ITM2B_MOUSE
ID ITM2B_MOUSE Reviewed; 266 AA.
AC O89051; Q545S7;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 169.
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9795190; DOI=10.1016/s0378-1119(98)00354-0;
RA Pittois K., Deleersnijder W., Merregaert J.;
RT "cDNA sequence analysis, chromosomal assignment and expression pattern of
RT the gene coding for integral membrane protein 2B.";
RL Gene 217:141-149(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=10679242; DOI=10.1006/bbrc.2000.2170;
RA Inoue S., Sano H., Ohta M.;
RT "Growth suppression of Escherichia coli by induction of expression of
RT mammalian genes with transmembrane or ATPase domains.";
RL Biochem. Biophys. Res. Commun. 268:553-561(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Head, Hippocampus, and Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By similarity).
CC {ECO:0000250}.
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. {ECO:0000250}.
CC -!- FUNCTION: Bri23 peptide prevents aggregation of APP amyloid-beta
CC protein 42 into toxic oligomers. {ECO:0000250}.
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 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Integral membrane protein 2B]: Golgi apparatus
CC membrane {ECO:0000250|UniProtKB:Q9Y287}; Single-pass type II membrane
CC protein {ECO:0000250|UniProtKB:Q9Y287}. Note=Immature BRI2 (imBRI2) is
CC cleaved by furin in the Golgi into mBRI2 and a Bri23 peptide. mBRI2 is
CC transported to the plasma membrane and Bri23 peptide is secreted.
CC {ECO:0000250|UniProtKB:Q9Y287}.
CC -!- SUBCELLULAR LOCATION: [BRI2, membrane form]: Cell membrane
CC {ECO:0000250|UniProtKB:Q9Y287}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9Y287}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q9Y287}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9Y287}. 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:0000250|UniProtKB:Q9Y287}.
CC -!- SUBCELLULAR LOCATION: [Bri23 peptide]: Secreted
CC {ECO:0000250|UniProtKB:Q9Y287}. Note=Detected in the cerebral spinal
CC fluid (CSF). {ECO:0000250|UniProtKB:Q9Y287}.
CC -!- SUBCELLULAR LOCATION: [BRI2C, soluble form]: Secreted
CC {ECO:0000250|UniProtKB:Q9Y287}.
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 (By similarity).
CC {ECO:0000250}.
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:0000250}.
CC -!- SIMILARITY: Belongs to the ITM2 family. {ECO:0000305}.
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DR EMBL; U76253; AAC63851.1; -; mRNA.
DR EMBL; AB030203; BAA92766.1; -; mRNA.
DR EMBL; AK002599; BAB22220.1; -; mRNA.
DR EMBL; AK003587; BAB22877.1; -; mRNA.
DR EMBL; AK005125; BAB23828.1; -; mRNA.
DR EMBL; AK076139; BAC36212.1; -; mRNA.
DR EMBL; AK077482; BAC36822.1; -; mRNA.
DR EMBL; AK150378; BAE29510.1; -; mRNA.
DR EMBL; AK151714; BAE30633.1; -; mRNA.
DR EMBL; AK151889; BAE30773.1; -; mRNA.
DR EMBL; AK152068; BAE30922.1; -; mRNA.
DR EMBL; AK152516; BAE31278.1; -; mRNA.
DR EMBL; AK152650; BAE31387.1; -; mRNA.
DR EMBL; AK152731; BAE31452.1; -; mRNA.
DR EMBL; AK152983; BAE31632.1; -; mRNA.
DR EMBL; AK153103; BAE31723.1; -; mRNA.
DR EMBL; AK159340; BAE35002.1; -; mRNA.
DR EMBL; AK159426; BAE35073.1; -; mRNA.
DR EMBL; AK159619; BAE35235.1; -; mRNA.
DR EMBL; AK159628; BAE35242.1; -; mRNA.
DR EMBL; AK159792; BAE35374.1; -; mRNA.
DR EMBL; AK159962; BAE35517.1; -; mRNA.
DR EMBL; AK160725; BAE35970.1; -; mRNA.
DR EMBL; BC004731; AAH04731.1; -; mRNA.
DR EMBL; BC010320; AAH10320.1; -; mRNA.
DR EMBL; BC021786; AAH21786.1; -; mRNA.
