; RT "Substrate requirements for SPPL2b-dependent regulated intramembrane RT proteolysis."; RL J. Biol. Chem. 284:5662-5670(2009). RN [19] RP FUNCTION OF SECRETED BRI23 PEPTIDE, SUBUNIT, INTERACTION WITH APP RP AMYLOID-BETA PROTEIN 40, DISULFIDE BOND, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=20036644; DOI=10.1016/j.bbrc.2009.12.122; RA Peng S., Fitzen M., Jornvall H., Johansson J.; RT "The extracellular domain of Bri2 (ITM2B) binds the ABri peptide (1-23) and RT amyloid beta-peptide (Abeta1-40): Implications for Bri2 effects on RT processing of amyloid precursor protein and Abeta aggregation."; RL Biochem. Biophys. Res. Commun. 393:356-361(2010). RN [20] RP SUBCELLULAR LOCATION, SUBUNIT, AND DISULFIDE BONDS. RX PubMed=18440095; DOI=10.1016/j.neurobiolaging.2008.03.004; RA Tsachaki M., Ghiso J., Rostagno A., Efthimiopoulos S.; RT "BRI2 homodimerizes with the involvement of intermolecular disulfide RT bonds."; RL Neurobiol. Aging 31:88-98(2010). RN [21] RP CLEAVAGE BY ADAM10; FURIN AND SPPL2B, GLYCOSYLATION AT ASN-170, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF ASN-170. RX PubMed=21752865; DOI=10.1093/glycob/cwr097; RA Tsachaki M., Serlidaki D., Fetani A., Zarkou V., Rozani I., Ghiso J., RA Efthimiopoulos S.; RT "Glycosylation of BRI2 on asparagine 170 is involved in its trafficking to RT the cell surface but not in its processing by furin or ADAM10."; RL Glycobiology 21:1382-1388(2011). RN [22] RP FUNCTION OF MBRI2 IN APP PROCESSING INHIBITION, INTERACTION WITH APP RP AMYLOID-BETA A4 AND APP C99, PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, RP AND MUTAGENESIS OF 243-ARG-GLU-244. RX PubMed=19748705; DOI=10.1016/j.neurobiolaging.2009.08.005; RA Matsuda S., Matsuda Y., Snapp E.L., D'Adamio L.; RT "Maturation of BRI2 generates a specific inhibitor that reduces APP RT processing at the plasma membrane and in endocytic vesicles."; RL Neurobiol. Aging 32:1400-1408(2011). RN [23] RP FUNCTION OF MBRI2 IN APP PROCESSING INHIBITION, AND INTERACTION WITH APP RP AMYLOID-BETA A4 AND APP C99. RX PubMed=22170863; DOI=10.1002/emmm.201100195; RA Tamayev R., Matsuda S., Arancio O., D'Adamio L.; RT "beta- but not gamma-secretase proteolysis of APP causes synaptic and RT memory deficits in a mouse model of dementia."; RL EMBO Mol. Med. 4:171-179(2012). RN [24] RP CLEAVAGE BY SPPL2A AND SPPL2B, AND MUTAGENESIS OF GLY-60. RX PubMed=22194595; DOI=10.1074/jbc.m111.328104; RA Fluhrer R., Martin L., Klier B., Haug-Kroper M., Grammer G., Nuscher B., RA Haass C.; RT "The alpha-helical content of the transmembrane domain of the British RT dementia protein-2 (Bri2) determines its processing by signal peptide RT peptidase-like 2b (SPPL2b)."; RL J. Biol. Chem. 287:5156-5163(2012). CC -!- FUNCTION: Plays a regulatory role in the processing of the amyloid-beta CC A4 precursor protein (APP) and acts as an inhibitor of the amyloid-beta CC peptide aggregation and fibrils deposition. Plays a role in the CC induction of neurite outgrowth. Functions as a protease inhibitor by CC blocking access of secretases to APP cleavage sites. CC -!- FUNCTION: Mature BRI2 (mBRI2) functions as a modulator of the amyloid- CC beta A4 precursor protein (APP) processing leading to a strong CC reduction in the secretion of secretase-processed amyloid-beta protein CC 40 and amyloid-beta protein 42. CC -!