ITM2B_HUMAN » Integral membrane protein 2B

ITM2B_HUMAN » Integral membrane protein 2B
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Topology in Vesicle membrane
Topologyvesicle lumenal side
cytoplasmic side
ITM2B_HUMAN » Integral membrane protein 2B » Immature BRI2;imBRI2; Protein E25B;Transmembrane protein BRI;Bri;
Hydrophobic Thickness 28.4 ± 0.8 Å
Tilt Angle 0 ± 2°
ΔGtransfer -39.5 kcal/mol
ΔGfold -16.3 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology In
TM Segments 53-75 (47-82)
Pathways none
PDB none
OPM none
Complexes none
Interactions

A4, Complex: ITM2B:A4, PubMed

BCL2, Complex: ITM2B:BCL2, PubMed

CREB3, Complex: ITM2B:CREB3

KASH5, Complex: ITM2B:KASH5

NADL2, Complex: ITM2B:NADL2

RYK, Complex: RYK:ITM2B, PubMed

SYNE4, Complex: ITM2B:SYNE4

Domains

AA: 139-230, PDBID: 2YAD, Subunit F, Seq Identity:19%, BRICHOS domain

UniProt annotation for ITM2B_HUMAN » Integral membrane protein 2B
FUNCTION: Plays a regulatory role in the processing of the beta- amyloid A4 precursor protein (APP) and acts as an inhibitor of the beta-amyloid peptide aggregation and fibrils deposition. Plays a role in the induction of neurite outgrowth. Functions as a protease inhibitor by blocking access of secretases to APP cleavage sites.

FUNCTION: Mature BRI2 (mBRI2) functions as a modulator of the beta-amyloid A4 precursor protein (APP) processing leading to a strong reduction in the secretion of secretase-processed beta- amyloid protein 40 and beta-amyloid protein 42.

FUNCTION: Bri23 peptide prevents aggregation of APP beta-amyloid protein 42 peptide into toxic oligomers.

SUBUNIT: 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 beta-amyloid protein 40.

TISSUE SPECIFICITY: Ubiquitous. Expressed in brain.

DISEASE: Cerebral amyloid angiopathy, ITM2B-related 1 (CAA-ITM2B1) OMIM: A disorder characterized by amyloid deposition in the walls of cerebral blood vessels and neurodegeneration in the central nervous system. Cerebral amyloid angiopathy, non-neuritic and perivascular plaques and neurofibrillary tangles are the predominant pathological lesions. Clinical features include progressive mental deterioration, spasticity and muscular rigidity. Note=The disease is caused by mutations affecting the gene represented in this entry. A single base substitution at the stop codon of ITM2B generates a 277-residue precursor that is cleaved at the normal furin processing site to generate the ABri amyloidogenic peptide (PubMed). ABri accumulates in the brain and produces amyloid fibrils responsible for neuronal dysfunction and dementia. ABri peptide variant forms fibrils in vitro (PubMed).

DISEASE: Cerebral amyloid angiopathy, ITM2B-related 2 (CAA-ITM2B2) OMIM: A disorder characterized by amyloid deposition in the walls of the blood vessels of the cerebrum, choroid plexus, cerebellum, spinal cord and retina. Plaques and neurofibrillary tangles are observed in the hippocampus. Clinical features include progressive ataxia, dementia, cataracts and deafness. Note=The disease is caused by mutations affecting the gene represented in this entry. A decamer duplication in the 3" region of ITM2B results in the production of the ADan amyloidogenic peptide (PubMed). ADan is generated by cleavage of the mutated precursor at the normal furin processing site. ADan accumulates in the brain and produces amyloid fibrils responsible for neuronal dysfunction and dementia.

DISEASE: Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities (RDGCA) OMIM: An autosomal dominant retinal dystrophy characterized by inner retinal dysfunction in association with ganglion cell abnormalities. Clinical features include mild photophobia, progressive loss of central vision, night blindness, and hyperreflectivity of nerve and ganglion cell layers. disease is caused by mutations affecting the gene represented in this entry.

UniProt features for ITM2B_HUMAN » Integral membrane protein 2B
CHAIN 1 266 Integral membrane protein 2B.
CHAIN 1 243 BRI2, membrane form.
CHAIN 1 ? BRI2 intracellular domain.
CHAIN ? 243 BRI2C, soluble form.
PEPTIDE 244 266 Bri23 peptide.
DOMAIN 137 231 BRICHOS.
REGION 102 134 Necessary for interaction with APP and inhibitor effects on APP processing.
SITE 243 244 Cleavage; by furin.
DISULFID 89 89 Interchain.
DISULFID 164 223 Probable.
DISULFID 248 265 Interchain (between ADan peptide variants).
Amino Acid Sequence for ITM2B_HUMAN » Integral membrane protein 2B
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