8.A.82.1.10
Calcium and integrin-binding family member 2, CIB2 or KIP2, of 187 aas.  It is a calcium-binding protein critical for proper photoreceptor cell maintenance and function. It plays a role in intracellular calcium homeostasis by decreasing ATP-induced calcium release (Riazuddin et al. 2012, Seco et al. 2016, Patel et al. 2015). It is essential for mechanotransduction. CIB3 (TC# 8.A.82.1.11) is functionally and structurally equivalent to CIB2 (Liang et al. 2021). CIB2 and CIB3 are structurally similar to KChIP proteins, auxiliary subunits of voltage-gated Kv4 channels. CIB2 and CIB3 bind to TMC1/2 through a domain in TMC1/2 flanked by TMSs 2 and 3. The co-crystal structure of the CIB-binding domain in TMC1 with CIB3 revealed that interactions are mediated through a conserved CIB hydrophobic groove, similar to KChIP1 binding of Kv4. Functional studies in mice showed that CIB2 regulates TMC1/2 localization and function in hair cells, processes that are affected by deafness-causing CIB2 mutations. Thus, CIB2 and CIB3 are MET channel auxiliary subunits with striking similarity to Kv4 channel auxiliary subunits (Liang et al. 2021). CIB3 or KIP3 is 61% identical to CIB2 and is the same length. Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels (Giese et al. 2023).