- FUNCTION: Bri23 peptide prevents aggregation of APP amyloid-beta CC protein 42 into toxic oligomers. CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with SPPL2A and SPPL2B. CC Interacts with APP. Mature BRI2 (mBRI2) interacts with the APP amyloid- CC beta A4 protein; the interaction occurs at the cell surface and in the CC endocytic compartments and enable alpha- and beta-secretase-induced APP CC cleavage inhibition. Mature BRI2 (mBRI2) interacts with the APP C99; CC the interaction occurs in the endocytic compartments and enable gamma- CC secretase-induced C99 cleavage inhibition. May form heterodimers with CC Bri23 peptide and APP amyloid-beta protein 40. Interacts with ADAM7 in CC sperm; the interaction increases following capacitation (By CC similarity). {ECO:0000250|UniProtKB:O89051, CC ECO:0000269|PubMed:15983050, ECO:0000269|PubMed:16027166, CC ECO:0000269|PubMed:17965014, ECO:0000269|PubMed:18440095, CC ECO:0000269|PubMed:19748705, ECO:0000269|PubMed:20036644, CC ECO:0000269|PubMed:22170863}. CC -!- INTERACTION: CC Q9Y287; P05067: APP; NbExp=4; IntAct=EBI-2866431, EBI-77613; CC Q9Y287; P05067-8: APP; NbExp=4; IntAct=EBI-2866431, EBI-302661; CC Q9Y287; P56817: BACE1; NbExp=4; IntAct=EBI-2866431, EBI-2433139; CC Q9Y287; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-2866431, EBI-749265; CC Q9Y287; P26715: KLRC1; NbExp=3; IntAct=EBI-2866431, EBI-9018187; CC Q9Y287; Q58DX5: NAALADL2; NbExp=3; IntAct=EBI-2866431, EBI-10178964; CC Q9Y287; Q96E17: RAB3C; NbExp=3; IntAct=EBI-2866431, EBI-4287022; CC Q9Y287; Q9NRM0-1: SLC2A9; NbExp=4; IntAct=EBI-2866431, EBI-25396304; CC Q9Y287; Q9NRM0-2: SLC2A9; NbExp=2; IntAct=EBI-2866431, EBI-25396386; CC Q9Y287; Q8N205: SYNE4; NbExp=3; IntAct=EBI-2866431, EBI-7131783; CC -!- SUBCELLULAR LOCATION: [Integral membrane protein 2B]: Golgi apparatus CC membrane {ECO:0000269|PubMed:14656991, ECO:0000269|PubMed:19114711}; CC Single-pass type II membrane protein {ECO:0000269|PubMed:10526337}. CC Note=Immature BRI2 (imBRI2) is cleaved by furin in the Golgi into mBRI2 CC and a Bri23 peptide. mBRI2 is transported to the plasma membrane and CC Bri23 peptide is secreted. CC -!- SUBCELLULAR LOCATION: [BRI2, membrane form]: Cell membrane CC {ECO:0000269|PubMed:18440095, ECO:0000269|PubMed:19748705, CC ECO:0000269|PubMed:21752865}; Single-pass type II membrane protein CC {ECO:0000269|PubMed:10526337}. Endosome membrane CC {ECO:0000269|PubMed:19748705}; Single-pass type II membrane protein CC {ECO:0000269|PubMed:10526337}. Note=Mature BRI2 (mBRI2) needs to be CC transported from the endoplasmic reticulum compartment to the cell CC membrane in order to be able to inhibit APP processing. CC {ECO:0000269|PubMed:19748705}. CC -!- SUBCELLULAR LOCATION: [Bri23 peptide]: Secreted CC {ECO:0000269|PubMed:10526337, ECO:0000269|PubMed:14656991, CC ECO:0000269|PubMed:18524908}. Note=Detected in the cerebral spinal CC fluid (CSF). {ECO:0000269|PubMed:18524908}. CC -!- SUBCELLULAR LOCATION: [BRI2C, soluble form]: Secreted CC {ECO:0000269|PubMed:17965014}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y287-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y287-2; Sequence=VSP_055326; CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in brain. CC -!- PTM: The ectodomain C-terminal part of the imBRI2 is processed by furin CC producing a secreted Bri23 peptide and a mature BRI2, membrane form CC (mBRI2). The remaining part of the ectodomain of mBRI2 containing the CC BRICHOS domain is cleaved by ADAM10 and is secreted (BRI2C, soluble CC form). The membrane-bound N-terminal fragment (BRI2C, membrane form) is CC further proteolytically processed by SPPL2A and SPPL2B through CC regulated intramembrane proteolysis producing a secreted C-peptide and CC a BRI2 intracellular domain (BRI2 ICD) released in the cytosol. CC Shedding by ADAM10 facilitates intramembrane cleavage but is not CC absolutely required for BRI2 ICD generation. CC -!- PTM: Glycosylation at Asn-170 is important for cell surface CC localization, but doesn't affect furin- and ADAM10-induced proteolytic CC processing. {ECO:0000269|PubMed:21752865}. CC -!- DISEASE: Cerebral amyloid angiopathy, ITM2B-related 1 (CAA-ITM2B1) CC [MIM:176500]: A disorder characterized by amyloid deposition in the CC walls of cerebral blood vessels and neurodegeneration in the central CC nervous system. Cerebral amyloid angiopathy, non-neuritic and CC perivascular plaques and neurofibrillary tangles are the predominant CC pathological lesions. Clinical features include progressive mental CC deterioration, spasticity and muscular rigidity. CC {ECO:0000269|PubMed:10391242, ECO:0000269|PubMed:10526337, CC ECO:0000269|PubMed:14656991}. Note=The disease is caused by variants CC affecting the gene represented in this entry. A single base CC substitution at the stop codon of ITM2B generates a 277-residue CC precursor that is cleaved at the normal furin processing site to CC generate the ABri amyloidogenic peptide (PubMed:10391242). ABri CC accumulates in the brain and produces amyloid fibrils responsible for CC neuronal dysfunction and dementia. ABri peptide variant forms fibrils CC in vitro (PubMed:10526337). {ECO:0000269|PubMed:10391242, CC ECO:0000269|PubMed:10526337}. CC -!- DISEASE: Cerebral amyloid angiopathy, ITM2B-related 2 (CAA-ITM2B2) CC [MIM:117300]: A disorder characterized by amyloid deposition in the CC walls of the blood vessels of the cerebrum, choroid plexus, cerebellum, CC spinal cord and retina. Plaques and neurofibrillary tangles are CC observed in the hippocampus. Clinical features include progressive CC ataxia, dementia, cataracts and deafness. {ECO:0000269|PubMed:10781099, CC ECO:0000269|PubMed:14656991, ECO:0000269|PubMed:16091362}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. A decamer duplication in the 3' region of ITM2B results in the CC production of the ADan amyloidogenic peptide (PubMed:10781099). ADan is CC generated by cleavage of the mutated precursor at the normal furin CC processing site. ADan accumulates in the brain and produces amyloid CC fibrils responsible for neuronal dysfunction and dementia. CC {ECO:0000269|PubMed:10781099}. CC -!- DISEASE: Retinal dystrophy with inner retinal dysfunction and ganglion CC cell abnormalities (RDGCA) [MIM:616079]: An autosomal dominant retinal CC dystrophy characterized by inner retinal dysfunction in association CC with ganglion cell abnormalities. Clinical features include mild CC photophobia, progressive loss of central vision, night blindness, and CC hyperreflectivity of nerve and ganglion cell layers. CC {ECO:0000269|PubMed:24026677}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ITM2 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/itm2b/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF152462; AAD45280.1; -; mRNA. DR EMBL; AF246221; AAF66130.1; -; mRNA. DR EMBL; AF136973; AAG49434.1; -; mRNA. DR EMBL; AF092128; AAD40370.1; -; mRNA. DR EMBL; BT006863; AAP35509.1; -; mRNA. DR