UniProtKB - Q96KJ9 (COX42_HUMAN)
Cytochrome c oxidase subunit 4 isoform 2, mitochondrial
COX4I2
Functioni
Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
By similarity: oxidative phosphorylation Pathwayi
This protein is involved in the pathway oxidative phosphorylation, which is part of Energy metabolism.By similarityView all proteins of this organism that are known to be involved in the pathway oxidative phosphorylation and in Energy metabolism.
GO - Molecular functioni
- cytochrome-c oxidase activity Source: UniProtKB
GO - Biological processi
- cellular respiration Source: UniProtKB
- generation of precursor metabolites and energy Source: UniProtKB
- mitochondrial electron transport, cytochrome c to oxygen Source: UniProtKB
Enzyme and pathway databases
PathwayCommonsi | Q96KJ9 |
SignaLinki | Q96KJ9 |
UniPathwayi | UPA00705 |
Protein family/group databases
TCDBi | 3.D.4.11.1, the proton-translocating cytochrome oxidase (cox) superfamily |
Names & Taxonomyi
Protein namesi | Recommended name: Cytochrome c oxidase subunit 4 isoform 2, mitochondrialAlternative name(s): Cytochrome c oxidase subunit IV isoform 2 Short name: COX IV-2 |
Gene namesi | Name:COX4I2 Synonyms:COX4L2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:16232, COX4I2 |
MIMi | 607976, gene |
neXtProti | NX_Q96KJ9 |
VEuPathDBi | HostDB:ENSG00000131055 |
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane By similarity; Single-pass membrane protein By similarity
Mitochondrion
- mitochondrial respiratory chain complex IV Source: GO_Central
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 29 – 100 | Mitochondrial matrixBy similarityAdd BLAST | 72 | |
Transmembranei | 101 – 126 | HelicalBy similarityAdd BLAST | 26 | |
Topological domaini | 127 – 171 | Mitochondrial intermembraneBy similarityAdd BLAST | 45 |
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Involvement in diseasei
Exocrine pancreatic insufficiency dyserythropoietic anemia and calvarial hyperostosis (EPIDACH)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_058101 | 138 | E → K in EPIDACH; expression in patient fibroblasts is reduced to 25% of control values in normoxic conditions; the mutant protein shows an impaired response to hypoxia. 1 PublicationCorresponds to variant dbSNP:rs119455950EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 84701 |
MalaCardsi | COX4I2 |
MIMi | 612714, phenotype |
OpenTargetsi | ENSG00000131055 |
Orphaneti | 199337, Pancreatic insufficiency-anemia-hyperostosis syndrome |
PharmGKBi | PA26783 |
Miscellaneous databases
Pharosi | Q96KJ9, Tbio |
Genetic variation databases
BioMutai | COX4I2 |
DMDMi | 73620953 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 28 | MitochondrionSequence analysisAdd BLAST | 28 | |
ChainiPRO_0000006089 | 29 – 171 | Cytochrome c oxidase subunit 4 isoform 2, mitochondrialAdd BLAST | 143 |
Proteomic databases
EPDi | Q96KJ9 |
jPOSTi | Q96KJ9 |
MassIVEi | Q96KJ9 |
PaxDbi | Q96KJ9 |
PeptideAtlasi | Q96KJ9 |
PRIDEi | Q96KJ9 |
ProteomicsDBi | 77079 |
PTM databases
PhosphoSitePlusi | Q96KJ9 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000131055, Expressed in placenta and 179 other tissues |
ExpressionAtlasi | Q96KJ9, baseline and differential |
Genevisiblei | Q96KJ9, HS |
Organism-specific databases
HPAi | ENSG00000131055, Tissue enhanced (lung, placenta) |
Interactioni
Subunit structurei
Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I1 (or COX4I2), COX5A, COX5B, COX6A1 (or COX6A2), COX6B1 (or COX6B2), COX6C, COX7A2 (or COX7A1), COX7B, COX7C, COX8A and NDUFA4, which are encoded in the nuclear genome (By similarity). The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI1III2IV1 and megacomplex MCI2III2IV2) (By similarity).
