. 2019 Aug 27;9:12442. doi: 10.1038/s41598-019-48866-y

Table 2.

Comparison of characterized HHD mutant phenotypes in mammalian hosts and yeast.

	Ca²⁺ binding^a	Mn²⁺ binding^a	Auto-phosphorylation	ATPase activity^b,c		Localization^a,b,d		Protein accumulation^a	mRNA accumulation^a
	Ca²⁺ binding^a	Mn²⁺ binding^a	Auto-phosphorylation	Ca²⁺	Mn²⁺	Homozygous	Heterozygous^d	Protein accumulation^a	mRNA accumulation^a
G309C	+/ND	0/ ND	0^b,c/ND	0/+	ND/0	ND/Vacuole	Golgi/Golgi	++/++	++/ND
C344Y	ND/ND	ND/ND	ND/ND	ND/++	ND/+	ND/Golgi	Golgi/Golgi	+/+	++/ND
C411R	ND/ND	ND/ND	ND/ND	ND/+	ND/0	ND/Golgi	Golgi/Golgi	+/+	++/ND
T570I	ND/ND	ND/ND	ND/ND	ND/+	ND/0	ND/Golgi	Golgi/Golgi	+/+	++/ND
I580V	++/ND	++/ND	++^b,c/ND	++/++	ND/++	ND/Vacuole	Golgi/Golgi	++/++	++/ND
D742Y	0/ND	0/ND	0^b/ND	ND/+	ND/0	ND/Vacuole	Golgi/Golgi	++/++	++/ND
G789R	ND/ND	ND/ND	ND/ND	ND/0	ND/0	ND/Golgi	Golgi/Golgi	+/+	++/ND

Values: ND, Not determined; 0, background or marginally above background; +, intermediary; ++, wt level. ^aData for mammalian host (COS-1 cells) obtained from Fairclough et al.¹¹ (SPCA1d). ^bData for mammalian host (HEK293T cells) obtained from Smaardijk et al.⁶⁶. ^cFor comparison with transiently transfected COS-1 cells¹¹ or HEK293T cells⁶⁶ only yeast data for high copy number in liquid media were included. ^dMammalian hosts carry at least one functional ATP2C1 and ATP2A2 allele (as these are not knocked out in the experiments by Fairclough et al. and Smaardijk et al.^11,66), and are as such heterozygous when transfected with vectors carrying wt or HHD ATP2C1. For yeast (our assays) “heterozygous” denotes both wt ATP2C1a/HHD mutant co-expression and ATP2A2b/HHD mutant co-expression as no difference in localization of the GFP tagged HHD-SPCA1a was observed between the two experiments. All data are given as mammalian cells/yeast.