Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome coxidase

Table 2 Candidate COX assembly factors

Yeast			Human
Gene	Description	Phase	Gene	Targeting signal	Mitochondrial localization	OXPHOS co-expression
COX14	Negative translation regulation of COX1 translation	HHM	C12orf62	No	+	0.93
COX20	Proteolytic processing of Cox2p and its assembly into COX	Profile	FAM36A	No	+^a	0.63
COX23	Cytochrome oxidase assembly	Sequence	CHCHD7	No	ND	0.63
COX24	Required for accumulation of spliced COX1 mRNA	HMM	AURKAIP1	Yes	+	0.91
COA1	Cytochrome oxidase assembly	HMM	C7orf44	Yes	+	0.73
COA3	Negative regulation of COX1 subunit	HMM	CCDC56	No	+^b	0.92
MSS51	UTR translation COX1 regulation	Profile	ZMYND17	Yes	ND	0.01
PET100	Assembly of COX	Profile	PET100/LOC100131801	No	+^b	ND ^c
PET117	Assembly of COX	Sequence	PET117/LOC100303755	No	+	ND
PET191	Assembly of COX	Sequence	COA5/C2orf64	No	ND ^d	0.55
PET309	Translation activator of COX1	Profile	PTCD1	Yes	ND	0.48
YMR244C-A	Putative protein of unknown function	Sequence	C1orf31	Yes	+²	0.8

Human orthologs of yeast COX assembly factors inferred with Ortho-Profile that have not been previously linked to COX assembly in mammals. The targeting signal is predicted with TargetP [66]. Confirmed mitochondrial localization is marked with a plus sign (+; see also Figure 2). Integrated probability of co-expression with oxidative phosphorylation (OXPHOS) complexes in mammalian cells from [36]; ND, no data. ^aGFP-validated mitochondrial localization; ^bprotein presence in pure mitochondrial fractionations from [11]. ^cCo-expresses with OXPHOS subunits in Drosophila melanogaster (data from STRING 9.0 [69]; Supplemental Methods in Additional file 2). ^dOur study showed that the mutation causes COX assembly defect and mitochondrial cardiomyopathy [32].

ISSN: 1474-760X