| Primary Identifier | IPR017276 | Type | Family |
| Short Name | Synth_of_cyt-c-oxidase_Sco1/2 |
| description | This entry represents cytochrome c oxidase assembly factors Sco1 and Sco2 (Synthesis of Cytochrome c Oxidase, factors 1 and 2), mitochondrial inner membrane-tethered metallochaperones that have regulatory roles in the maintenance of cellular copper homeostasis. These proteins are essential for the assembly of the catalytic core of cytochrome c oxidase (COX or complex IV), as well as other roles in copper homeostasis such as mitochondrial redox signalling []. Both Sco1 and Sco2 contain highly conserved CXXXC motifs thought to be required for copper binidng.COX is the terminal enzyme of the energy transducing respiratory chain in eukaryotes and certain prokaryotes. It catalyses the transfer of electrons from cytochrome c to molecular oxygen and pumps protons across the mitochondrial inner membrane to establish a proton gradient for ATP synthesis. It consists of 12-13 protein subunits, with 3 subunits (Cox1-Cox3) forming the enzyme core. COX uses haem and copper as cofactors: Cox1 contains a 1-copper centre (CuB) that interacts with the haem moiety and Cox2 contains a 2-copper centre (CuA). Sco1 and Sco2 act as copper chaperones, transporting copper to the CuA site in Cox2, and are thought to have cooperative functions in COX assembly [, ]. In addition, human Sco2 is also the downstream mediator of the balance between the utilization of respiratory and glycolytic pathways []and both Sco1 and Sco2 may have regulatory roles in regulating cellular copper levels (homeostasis) []. Sco2 may have a copper-level-detection signalling role, acting upstream and in conjunction with Sco1.Defects in Sco1 are a cause of cytochrome c oxidase deficiency (COX deficiency) (OMIM:220110), a clinically heterogeneous disorder with features ranging from isolated myopathy to severe multisystem disease, and onset from infancy to adulthood. Defects in Sco2 are the cause of fatal infantile cardioencephalomyopathy with cytochrome c oxidase deficiency (FIC) (OMIM:604377, OMIM:220110), which is characterised by hypertrophic cardiomyopathy, lactic acidosis, and gliosis. |