DR CCDS; CCDS27269.1; -.
DR RefSeq; NP_032436.1; NM_008410.2.
DR AlphaFoldDB; O89051; -.
DR SMR; O89051; -.
DR BioGRID; 200844; 10.
DR IntAct; O89051; 3.
DR MINT; O89051; -.
DR STRING; 10090.ENSMUSP00000022704; -.
DR GlyConnect; 2394; 2 N-Linked glycans (1 site).
DR GlyGen; O89051; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; O89051; -.
DR PhosphoSitePlus; O89051; -.
DR SwissPalm; O89051; -.
DR CPTAC; non-CPTAC-3585; -.
DR EPD; O89051; -.
DR jPOST; O89051; -.
DR MaxQB; O89051; -.
DR PaxDb; O89051; -.
DR PeptideAtlas; O89051; -.
DR PRIDE; O89051; -.
DR ProteomicsDB; 268907; -.
DR Antibodypedia; 23811; 262 antibodies from 31 providers.
DR DNASU; 16432; -.
DR Ensembl; ENSMUST00000022704; ENSMUSP00000022704; ENSMUSG00000022108.
DR GeneID; 16432; -.
DR KEGG; mmu:16432; -.
DR UCSC; uc007ups.1; mouse.
DR CTD; 9445; -.
DR MGI; MGI:1309517; Itm2b.
DR VEuPathDB; HostDB:ENSMUSG00000022108; -.
DR eggNOG; KOG4681; Eukaryota.
DR GeneTree; ENSGT00950000183115; -.
DR HOGENOM; CLU_074596_0_0_1; -.
DR InParanoid; O89051; -.
DR OMA; YFAFQQD; -.
DR OrthoDB; 1322680at2759; -.
DR PhylomeDB; O89051; -.
DR TreeFam; TF317770; -.
DR BioGRID-ORCS; 16432; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Itm2b; mouse.
DR PRO; PR:O89051; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; O89051; protein.
DR Bgee; ENSMUSG00000022108; Expressed in stroma of bone marrow and 264 other tissues.
DR ExpressionAtlas; O89051; baseline and differential.
DR Genevisible; O89051; MM.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030660; C:Golgi-associated vesicle membrane; ISS:UniProtKB.
DR GO; GO:0031301; C:integral component of organelle membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IDA:MGI.
DR GO; GO:0042985; P:negative regulation of amyloid precursor protein biosynthetic process; ISS:UniProtKB.
DR InterPro; IPR007084; BRICHOS_dom.
DR InterPro; IPR040145; ITM2.
DR PANTHER; PTHR10962; PTHR10962; 1.
DR Pfam; PF04089; BRICHOS; 1.
DR SMART; SM01039; BRICHOS; 1.
DR PROSITE; PS50869; BRICHOS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Endosome; Glycoprotein; Golgi apparatus;
KW Membrane; Reference proteome; Secreted; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..266
FT /note="Integral membrane protein 2B"
FT /id="PRO_0000154822"
FT CHAIN 1..243
FT /note="BRI2, membrane form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417471"
FT CHAIN 1..?
FT /note="BRI2 intracellular domain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417472"
FT CHAIN ?..243
FT /note="BRI2C, soluble form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417473"
FT PEPTIDE 244..266
FT /note="Bri23 peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417474"
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 /evidence="ECO:0000250"
FT SITE 243..244
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000250"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 89
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 164..223
FT /evidence="ECO:0000250"
FT DISULFID 248..265
FT /evidence="ECO:0000250"
SQ SEQUENCE 266 AA; 30260 MW; F3EA640D6E600382 CRC64;
MVKVTFNSAL AQKEAKKDEP KSSEEALIVP PDAVAVDCKD PGDVVPVGQR RAWCWCMCFG
LAFMLAGVIL GGAYLYKYFA LQPDDVYYCG LKYIKDDVIL NEPSADAPAA RYQTIEENIK
IFEEDAVEFI SVPVPEFADS DPANIVHDFN KKLTAYLDLN LDKCYVIPLN TSIVMPPKNL
LELLINIKAG TYLPQSYLIH EHMVITDRIE NVDNLGFFIY RLCHDKETYK LQRRETIRGI
QKREASNCFT IRHFENKFAV ETLICS
