|ITM2B in Human Brain. ITM2B was detected in immersion fixed paraffin-embedded sections of human Alzheimer's brain using Sheep Anti-Human ITM2B Antigen Affinity-purified Polyclonal Antibody (Catalog # AF7015) at 5 µg/mL overnight at 4 °C. Tissue was stained using the Anti-Sheep HRP-DAB Cell & Tissue Staining Kit (brown; Catalog # CTS019) and counterstained with hematoxylin (blue). Specific staining was localized to neurons and plaques. View our protocol for Chromogenic IHC Staining of Paraffin-embedded Tissue Sections.|
ITM2B (Integral membrane protein 2B; also protein E25B and BRI/BRI2) is a 50 kDa member of the ITM2 family of proteins. It is widely expressed, and is involved in APP processing. ITM2B is expressed in the Golgi and on the cell surface, and forms a noncovalent complex with A beta PP. Although both molecules are susceptible to secretase processing, ITM2B appears to block A beta PP cleavage by alpha - and gamma -secretase. Human ITM2B is a 266 amino acid (aa) type II transmembrane protein. The ECD (aa 76-266) contains a propeptide sequence (aa 244-266), one BRICHOS domain (aa 137-231), and a Cys at position 89 that participates in homodimerization. Multiple enzymes can cleave ITM2B. Cleavage of the propeptide by furin generates a 3-4 kDa soluble fragment and a 41-45 kDa transmembrane molecule. Further cleavage of the 44 kDa form in the juxtamembrane and intramembrane regions generates a soluble 24 kDa BRICHOS-containing protein, a 22 kDa N-terminal transmembrane peptide, and a soluble 10 kDa cytoplasmic fragment. There are multiple potential splice variants. Two add different 11 aa sequences to the propeptide, resulting in two different 4-5 kDa, 34 aa fragments being released by furin activity. There is also a deletion of aa 83-188, and a substitution of 21 aa for aa 116-266. Over aa 60-266, human ITM2B shares 96% aa identity with mouse ITM2B.
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