1.A.74 The Mitsugumin 23 (MG23) Family Mitsugumin 23 (MG23) is a 23 kDa transmembrane protein (homologous to the Bri3 protein) localized to the sarcoplasmic/endoplasmic reticulum and nuclear membranes in a wide variety of organisms and all types (Venturi et al., 2011). Venturi et al. (2011) reported the biochemical and biophysical characterization of MG23. Hydropathicity profile and limited proteolytic analysis proposed three - five transmembrane segments and a homo-oligomeric assembly. Ultrastructural observations detected a large symmetrical particle as the predominant component and a small asymmetric assembly as the second major component in purified MG23 preparations. Single-particle three-dimensional reconstruction revealed that MG23 forms a large bowl-shaped complex equipped with a putative central pore, which may be an assembly of the small asymmetric subunit. After reconstitution into planar phospholipid bilayers, purified MG23 behaved as a voltage-dependent, cation-conducting channel, permeable to both K⁺ and Ca²⁺. Multiple channels appeared to gate together. The bowl-shaped MG23 can transiently assemble and disassemble, allowing rapid cationic flux across intracellular membrane systems.
References:
Matsuda, S., Y. Matsuda, and L. D''Adamio. (2009). BRI3 inhibits amyloid precursor protein processing in a mechanistically distinct manner from its homologue dementia gene BRI2. J. Biol. Chem. 284: 15815-15825.
Reilly-O''Donnell, B., G.B. Robertson, A. Karumbi, C. McIntyre, W. Bal, M. Nishi, H. Takeshima, A.J. Stewart, and S.J. Pitt. (2017). Dysregulated Zn²⁺ homeostasis impairs cardiac type-2 ryanodine receptor and mitsugumin 23 functions, leading to sarcoplasmic reticulum Ca²⁺ leakage. J. Biol. Chem. [Epub: Ahead of Print]
Takeshima, H., E. Venturi, and R. Sitsapesan. (2015). New and notable ion-channels in the sarcoplasmic/endoplasmic reticulum: do they support the process of intracellular Ca²⁺ release? J. Physiol. 593: 3241-3251.
Venturi, E., K. Mio, M. Nishi, T. Ogura, T. Moriya, S.J. Pitt, K. Okuda, S. Kakizawa, R. Sitsapesan, C. Sato, and H. Takeshima. (2011). Mitsugumin 23 forms a massive bowl-shaped assembly and cation-conducting channel. Biochemistry 50: 2623-2632.
Examples:
TC#	Name	Organismal Type	Example
1.A.74.1.1	Mitsugumin 23 (MG23), also called TM protein 109 (Venturi et al., 2011). MG23 is a Ca2+ channel protein that is regulated by cytoplasmic Zn²⁺, and dysregulation of this ion channel plays a role in diastolic sarcoplasmic reticulum Ca²⁺ homeostasis, promoting leakage from the SR (Reilly-O'Donnell et al. 2017).	Animals	*MG23 of Mus musculus* (Q3UBX0)**

1.A.74.1.2	*Mitsugumin23 (TMEM109) of 243 aas and 5 TMSs (Takeshima et al.* 2015).**		Mitsugumin23 of Homo sapiens

Examples:
TC#	Name	Organismal Type	Example
1.A.74.2.1	Bri3 binding protein, isoform CRA_a	Animals	*Bri3 of Mus musculus* (Q8BXV2)**

1.A.74.2.2	BRI3 binding protein. Plays a role in tumorigenesis. BRI3 is a member of the BRI gene family that includes the familial British and Danish dementia gene BRI2. BRI3 interacts with the Amyloid Precursor Protein, APP, and serves as an endogenous negative regulator of Abeta production (Matsuda et al. 2009).		BRI3 BP of Homo sapiens

Examples:
TC#	Name	Organismal Type	Example
1.A.74.3.1	Uncharacterized protein of 234 aas and 5 TMSs		UP of Tetraodon nigroviridis (Spotted green pufferfish) (Chelonodon nigroviridis)