COX4I1

COX4I1
Identifiers
Aliases	COX4I1, COX4, COX4-1, COXIV, COX IV-1, COXIV-1, cytochrome c oxidase subunit 4I1, MC4DN16
External IDs	OMIM: 123864; MGI: 88473; HomoloGene: 37537; GeneCards: COX4I1; OMA:COX4I1 - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q24.1 Start 85,798,633 bp[1] End 85,807,068 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 E1|8 69.99 cM Start 121,394,961 bp[2] End 121,400,946 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart left ventricle right auricle right ventricle prefrontal cortex myocardium of left ventricle middle temporal gyrus right frontal lobe Brodmann area 9 Brodmann area 23 Top expressed in myocardium of ventricle right ventricle Epithelium of choroid plexus soleus muscle extraocular muscle epithelium of stomach brown adipose tissue transitional epithelium of urinary bladder thoracic diaphragm nucleus accumbens More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding cytochrome-c oxidase activity Cellular component mitochondrial inner membrane extracellular exosome membrane mitochondrion nucleus mitochondrial membranes mitochondrial respiratory chain complex IV integral component of membrane Biological process generation of precursor metabolites and energy response to nutrient proton transmembrane transport mitochondrial electron transport, cytochrome c to oxygen electron transport chain Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1327 12857 Ensembl ENSG00000131143 ENSMUSG00000031818 UniProt P13073 Q86WV2 P19783 RefSeq (mRNA) NM_001861 NM_001318786 NM_001318788 NM_001318794 NM_001318797 NM_001318802 NM_001293559 NM_009941 RefSeq (protein) NP_001305715 NP_001305717 NP_001305723 NP_001305726 NP_001305731 NP_001852 NP_001305715.1 NP_001280488 NP_034071 Location (UCSC) Chr 16: 85.8 – 85.81 Mb Chr 8: 121.39 – 121.4 Mb PubMed search [3] [4]
Wikidata
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Cytochrome c oxidase subunit 4 isoform 1, mitochondrial (COX4I1) is an enzyme that in humans is encoded by the COX4I1 gene. COX4I1 is a nuclear-encoded isoform of cytochrome c oxidase (COX) subunit 4. Cytochrome c oxidase (complex IV) is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane, acting as the terminal enzyme of the mitochondrial respiratory chain.^[5][6][7] Antibodies against COX4 can be used to identify the inner membrane of mitochondria in immunofluorescence studies.^[8] Mutations in COX4I1 have been associated with COX deficiency and Fanconi anemia.^[9][10]

Structure

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 phosphoprotein amino 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]

Function

COX4I1 encodes a protein that is located in the inner mitochondrial membrane and is an isoform of the nuclear-encoded subunit IV of cytochrome c oxidase (complex IV), the terminal oxidase in mitochondrial electron transport. Complex IV is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane.^[5] The expression of COX4I1, along with COX4I2, may be regulated by oxygen levels, with reduced levels of oxygen leading to increased COX4I2 expression and COX4I1 degradation. This suggests a role for COX4I1 in the optimization of the electron transfer chain under different conditions.^[15]

Clinical Significance

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]

Interactions

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]

References

External links

• Human COX4I1 genome location and COX4I1 gene details page in the UCSC Genome Browser.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.