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

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: mouse all
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Genomic context

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_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Replicative Stress Coincides with Impaired Nuclear DNA Damage Response in COX4-1 Deficiency.
Title: Replicative Stress Coincides with Impaired Nuclear DNA Damage Response in COX4-1 Deficiency.
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.
In case of myocardial insufficiency and dilated cardiomyopathy, decreased expression of COX 4 results in an impaired CytOx activity. Higher enzymatic activity but equal oxygen consumption contribute to the pathophysiology of the myocardial insufficiency and appears as an indicator of oxidative stress. This kind of dysregulation should be in the focus for the development of diagnostic and therapy procedures
Title: Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidase.
COX4I1 variant K101N was identified in a patient with short stature, poor weight gain and increased chromosomal breaks, simulating Fanconi anemia.
Title: Mutation in the COX4I1 gene is associated with short stature, poor weight gain and increased chromosomal breaks, simulating Fanconi anemia.
This cohort study showed that the COX411 gene was down regulation between patients with idiopathic Parkinson disease and controls
Title: Analysis of blood-based gene expression in idiopathic Parkinson disease.
We provide evidence that COX4-1 controls BMI1 expression via a redox mechanism
Title: Nuclear-encoded cytochrome c oxidase subunit 4 regulates BMI1 expression and determines proliferative capacity of high-grade gliomas.
COXIV mRNA (1.6 fold; P<0.01) and COXIV protein expression (1.5 fold; P<0.05) were increased by training but COXIV protein expression was decreased (20%; P<0.01) by acute exercise pre- and post-training.
Title: Short-term intensified cycle training alters acute and chronic responses of PGC1α and Cytochrome C oxidase IV to exercise in human skeletal muscle.
COX activity (electron transport complex IV) is reduced by 29% in maternal history of Alzheimer's disease compared to normal controls, and by 30% compared to paternal history of Alzheimer's disease.
Title: Reduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer's disease.
Studies suggest a model that links cell signaling with the phosphorylation state of Cytochrome c (Cytc) and cytochrome c oxidase (COX).
Title: Regulation of mitochondrial respiration and apoptosis through cell signaling: cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation.
Studies suggest that the main function of nuclear encoded subunits of cytochrome c oxidase appears to be "only" to control the activity of the mitochondrial subunits.
Title: Cytochrome c oxidase: evolution of control via nuclear subunit addition.

Submit: New GeneRIF Correction See all GeneRIFs (18)

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
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 EBI GWAS CatalogPubMed
Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH66835 (e-PCR)
- UniSTS:4116

RH41774 (e-PCR)
- UniSTS:89637

D8S2279 (e-PCR)
- UniSTS:473907

D13S1553 (e-PCR)
- UniSTS:473482

D11S3114 (e-PCR)
- UniSTS:152207

PMC164701P1 (e-PCR)
- UniSTS:271513

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

Process	Evidence Code	Pubs
involved_in cellular respiration	NAS Non-traceable Author Statement more info	PubMed
involved_in generation of precursor metabolites and energy	TAS 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	NAS Non-traceable Author Statement more info	PubMed
involved_in proton transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	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 more info	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

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Preferred Names: cytochrome c oxidase subunit 4 isoform 1, mitochondrial

Names: cytochrome c oxidase polypeptide IV; cytochrome c oxidase subunit IV

NP_001305715.1

EC 7.1.1.9

NP_001305717.1

EC 7.1.1.9

NP_001305723.1

EC 7.1.1.9

NP_001305726.1

EC 7.1.1.9

NP_001305731.1

EC 7.1.1.9

NP_001852.1

EC 7.1.1.9

XP_024305924.1

EC 7.1.1.9

XP_047289579.1

EC 7.1.1.9

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

NG_042280.1 RefSeqGene

Range

5129..12502

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001318786.3 → NP_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:36 → 168

COX4; Cytochrome c oxidase subunit IV
NM_001318788.2 → NP_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:26 → 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 ...
NM_001318794.2 → NP_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:26 → 124

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 ...
NM_001318797.3 → NP_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:1 → 130

COX4; Cytochrome c oxidase subunit IV
NM_001318802.2 → NP_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:21 → 65

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 ...
NM_001861.6 → NP_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:36 → 168

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

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

85799695..85807068

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Conserved Domains (1) summary

pfam02936
Location:42 → 174

COX4; Cytochrome c oxidase subunit IV
XM_047433623.1 → XP_047289579.1 cytochrome c oxidase subunit 4 isoform 1, mitochondrial isoform X2

UniProtKB/Swiss-Prot

B2R4J2, D3DUM7, P13073, Q6P666