EMBL; AY341247; AAP88930.1; -; Genomic_DNA. DR EMBL; CH471075; EAX08789.1; -; Genomic_DNA. DR EMBL; CH471075; EAX08790.1; -; Genomic_DNA. DR EMBL; BC000554; AAH00554.1; -; mRNA. DR EMBL; BC016148; AAH16148.1; -; mRNA. DR CCDS; CCDS9409.1; -. [Q9Y287-1] DR RefSeq; NP_068839.1; NM_021999.4. [Q9Y287-1] DR AlphaFoldDB; Q9Y287; -. DR EMDB; EMD-3918; -. DR SMR; Q9Y287; -. DR BioGRID; 114835; 137. DR IntAct; Q9Y287; 54. DR MINT; Q9Y287; -. DR STRING; 9606.ENSP00000497221; -. DR TCDB; 1.C.81.2.1; the arenicin (arenicin) family. DR GlyConnect; 1403; 2 N-Linked glycans (1 site). DR GlyCosmos; Q9Y287; 1 site, 2 glycans. DR GlyGen; Q9Y287; 1 site, 2 N-linked glycans (1 site). DR iPTMnet; Q9Y287; -. DR PhosphoSitePlus; Q9Y287; -. DR SwissPalm; Q9Y287; -. DR BioMuta; ITM2B; -. DR DMDM; 12643343; -. DR EPD; Q9Y287; -. DR jPOST; Q9Y287; -. DR MassIVE; Q9Y287; -. DR MaxQB; Q9Y287; -. DR PaxDb; 9606-ENSP00000367828; -. DR PeptideAtlas; Q9Y287; -. DR ProteomicsDB; 85699; -. [Q9Y287-1] DR Pumba; Q9Y287; -. DR TopDownProteomics; Q9Y287-1; -. [Q9Y287-1] DR Antibodypedia; 23811; 285 antibodies from 31 providers. DR DNASU; 9445; -. DR Ensembl; ENST00000378549.5; ENSP00000367811.5; ENSG00000136156.15. [Q9Y287-2] DR Ensembl; ENST00000647800.2; ENSP00000497221.1; ENSG00000136156.15. [Q9Y287-1] DR GeneID; 9445; -. DR KEGG; hsa:9445; -. DR MANE-Select; ENST00000647800.2; ENSP00000497221.1; NM_021999.5; NP_068839.1. DR UCSC; uc001vbz.4; human. [Q9Y287-1] DR AGR; HGNC:6174; -. DR DisGeNET; 9445; -. DR GeneCards; ITM2B; -. DR HGNC; HGNC:6174; ITM2B. DR HPA; ENSG00000136156; Low tissue specificity. DR MalaCards; ITM2B; -. DR MIM; 117300; phenotype. DR MIM; 176500; phenotype. DR MIM; 603904; gene. DR MIM; 616079; phenotype. DR neXtProt; NX_Q9Y287; -. DR OpenTargets; ENSG00000136156; -. DR Orphanet; 97345; ABri amyloidosis. DR Orphanet; 97346; ADan amyloidosis. DR Orphanet; 397758; Retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies. DR PharmGKB; PA29971; -. DR VEuPathDB; HostDB:ENSG00000136156; -. DR eggNOG; KOG4681; Eukaryota. DR GeneTree; ENSGT00950000183115; -. DR HOGENOM; CLU_074596_0_0_1; -. DR InParanoid; Q9Y287; -. DR OMA; YFAFQQD; -. DR OrthoDB; 3664639at2759; -. DR PhylomeDB; Q9Y287; -. DR TreeFam; TF317770; -. DR PathwayCommons; Q9Y287; -. DR Reactome; R-HSA-977225; Amyloid fiber formation. DR SignaLink; Q9Y287; -. DR BioGRID-ORCS; 9445; 44 hits in 1162 CRISPR screens. DR ChiTaRS; ITM2B; human. DR GeneWiki; ITM2B; -. DR GenomeRNAi; 9445; -. DR Pharos; Q9Y287; Tbio. DR PRO; PR:Q9Y287; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; Q9Y287; Protein. DR Bgee; ENSG00000136156; Expressed in renal glomerulus and 206 other cell types or tissues. DR ExpressionAtlas; Q9Y287; baseline and differential. DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030660; C:Golgi-associated vesicle membrane; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0031090; C:organelle membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0001540; F:amyloid-beta binding; IPI:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IEA:Ensembl. DR GO; GO:0042985; P:negative regulation of amyloid precursor protein biosynthetic process; IDA:UniProtKB. