The organelles within secretory and endocytotic pathways in mammalian cells have acidified lumens, and regulation of their acidic pH is critical for the trafficking, processing and glycosylation of cargo proteins and lipids, as well as the morphological integrity of the organelles. Maeda et al. (2008) described a novel protein involved in Golgi acidification. Mutant cells defective in Golgi acidification exhibited delayed protein transport, impaired glycosylation and Golgi disorganization. Using expression cloning, a novel Golgi-resident multi-transmembrane protein, named Golgi pH regulator (GPHR), was identified. After reconstitution in planar lipid bilayers, GPHR exhibited voltage-dependent anion-channel activity that may function in counterion conductance. Thus, GPHR modulates Golgi functions through regulation of acidification. It is reported to be homologous to the G-protein coupled receptor 89B of humans (NP_057418). Its function is reviewed by Edwards and Kahl (2010). It has a central DUF3735 domain, a C-terminal ABA_GREP domain, and 9 putative TMSs.

1.A.38 The Golgi pH Regulator (GPHR) Family The organelles within secretory and endocytotic pathways in mammalian cells have acidified lumens, and regulation of their acidic pH is critical for the trafficking, processing and glycosylation of cargo proteins and lipids, as well as the morphological integrity of the organelles. Maeda et al. (2008) described a novel protein involved in Golgi acidification. Mutant cells defective in Golgi acidification exhibited delayed protein transport, impaired glycosylation and Golgi disorganization. Using expression cloning, a novel Golgi-resident multi-transmembrane protein, named Golgi pH regulator (GPHR), was identified. After reconstitution in planar lipid bilayers, GPHR exhibited voltage-dependent anion-channel activity that may function in counterion conductance. Thus, GPHR modulates Golgi functions through regulation of acidification. It is reported to be homologous to the G-protein coupled receptor 89B of humans (NP_057418). Its function is reviewed by Edwards and Kahl (2010). It has a central DUF3735 domain, a C-terminal ABA_GREP domain, and 9 putative TMSs.
References:
Edwards JC. and Kahl CR. (2010). Chloride channels of intracellular membranes. FEBS Lett. 584(10):2102-11.
Ma, Y., X. Dai, Y. Xu, W. Luo, X. Zheng, D. Zeng, Y. Pan, X. Lin, H. Liu, D. Zhang, J. Xiao, X. Guo, S. Xu, Y. Niu, J. Jin, H. Zhang, X. Xu, L. Li, W. Wang, Q. Qian, S. Ge, and K. Chong. (2015). COLD1 confers chilling tolerance in rice. Cell 160: 1209-1221.
Maeda, Y., T. Ide, M. Koike, Y. Uchiyama, and T. Kinoshita. (2008). GPHR is a novel anion channel critical for acidification and functions of the Golgi apparatus. Nat. Cell Biol. 10: 1135-1145.
Examples:
TC#	Name	Organismal Type	Example
1.A.38.1.1	The Golgi pH regulator, GPHR, of 455 aas and 9 TMSs in a 5 + 4 TMS arrangement.	Animals	*GPHR of Cricetulus griseus* (B2ZXD5)**

1.A.38.1.2	Uncharacterized protein of 367 aas and 8 TMSs.		UP of Entamoeba histolytica

1.A.38.1.3	The GPCR-type G protein, COLD1, of 455 aas and 9 TMSs in a 5 + 4 TMS arrangement. In cold tolerant cultivars (AC Q7X7S8) Met-187 is replaced by Lys-187. This polymorphism is associated with divergence in chilling tolerance of rice cultivars. COLD1 confers adaptation of japonica rice to chilling and originated from the Chinese wild populations of Oryza rufipogon (Ma et al. 2015). Overexpression of COLD1(jap) significantly enhances chilling tolerance, whereas rice lines with a deficiency or downregulation of COLD1(jap) are sensitive to cold. COLD1 encodes a regulator of G-protein signaling that localizes to the plasma membrane and endoplasmic reticulum (ER). It interacts with the G-protein α subunit to activate the Ca²⁺ channel for sensing low temperature and to accelerate G-protein GTPase activity (Ma et al. 2015).		*COLD1 of Oryza sativa* subsp. indica (Rice)**

Examples:
TC#	Name	Organismal Type	Example
1.A.38.2.1	10 TMS homologue (826 aas)	Euglenozoa	*10 TMS homologue of Leishmania mexicana* (E9AL43)**

Examples:
TC#	Name	Organismal Type	Example
1.A.38.3.1	4-5 TMS homologue (398 aas)	Alveolata	*4-5 TMS homologue of Plasmodium yoelii* (Q7RQA4)**