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    COX4I1 cytochrome c oxidase subunit 4I1 [ Homo sapiens (human) ]

    Gene ID: 1327, updated on 10-Jun-2024

    Summary

    Official Symbol
    COX4I1provided by HGNC
    Official Full Name
    cytochrome c oxidase subunit 4I1provided by HGNC
    Primary source
    HGNC:HGNC:2265
    See related
    Ensembl:ENSG00000131143 MIM:123864; AllianceGenome:HGNC:2265
    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; COXIV; COX4-1; COXIV-1; MC4DN16; COX IV-1
    Summary
    Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It 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. The complex consists of 13 mitochondrial- and nuclear-encoded subunits. The mitochondrially-encoded subunits perform the electron transfer and proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex. This gene encodes the nuclear-encoded subunit IV isoform 1 of the human mitochondrial respiratory chain enzyme. 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. Pseudogenes related to this gene are located on chromosomes 13 and 14. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
    Expression
    Ubiquitous expression in heart (RPKM 267.7), duodenum (RPKM 151.5) and 25 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See COX4I1 in Genome Data Viewer
    Location:
    16q24.1
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (85799695..85807068)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (91865215..91872584)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (85833301..85840674)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene ER membrane protein complex subunit 8 Neighboring gene RNA, U1 small nuclear 103, pseudogene Neighboring gene uncharacterized LOC101928557 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:85832503-85833109 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7823 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7824 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7825 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr16:85841166-85841873 Neighboring gene iron-sulfur cluster assembly 1 homolog (S. cerevisiae) pseudogene Neighboring gene ribosomal protein L10a pseudogene 12

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Mitochondrial complex 4 deficiency, nuclear type 16
    MedGen: C5436714 OMIM: 619060 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy.
    EBI GWAS Catalog
    Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans.
    EBI GWAS Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 is identified to have a physical interaction with cytochrome c oxidase subunit IV isoform 1 (COX4I1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    Envelope transmembrane glycoprotein gp41 env HIV-1 gp41 is identified to have a physical interaction with cytochrome c oxidase subunit IV isoform 1 (COX4I1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    Tat tat Tat-induced mitochondrial membrane permeabilization is associated with inhibition of cytochrome c oxidase (COX) activity by Tat in disrupted mitochondria from human samples PubMed
    Vpr vpr HIV-1 Vpr and FAT10 co-localize to mitochondria with marker protein Cox4 PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ23483, MGC72016

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cytochrome-c oxidase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cytosol IEA
    Inferred from Electronic Annotation
    more info
     
    located_in membrane HDA PubMed 
    located_in mitochondrial inner membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
     
    located_in mitochondrial membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of mitochondrial respiratory chain complex IV IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of mitochondrial respiratory chain complex IV IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    part_of mitochondrial respiratory chain complex IV IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    located_in mitochondrion HDA PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     

    General protein information

    Preferred Names
    cytochrome c oxidase subunit 4 isoform 1, mitochondrial
    Names
    cytochrome c oxidase polypeptide IV
    cytochrome c oxidase subunit IV
    NP_001305715.1
    NP_001305717.1
    NP_001305723.1
    NP_001305726.1
    NP_001305731.1
    NP_001852.1
    XP_024305924.1
    XP_047289579.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_042280.1 RefSeqGene

      Range
      5129..12502
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001318786.3NP_001305715.1  cytochrome c oxidase subunit 4 isoform 1, mitochondrial isoform 1 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AC018695, BC047869, BE615615, BE728651, BM835194, BU599266, U90915
      Consensus CDS
      CCDS10955.1
      UniProtKB/Swiss-Prot
      B2R4J2, D3DUM7, P13073, Q6P666
      Related
      ENSP00000457015.1, ENST00000561569.5
      Conserved Domains (1) summary
      pfam02936
      Location:36168
      COX4; Cytochrome c oxidase subunit IV
    2. NM_001318788.2NP_001305717.1  cytochrome c oxidase subunit 4 isoform 1, mitochondrial isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region, resulting in a frameshift and an early stop codon, compared to variant 1. It encodes isoform 2, which has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      BE615615, BP343428, BU599266, U90915
      UniProtKB/TrEMBL
      H3BN72
      Conserved Domains (1) summary
      cd00922
      Location:26126
      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. NM_001318794.2NP_001305723.1  cytochrome c oxidase subunit 4 isoform 1, mitochondrial isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate splice site in the 3' coding region, resulting in a different 3' coding region and 3' UTR, compared to variant 1. It encodes isoform 3, which has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC018695, BC062437, BE615615, BG614492, BM835194, BU599266, CN406213
      Consensus CDS
      CCDS82020.1
      UniProtKB/TrEMBL
      H3BN72, H3BNV9
      Related
      ENSP00000455030.1, ENST00000568794.5
      Conserved Domains (1) summary
      cd00922
      Location:26124
      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 ...
    4. NM_001318797.3NP_001305726.1  cytochrome c oxidase subunit 4 isoform 1, mitochondrial isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region and uses a downstream start codon, compared to variant 1. It encodes isoform 4, which is shorter at the N-terminus, compared to isoform 1.
      Source sequence(s)
      AC018695, BE615615, BE728651, BU599266, DB502762, U90915
      UniProtKB/TrEMBL
      H3BPG0
      Related
      ENSP00000455301.1, ENST00000566405.5
      Conserved Domains (1) summary
      pfam02936
      Location:1130
      COX4; Cytochrome c oxidase subunit IV
    5. NM_001318802.2NP_001305731.1  cytochrome c oxidase subunit 4 isoform 1, mitochondrial isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' and 3' UTRs and 5' and 3' coding regions, compared to variant 1. It encodes isoform 5, which is shorter and has distinct N- and C-termini, compared to isoform 1.
      Source sequence(s)
      BE615615, BM835194, BU599266, CD677397, U90915
      UniProtKB/Swiss-Prot
      P13073
      Conserved Domains (1) summary
      cl02792
      Location:2165
      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 ...
    6. NM_001861.6NP_001852.1  cytochrome c oxidase subunit 4 isoform 1, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_001852.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AC018695, BC062437, BE615615, BM835194, BU599266
      Consensus CDS
      CCDS10955.1
      UniProtKB/Swiss-Prot
      B2R4J2, D3DUM7, P13073, Q6P666
      Related
      ENSP00000253452.2, ENST00000253452.8
      Conserved Domains (1) summary
      pfam02936
      Location:36168
      COX4; Cytochrome c oxidase subunit IV

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      85799695..85807068
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024450156.2XP_024305924.1  cytochrome c oxidase subunit 4 isoform 1, mitochondrial isoform X1

      Conserved Domains (1) summary
      pfam02936
      Location:42174
      COX4; Cytochrome c oxidase subunit IV
    2. XM_047433623.1XP_047289579.1  cytochrome c oxidase subunit 4 isoform 1, mitochondrial isoform X2

      UniProtKB/Swiss-Prot
      B2R4J2, D3DUM7, P13073, Q6P666

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      91865215..91872584
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)