ITM2B_MACFA
ID ITM2B_MACFA Reviewed; 266 AA.
AC Q60HC1; Q4R8U8; Q8HXY3;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 25-MAY-2022, entry version 69.
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; Synonyms=BRI; ORFNames=QflA-11829, QflA-12336, QtsA-11432;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Frontal cortex;
RA Kusuda J., Osada N., Tanuma R., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation and characterization of cDNA for macaque neurological disease
RT genes.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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; AB083306; BAC20585.1; -; mRNA.
DR EMBL; AB125206; BAD51994.1; -; mRNA.
DR EMBL; AB168350; BAE00473.1; -; mRNA.
DR RefSeq; NP_001270631.1; NM_001283702.1.
DR RefSeq; XP_015294458.1; XM_015438972.1.
DR AlphaFoldDB; Q60HC1; -.
DR STRING; 9541.XP_005585890.1; -.
DR GeneID; 101926229; -.
DR KEGG; mcf:101926229; -.
DR CTD; 9445; -.
DR VEuPathDB; HostDB:ENSMFAG00000036817; -.
DR eggNOG; KOG4681; Eukaryota.
DR OMA; YFAFQQD; -.
DR OrthoDB; 1322680at2759; -.
DR Proteomes; UP000233100; Chromosome 17.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
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:0005886; C:plasma membrane; ISS:UniProtKB.
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 2: Evidence at transcript 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_0000154821"
FT CHAIN 1..243
FT /note="BRI2, membrane form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417467"
FT CHAIN 1..?
FT /note="BRI2 intracellular domain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417468"
FT CHAIN ?..243
FT /note="BRI2C, soluble form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417469"
FT PEPTIDE 244..266
FT /note="Bri23 peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417470"
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"
FT CONFLICT 230
FT /note="K -> I (in Ref. 1; BAC20585)"
FT /evidence="ECO:0000305"
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
