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    COX4I2 cytochrome c oxidase subunit 4I2 [ Homo sapiens (human) ]

    Gene ID: 84701, updated on 10-Dec-2024

    Summary

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    Official Symbol
    COX4I2provided by HGNC
    Official Full Name
    cytochrome c oxidase subunit 4I2provided by HGNC
    Primary source
    HGNC:HGNC:16232
    See related
    Ensembl:ENSG00000131055 MIM:607976; AllianceGenome:HGNC:16232
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    COX4; COX4B; COX4-2; COX4L2; COXIV-2; dJ857M17.2
    Summary
    Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It 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 be involved in the regulation and assembly of the complex. This nuclear gene encodes isoform 2 of subunit IV. Isoform 1 of subunit IV is encoded by a different gene, however, the two genes show a similar structural organization. Subunit IV is the largest nuclear encoded subunit which plays a pivotal role in COX regulation. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in placenta (RPKM 32.5), lung (RPKM 10.0) and 6 other tissues See more
    Orthologs
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    Genomic context

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    See COX4I2 in Genome Data Viewer
    Location:
    20q11.21
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (31637912..31645006)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (33362179..33369276)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (30225715..30232809)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:30192859-30193529 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:30193530-30194199 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:30194246-30194824 Neighboring gene Sharpr-MPRA regulatory region 11771 Neighboring gene CRISPRi-validated cis-regulatory element chr20.845 Neighboring gene CRISPRi-validated cis-regulatory element chr20.846 Neighboring gene microRNA 3193 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17686 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:30206543-30207044 Neighboring gene inhibitor of DNA binding 1 Neighboring gene MPRA-validated peak4184 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:30221506-30222006 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:30222007-30222507 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12759 Neighboring gene MPRA-validated peak4185 silencer Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:30249151-30249878 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr20:30251554-30252384 Neighboring gene uncharacterized LOC124904883 Neighboring gene VISTA enhancer hs2050 Neighboring gene BCL2 like 1 Neighboring gene BCL2L1 antisense RNA 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:30285857-30286804 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17690 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17691 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17692 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17693 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:30300575-30301102 Neighboring gene Sharpr-MPRA regulatory region 251

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC. Li JP, et al. Cell Mol Biol Lett, 2022 Sep 5. PMID 36064310, Free PMC Article
    2. The interconversion between monomeric and dimeric bovine heart cytochrome c oxidase. Bolli R, et al. Biochimie, 1985 Jan. PMID 2986725
    3. Isolation, subunit composition, and site of synthesis of human cytochrome c oxidase. Hare JF, et al. Biochemistry, 1980 May 13. PMID 6246917
    4. Effects of hemin on apoptosis, suppression of cytochrome c oxidase gene expression, and bone-marrow toxicity induced by doxorubicin (adriamycin). Papadopoulou LC, et al. Biochem Pharmacol, 1996 Sep 13. PMID 8765469
    5. Transcription of mammalian cytochrome c oxidase subunit IV-2 is controlled by a novel conserved oxygen responsive element. Hüttemann M, et al. FEBS J, 2007 Nov. PMID 17937768

