COX4I1 is located on the q arm of chromosome 16 in position 24.1 and has 6 exons.[5] The COX4I1 gene produces a 9.3 kDa protein composed of 83 amino acids.[11][12]COX4I1 is expressed ubiquitously. The protein encoded by COX4I1 belongs to the cytochrome c oxidase IV family. COX4I1 has a transit peptide domain and acetyl and phosphoproteinamino acid modifications.[13][14] It is located at the 3' of the NOC4 (neighbor of COX4) gene in a head-to-head orientation and shares a promoter with it.[5]
Although relatively little is known about the function of COX4I1, mutations in this gene have been associated with mitochondrial complex IV diseases with severe phenotypes. Among these, COX deficiency and Fanconi anemia have been suspected and linked to mutations in the COX4I1 gene. Clinical features of pathogenic variants of COX4I1 can include short stature, poor weight gain, mild dysmorphic features, mental retardation, spastic paraplegia, severe epilepsy, a narrow and arched palate, malar hypoplasia, little subcutaneous fat, and arachnodactyly. The homozygous mutation K101N and a de novo 16q24.1 interstitial duplication have been found to cause defective COX4I1.[9][10]
COX4I1 has 153 protein-protein interactions with 142 of them being co-complex interactions. COX4I1 has been found to interact with SDCBP, MT-CO1, IKBKE, TMBIM4, and MCL1.[16]
LON, a mitochondrial protease, has also been suggested to regulate the COX4 subunit isoforms by degrading COX4I1 under hypoxic conditions.[15]
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^Lomax MI, Welch MD, Darras BT, Francke U, Grossman LI (February 1990). "Novel use of a chimpanzee pseudogene for chromosomal mapping of human cytochrome c oxidase subunit IV". Gene. 86 (2): 209–16. doi:10.1016/0378-1119(90)90281-U. PMID2157630.
Van Kuilenburg AB, Van Beeumen JJ, Demol H, Van den Bogert C, Schouten I, Muijsers AO (February 1992). "Subunit IV of human cytochrome c oxidase, polymorphism and a putative isoform". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1119 (2): 218–24. doi:10.1016/0167-4838(92)90395-T. PMID1311608.
Romero N, Marsac C, Fardeau M, Droste M, Schneyder B, Kadenbach B (1990). "Immunohistochemical demonstration of fibre type-specific isozymes of cytochrome c oxidase in human skeletal muscle". Histochemistry. 94 (2): 211–5. doi:10.1007/BF02440190. PMID2162812. S2CID33365867.
Hüttemann M, Kadenbach B, Grossman LI (April 2001). "Mammalian subunit IV isoforms of cytochrome c oxidase". Gene. 267 (1): 111–23. doi:10.1016/S0378-1119(01)00385-7. PMID11311561.
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