ID   ITM2B_RAT               Reviewed;         266 AA.
AC   Q5XIE8;
DT   24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 1.
DT   24-JAN-2024, entry version 118.
DE   RecName: Full=Integral membrane protein 2B;
DE   AltName: Full=Immature BRI2;
DE            Short=imBRI2;
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Heart;
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).
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       Interacts with ADAM7 in sperm; the interaction increases following
CC       capacitation (By similarity). {ECO:0000250,
CC       ECO:0000250|UniProtKB:O89051}.
CC   -!- INTERACTION:
CC       Q5XIE8; P31016: Dlg4; NbExp=5; IntAct=EBI-15348306, EBI-375655;
CC       Q5XIE8; P07936: Gap43; NbExp=3; IntAct=EBI-15348306, EBI-26438795;
CC       Q5XIE8; P07825: Syp; NbExp=4; IntAct=EBI-15348306, EBI-976085;
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; BC083735; AAH83735.1; -; mRNA.
DR   RefSeq; NP_001006964.1; NM_001006963.1.
DR   AlphaFoldDB; Q5XIE8; -.
DR   SMR; Q5XIE8; -.
DR   BioGRID; 253181; 512.
DR   IntAct; Q5XIE8; 512.
DR   MINT; Q5XIE8; -.
DR   STRING; 10116.ENSRNOP00000023037; -.
DR   GlyCosmos; Q5XIE8; 1 site, No reported glycans.
DR   GlyGen; Q5XIE8; 1 site.
DR   iPTMnet; Q5XIE8; -.
DR   PhosphoSitePlus; Q5XIE8; -.
DR   SwissPalm; Q5XIE8; -.
DR   jPOST; Q5XIE8; -.
DR   PaxDb; 10116-ENSRNOP00000023037; -.
DR   Ensembl; ENSRNOT00000023037.6; ENSRNOP00000023037.3; ENSRNOG00000016271.6.
DR   Ensembl; ENSRNOT00055025233; ENSRNOP00055020634; ENSRNOG00055014728.
DR   Ensembl; ENSRNOT00060031957; ENSRNOP00060025980; ENSRNOG00060018579.
DR   Ensembl; ENSRNOT00065014391; ENSRNOP00065010786; ENSRNOG00065009003.
DR   GeneID; 290364; -.
DR   KEGG; rno:290364; -.
DR   UCSC; RGD:620727; rat.
DR   AGR; RGD:620727; -.
DR   CTD; 9445; -.
DR   RGD; 620727; Itm2b.
DR   eggNOG; KOG4681; Eukaryota.
DR   GeneTree; ENSGT00950000183115; -.
DR   HOGENOM; CLU_074596_0_0_1; -.
DR   InParanoid; Q5XIE8; -.
DR   OMA; YFAFQQD; -.
DR   OrthoDB; 3664639at2759; -.
DR   PhylomeDB; Q5XIE8; -.
DR   TreeFam; TF317770; -.
DR   PRO; PR:Q5XIE8; -.
DR   Proteomes; UP000002494; Chromosome 15.
DR   Bgee; ENSRNOG00000016271; Expressed in Ammon's horn and 20 other cell types or tissues.
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; IBA:GO_Central.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0030660; C:Golgi-associated vesicle membrane; ISS:UniProtKB.
DR   GO; GO:0031090; C:organelle membrane; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0001540; F:amyloid-beta binding; ISO:RGD.
DR   GO; GO:0005524; F:ATP binding; ISO:RGD.
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: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; Q5XIE8; RN.
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_0000154824"
FT   CHAIN           1..243
FT                   /note="BRI2, membrane form"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000417487"
FT   CHAIN           1..?
FT                   /note="BRI2 intracellular domain"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000417488"
FT   CHAIN           ?..243
FT                   /note="BRI2C, soluble form"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000417489"
FT   PEPTIDE         244..266
FT                   /note="Bri23 peptide"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000417490"
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;  30314 MW;  E3925091C653C449 CRC64;
     MVKVTFNSAL AQKEAKKDEP KSSEEALIAP PDAVAVDCKD PDDVVPVGQR RAWCWCMCFG
     LAFMLAGVIL GGAYLYKYFA LQPDDVYYCG LKYIKDDVIL SEPSADAPAA RYQTIEENIK
     IFEEDAVEFI SVPVPEFADS DPANIVHDFN KKLTAYLDLN LDKCYVIPLN TSIVMPPRNL
     LELLINIKAG TYLPQSYLIH EHMVITDRIE NVDHLGFFIY RLCHDKETYK LQRRETIRGI
     QKREASNCFT IRHFENKFAV ETLICS
//