    See all (32) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The ratio of cytochrome c oxidase subunit 4 isoform 4I1 and 4I2 mRNA is changed in permanent atrial fibrillation.
      Title: The ratio of cytochrome c oxidase subunit 4 isoform 4I1 and 4I2 mRNA is changed in permanent atrial fibrillation.
    2. HIF1A transcriptional regulation of COX4I2 impacts angiogenesis in pheochromocytoma.
      Title: HIF1A transcriptional regulation of COX4I2 impacts angiogenesis in pheochromocytoma.
    3. Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC.
      Title: Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC.
    4. Upregulation of COX4-2 via HIF-1alpha in Mitochondrial COX4-1 Deficiency.
      Title: Upregulation of COX4-2 via HIF-1α in Mitochondrial COX4-1 Deficiency.
    5. COX4I2 and PLAT were highly correlated with blood supply in adrenal pheochromocytoma which contribute to angiogenesis in adrenal pheochromocytoma, which could be used as biomarkers to better indicate tumor angiogenesis
      Title: From clinic to mechanism: Proteomics-based assessment of angiogenesis in adrenal pheochromocytoma.
    6. Identification of three transcription factors that bind a conserved responsive element of the COX4I2 gene, namely recombination signal sequence-binding protein Jkappa (RBPJ), coiled-coil-helix-coiled-coil-helix domain 2 (CHCHD2) and CXXC finger protein 5 (CXXC5).
      Title: Oxygen-dependent expression of cytochrome c oxidase subunit 4-2 gene expression is mediated by transcription factors RBPJ, CXXC5 and CHCHD2.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    8. Mutation analysis of COX4I2 is warranted in patients with malabsorption due to exocrine pancreatic insufficiency and in patients with dyserythropoeitic anemia.
      Title: Exocrine pancreatic insufficiency, dyserythropoeitic anemia, and calvarial hyperostosis are caused by a mutation in the COX4I2 gene.
    9. COX4I2 is regulated by a novel oxygen sensitive promoter element (5'-GGACGTTCCCACG-3') conserved in mammals. Gene activity is maximal at 4% oxygen. Lung cytochrome c oxidase (COX) is 2.5 fold more active compared to liver COX, which lacks COX4I2.
      Title: Transcription of mammalian cytochrome c oxidase subunit IV-2 is controlled by a novel conserved oxygen responsive element.
    10. COX4I2 is expressed in the highly oxygenated lung tissue. It is found in all cell types of the lung.
      Title: Mammalian subunit IV isoforms of cytochrome c oxidase.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Pancreatic insufficiency-anemia-hyperostosis syndrome
    MedGen: C2675184 OMIM: 612714 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cytochrome-c oxidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cellular respiration NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in generation of precursor metabolites and energy NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in mitochondrial electron transport, cytochrome c to oxygen IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitochondrial electron transport, cytochrome c to oxygen IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proton transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrial intermembrane space TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    part_of respiratory chain complex IV IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of respiratory chain complex IV IC
    Inferred by Curator
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    cytochrome c oxidase subunit 4 isoform 2, mitochondrial
    Names
    COX IV-2
    cytochrome c oxidase subunit IV-like 2
    NP_115998.2
    XP_005260636.1
    XP_005260637.1
    XP_005260638.1
    XP_054180123.1
    XP_054180124.1
    XP_054180125.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012180.1 RefSeqGene

      Range
      5025..12119
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_032609.3 → NP_115998.2  cytochrome c oxidase subunit 4 isoform 2, mitochondrial

      See identical proteins and their annotated locations for NP_115998.2

      Status: REVIEWED

      Source sequence(s)
      AL117381
      Consensus CDS
      CCDS13187.1
      UniProtKB/Swiss-Prot
      Q6GTF4, Q96KJ9, Q9H0Z4
      UniProtKB/TrEMBL
      H6SG14
      Related
      ENSP00000365243.3, ENST00000376075.4
      Conserved Domains (1) summary
      cd00922
      Location:39 → 164
      Cyt_c_Oxidase_IV; Cytochrome c oxidase subunit IV. Cytochrome c oxidase (CcO), the terminal oxidase in the respiratory chains of eukaryotes and most bacteria, is a multi-chain transmembrane protein located in the inner membrane of mitochondria and the cell membrane of ...

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

      Range
      31637912..31645006
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005260581.4 → XP_005260638.1  cytochrome c oxidase subunit 4 isoform 2, mitochondrial isoform X3

      Conserved Domains (1) summary
      cl02792
      Location:40 → 126
      Cyt_c_Oxidase_IV; Cytochrome c oxidase subunit IV. Cytochrome c oxidase (CcO), the terminal oxidase in the respiratory chains of eukaryotes and most bacteria, is a multi-chain transmembrane protein located in the inner membrane of mitochondria and the cell membrane of ...

    2. XM_005260580.5 → XP_005260637.1  cytochrome c oxidase subunit 4 isoform 2, mitochondrial isoform X2

      Conserved Domains (1) summary
      cl02792
      Location:32 → 125
      Cyt_c_Oxidase_IV; Cytochrome c oxidase subunit IV. Cytochrome c oxidase (CcO), the terminal oxidase in the respiratory chains of eukaryotes and most bacteria, is a multi-chain transmembrane protein located in the inner membrane of mitochondria and the cell membrane of ...

    3. XM_005260579.5 → XP_005260636.1  cytochrome c oxidase subunit 4 isoform 2, mitochondrial isoform X1

      Conserved Domains (1) summary
      pfam02936
      Location:45 → 175
      COX4; Cytochrome c oxidase subunit IV

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060944.1 Alternate T2T-CHM13v2.0

      Range
      33362179..33369276
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054324150.1 → XP_054180125.1  cytochrome c oxidase subunit 4 isoform 2, mitochondrial isoform X3

    2. XM_054324149.1 → XP_054180124.1  cytochrome c oxidase subunit 4 isoform 2, mitochondrial isoform X2

    3. XM_054324148.1 → XP_054180123.1  cytochrome c oxidase subunit 4 isoform 2, mitochondrial isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96KJ9.2 GenPept UniProtKB/Swiss-Prot:Q96KJ9

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