ITM2B
entrez
9445
canonical
uniprot
Q9Y287
canonical
ensembl
ENSG00000136156
resolver
ensp
ENSP00000497221
resolver
genesymbol
ITM2B
resolver
genesymbol_syn
BRI
resolver
genesymbol_syn
BRI2
resolver
hgnc
HGNC:6174
resolver
uniprot
A0A384MDP7
resolver
uniprot
Q5W0A3
resolver
uniprot
Q96B24
resolver
uniprot
Q9NYH1
resolver
uniprot_entry
A0A384MDP7_HUMAN
resolver
uniprot_entry
ITM2B_HUMAN
resolver
uniprot_sec
Q5W0A3
resolver
uniprot_sec
Q96B24
resolver
uniprot_sec
Q9NYH1
resolver
amino_acid_sequence
MVKVTFNSALAQKEAKKDEPKSGEEALIIPPDAVAVDCKDPDDVVPVGQRRAWCWCMCFGLAFMLAGVILGGAYLYKYFALQPDDVYYCGIKYIKDDVILNEPSADAPAALYQTIEENIKIFEEEEVEFISVPVPEFADSDPANIVHDFNKKLTAYLDLNLDKCYVIPLNTSIVMPPRNLLELLINIKAGTYLPQSYLIHEHMVITDRIENIDHLGFFIYRLCHDKETYKLQRRETIKGIQKREASNCFAIRHFENKFAVETLICS
uniprot
proteins
disease_involvement
DISEASE: Cerebral amyloid angiopathy, ITM2B-related 1 (CAA-ITM2B1) [MIM:176500]: 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. {ECO:0000269|PubMed:10391242, ECO:0000269|PubMed:10526337, ECO:0000269|PubMed:14656991}. Note=The disease is caused by variants 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:10391242). ABri accumulates in the brain and produces amyloid fibrils responsible for neuronal dysfunction and dementia. ABri peptide variant forms fibrils in vitro (PubMed:10526337). {ECO:0000269|PubMed:10391242, ECO:0000269|PubMed:10526337}.; DISEASE: Cerebral amyloid angiopathy, ITM2B-related 2 (CAA-ITM2B2) [MIM:117300]: 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. {ECO:0000269|PubMed:10781099, ECO:0000269|PubMed:14656991, ECO:0000269|PubMed:16091362}. Note=The disease is caused by variants 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:10781099). 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. {ECO:0000269|PubMed:10781099}.; DISEASE: Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities (RDGCA) [MIM:616079]: 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. {ECO:0000269|PubMed:24026677}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Plays a regulatory role in the processing of the amyloid-beta A4 precursor protein (APP) and acts as an inhibitor of the amyloid-beta 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 amyloid-beta A4 precursor protein (APP) processing leading to a strong reduction in the secretion of secretase-processed amyloid-beta protein 40 and amyloid-beta protein 42.; FUNCTION: Bri23 peptide prevents aggregation of APP amyloid-beta protein 42 into toxic oligomers.
uniprot
proteins
mass_dalton
30338
uniprot
proteins
mutagenesis
MUTAGEN 60; /note="G->V: Strongly reduces intramembrane cleavage by SPPL2B."; /evidence="ECO:0000269|PubMed:22194595"; MUTAGEN 170; /note="N->A: Accumulates in intracellular compartments. Does not inhibit furin, ADAM10 and SPPL2A extracellular proteolytic processing activity."; /evidence="ECO:0000269|PubMed:21752865"; MUTAGEN 243..244; /note="RE->AA: Inhibits cleavage by furin. Does not prevent ADAM10 shedding."; /evidence="ECO:0000269|PubMed:17965014, ECO:0000269|PubMed:19748705
uniprot
proteins
post_translational_modification
PTM: The ectodomain C-terminal part of the imBRI2 is processed by furin producing a secreted Bri23 peptide and a mature BRI2, membrane form (mBRI2). The remaining part of the ectodomain of mBRI2 containing the BRICHOS domain is cleaved by ADAM10 and is secreted (BRI2C, soluble form). The membrane-bound N-terminal fragment (BRI2C, membrane form) is further proteolytically processed by SPPL2A and SPPL2B through regulated intramembrane proteolysis producing a secreted C-peptide and a BRI2 intracellular domain (BRI2 ICD) released in the cytosol. Shedding by ADAM10 facilitates intramembrane cleavage but is not absolutely required for BRI2 ICD generation.; PTM: Glycosylation at Asn-170 is important for cell surface localization, but doesn't affect furin- and ADAM10-induced proteolytic processing. {ECO:0000269|PubMed:21752865}.
uniprot
proteins
protein_family
ITM2 family
uniprot
proteins
pubmed
10391242
uniprot
proteins
pubmed
10526337
uniprot
proteins
pubmed
10781099
uniprot
proteins
pubmed
10931946
uniprot
proteins
pubmed
14656991
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15983050
uniprot
proteins
pubmed
16027166
uniprot
proteins
pubmed
16091362
uniprot
proteins
pubmed
17965014
uniprot
proteins
pubmed
18440095
uniprot
proteins
pubmed
18524908
uniprot
proteins
pubmed
18753367
uniprot
proteins
pubmed
19114711
uniprot
proteins
pubmed
19748705
uniprot
proteins
pubmed
20036644
uniprot
proteins
pubmed
21752865
uniprot
proteins
pubmed
22170863
uniprot
proteins
pubmed
22194595
uniprot
proteins
pubmed
24026677
uniprot
proteins
sequence_length
266
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Integral membrane protein 2B]: Golgi apparatus membrane {ECO:0000269|PubMed:14656991, ECO:0000269|PubMed:19114711}; Single-pass type II membrane protein {ECO:0000269|PubMed:10526337}. Note=Immature BRI2 (imBRI2) is cleaved by furin in the Golgi into mBRI2 and a Bri23 peptide. mBRI2 is transported to the plasma membrane and Bri23 peptide is secreted.; SUBCELLULAR LOCATION: [BRI2, membrane form]: Cell membrane {ECO:0000269|PubMed:18440095, ECO:0000269|PubMed:19748705, ECO:0000269|PubMed:21752865}; Single-pass type II membrane protein {ECO:0000269|PubMed:10526337}. Endosome membrane {ECO:0000269|PubMed:19748705}; Single-pass type II membrane protein {ECO:0000269|PubMed:10526337}. Note=Mature BRI2 (mBRI2) needs to be transported from the endoplasmic reticulum compartment to the cell membrane in order to be able to inhibit APP processing. {ECO:0000269|PubMed:19748705}.; SUBCELLULAR LOCATION: [Bri23 peptide]: Secreted {ECO:0000269|PubMed:10526337, ECO:0000269|PubMed:14656991, ECO:0000269|PubMed:18524908}. Note=Detected in the cerebral spinal fluid (CSF). {ECO:0000269|PubMed:18524908}.; SUBCELLULAR LOCATION: [BRI2C, soluble form]: Secreted {ECO:0000269|PubMed:17965014}.
uniprot
proteins
transmembrane_region
TRANSMEM 55..75; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins