COX15

Protein identityUniProt · HPA

UniProt accession

Q7KZN9

Gene

COX15

Ensembl

ENSG00000014919

Chromosome

10

Canonical length

410 aa

Protein class

Disease related genes, Human disease related genes, Potential drug targets, Predicted membrane proteins, Transporters

Subcellular location

Nucleoplasm,Mitochondria

OverviewNCBI Gene

Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes a protein which is not a structural subunit, but may be essential for the biogenesis of COX formation and may function in the hydroxylation of heme O, according to the yeast mutant studies. This protein is predicted to contain 5 transmembrane domains localized in the mitochondrial inner membrane. Alternative splicing of this gene generates two transcript variants diverging in the 3' region. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

410 residues, UniProt reviewed canonical sequence.

>Q7KZN9|COX15
     1  MQRLLFPPLR ALKGRQYLPL LAPRAAPRAQ CDCIRRPLRP GQYSTISEVA LQSGRGTVSL
    61  PSKAAERVVG RWLLVCSGTV AGAVILGGVT RLTESGLSMV DWHLIKEMKP PTSQEEWEAE
   121  FQRYQQFPEF KILNHDMTLT EFKFIWYMEY SHRMWGRLVG LVYILPAAYF WRKGWLSRGM
   181  KGRVLALCGL VCFQGLLGWY MVKSGLEEKS DSHDIPRVSQ YRLAAHLGSA LVLYCASLWT
   241  SLSLLLPPHK LPETHQLLQL RRFAHGTAGL VFLTALSGAF VAGLDAGLVY NSFPKMGESW
   301  IPEDLFTFSP ILRNVFENPT MVQFDHRILG ITSVTAITVL YFLSRRIPLP RRTKMAAVTL
   361  LALAYTQVGL GISTLLMYVP TPLAATHQSG SLALLTGALW LMNELRRVPK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against COX15 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

8

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

25 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about COX15.

Disease | AllUniProt

Conditions COX15 is implicated in, by any mechanism.

• Mitochondrial complex IV deficiency, nuclear type 6 (MC4DN6) MIM:615119

Disease | GeneticClinVar

44 pathogenic / likely-pathogenic of 505 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2
• Leigh syndrome
• Inborn genetic diseases
• See cases
• COX15-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.33

gnomAD pLI

0

gnomAD missense Z

0.26

DepMap mean gene effect

-0.3

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cytochrome complex assembly
• heme A biosynthetic process
• heme biosynthetic process

Molecular functions

• heme binding
• metal ion binding
• oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor
• heme A synthase activity
• oxidoreductase activity, acting on the CH-CH group of donors

Cellular components

• cytochrome complex
• mitochondrial inner membrane
• mitochondrion
• nucleoplasm
• respiratory chain complex

Protein domainsUniProt · Pfam · InterPro

• Peptidase S1, PA clan
• COX15/CtaA family
• Heme A synthase, type 2
• Cytochrome oxidase assembly protein

KeywordsUniProt

• Heme biosynthesis
• Iron
• Leigh syndrome
• Membrane
• Metal-binding
• Mitochondrion
• Mitochondrion inner membrane
• Oxidoreductase
• Primary mitochondrial disease
• Transmembrane
• Transmembrane helix