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR InterPro; IPR007084; BRICHOS_dom. DR InterPro; IPR040145; ITM2. DR PANTHER; PTHR10962:SF4; INTEGRAL MEMBRANE PROTEIN 2B; 1. DR PANTHER; PTHR10962; INTEGRAL TRANSMEMBRANE PROTEIN 2; 1. DR Pfam; PF04089; BRICHOS; 1. DR SMART; SM01039; BRICHOS; 1. DR PROSITE; PS50869; BRICHOS; 1. DR Genevisible; Q9Y287; HS. PE 1: Evidence at protein level; KW Alternative splicing; Amyloid; Amyloidosis; Cell membrane; KW Cleavage on pair of basic residues; Deafness; Disease variant; KW Disulfide bond; Endosome; Glycoprotein; Golgi apparatus; Membrane; KW Neurodegeneration; Reference proteome; Secreted; Signal-anchor; KW Transmembrane; Transmembrane helix. FT CHAIN 1..266 FT /note="Integral membrane protein 2B" FT /id="PRO_0000045840" FT CHAIN 1..243 FT /note="BRI2, membrane form" FT /id="PRO_0000417464" FT CHAIN 1..? FT /note="BRI2 intracellular domain" FT /id="PRO_0000417465" FT CHAIN ?..243 FT /note="BRI2C, soluble form" FT /id="PRO_0000417466" FT PEPTIDE 244..266 FT /note="Bri23 peptide" FT /id="PRO_0000016545" FT TOPO_DOM 1..54 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 55..75 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 76..266 FT /note="Lumenal" FT /evidence="ECO:0000255" FT DOMAIN 137..231 FT /note="BRICHOS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00255" FT REGION 102..134 FT /note="Necessary for interaction with APP and inhibitor FT effects on APP processing" FT SITE 243..244 FT /note="Cleavage; by furin" FT CARBOHYD 170 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:21752865" FT DISULFID 89 FT /note="Interchain" FT DISULFID 164..223 FT /evidence="ECO:0000250" FT DISULFID 248..265 FT /note="Interchain (between ADan peptide variants)" FT VAR_SEQ 83..188 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_055326" FT VARIANT 15 FT /note="A -> T (in dbSNP:rs11556905)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5" FT /id="VAR_071047" FT VARIANT 261 FT /note="E -> A (in RDGCA; dbSNP:rs606231283)" FT /evidence="ECO:0000269|PubMed:24026677" FT /id="VAR_072434" FT VARIANT 266 FT /note="S -> FNLFLNSQEKHY (in CAA-ITM2B2; amyloid ADan; FT colocalizes with APP amyloid-beta protein 42 in parenchymal FT and vascular lesions; interacts with APP amyloid-beta FT protein 42; oligomerizes and is subjected to disulfide bond FT formation; undergoes cyclic pyroglutamate formation on the FT N-terminus Gln residues and is further proteolytically FT cleaved in the cerebral cortex)" FT /evidence="ECO:0000269|PubMed:10781099, FT ECO:0000269|PubMed:14656991, ECO:0000269|PubMed:16091362" FT /id="VAR_010240" FT VARIANT 266 FT /note="S -> SRTVKKNIIEEN (in CAA-ITM2B1; amyloid ABri)" FT /evidence="ECO:0000269|PubMed:10391242, FT ECO:0000269|PubMed:10526337, ECO:0000269|PubMed:14656991" FT /id="VAR_010239" FT MUTAGEN 60 FT /note="G->V: Strongly reduces intramembrane cleavage by FT SPPL2B." FT /evidence="ECO:0000269|PubMed:22194595" FT MUTAGEN 170 FT /note="N->A: Accumulates in intracellular compartments. FT Does not inhibit furin, ADAM10 and SPPL2A extracellular FT proteolytic processing activity." FT /evidence="ECO:0000269|PubMed:21752865" FT MUTAGEN 243..244 FT /note="RE->AA: Inhibits cleavage by furin. Does not prevent FT ADAM10 shedding." FT /evidence="ECO:0000269|PubMed:17965014, FT ECO:0000269|PubMed:19748705" SQ SEQUENCE 266 AA; 30338 MW; 3A7D8CA259F1F627 CRC64; MVKVTFNSAL AQKEAKKDEP KSGEEALIIP PDAVAVDCKD PDDVVPVGQR RAWCWCMCFG LAFMLAGVIL GGAYLYKYFA LQPDDVYYCG IKYIKDDVIL NEPSADAPAA LYQTIEENIK IFEEEEVEFI SVPVPEFADS DPANIVHDFN KKLTAYLDLN LDKCYVIPLN TSIVMPPRNL LELLINIKAG TYLPQSYLIH EHMVITDRIE NIDHLGFFIY RLCHDKETYK LQRRETIKGI QKREASNCFA IRHFENKFAV ETLICS //