By similarityProtein-protein interaction databases
BioGRIDi | 124215, 26 interactors |
IntActi | Q96KJ9, 3 interactors |
STRINGi | 9606.ENSP00000365243 |
Miscellaneous databases
RNActi | Q96KJ9, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 13 – 32 | DisorderedSequence analysisAdd BLAST | 20 |
Sequence similaritiesi
Keywords - Domaini
Transit peptide, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4075, Eukaryota |
GeneTreei | ENSGT00390000002407 |
HOGENOMi | CLU_117340_1_1_1 |
InParanoidi | Q96KJ9 |
OMAi | MLSRATW |
OrthoDBi | 1591226at2759 |
PhylomeDBi | Q96KJ9 |
TreeFami | TF105061 |
Family and domain databases
CDDi | cd00922, Cyt_c_Oxidase_IV, 1 hit |
Gene3Di | 1.10.442.10, 1 hit |
InterProi | View protein in InterPro IPR013288, Cyt_c_oxidase_su4 IPR004203, Cyt_c_oxidase_su4_fam IPR036639, Cyt_c_oxidase_su4_sf |
PANTHERi | PTHR10707, PTHR10707, 1 hit |
Pfami | View protein in Pfam PF02936, COX4, 1 hit |
PRINTSi | PR01873, CYTCOXIDASE4 |
SUPFAMi | SSF81406, SSF81406, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MLPRAAWSLV LRKGGGGRRG MHSSEGTTRG GGKMSPYTNC YAQRYYPMPE
60 70 80 90 100
EPFCTELNAE EQALKEKEKG SWTQLTHAEK VALYRLQFNE TFAEMNRRSN
110 120 130 140 150
EWKTVMGCVF FFIGFAALVI WWQRVYVFPP KPITLTDERK AQQLQRMLDM
160 170
KVNPVQGLAS RWDYEKKQWK K
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_058101 | 138 | E → K in EPIDACH; expression in patient fibroblasts is reduced to 25% of control values in normoxic conditions; the mutant protein shows an impaired response to hypoxia. 1 PublicationCorresponds to variant dbSNP:rs119455950EnsemblClinVar. | 1 | |
Natural variantiVAR_033815 | 161 | R → H1 PublicationCorresponds to variant dbSNP:rs11907253EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF257180 mRNA Translation: AAK49333.1 AL117381 Genomic DNA No translation available. BC057779 mRNA Translation: AAH57779.1 |
CCDSi | CCDS13187.1 |
RefSeqi | NP_115998.2, NM_032609.2 |
Genome annotation databases
Ensembli | ENST00000376075.4; ENSP00000365243.3; ENSG00000131055.5 |
GeneIDi | 84701 |
KEGGi | hsa:84701 |
MANE-Selecti | ENST00000376075.4; ENSP00000365243.3; NM_032609.3; NP_115998.2 |
UCSCi | uc002wwj.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF257180 mRNA Translation: AAK49333.1 AL117381 Genomic DNA No translation available. BC057779 mRNA Translation: AAH57779.1 |
CCDSi | CCDS13187.1 |
RefSeqi | NP_115998.2, NM_032609.2 |
3D structure databases
AlphaFoldDBi | Q96KJ9 |
SMRi | Q96KJ9 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 124215, 26 interactors |
IntActi | Q96KJ9, 3 interactors |
STRINGi | 9606.ENSP00000365243 |
Protein family/group databases
TCDBi | 3.D.4.11.1, the proton-translocating cytochrome oxidase (cox) superfamily |
PTM databases
PhosphoSitePlusi | Q96KJ9 |
Genetic variation databases
BioMutai | COX4I2 |
DMDMi | 73620953 |
Proteomic databases
EPDi | Q96KJ9 |
jPOSTi | Q96KJ9 |
MassIVEi | Q96KJ9 |
PaxDbi | Q96KJ9 |
PeptideAtlasi | Q96KJ9 |
PRIDEi | Q96KJ9 |
ProteomicsDBi | 77079 |
Protocols and materials databases
Antibodypediai | 25206, 201 antibodies from 30 providers |
DNASUi | 84701 |
Genome annotation databases
Ensembli | ENST00000376075.4; ENSP00000365243.3; ENSG00000131055.5 |
GeneIDi | 84701 |
KEGGi | hsa:84701 |
MANE-Selecti | ENST00000376075.4; ENSP00000365243.3; NM_032609.3; NP_115998.2 |
UCSCi | uc002wwj.2, human |
Organism-specific databases
CTDi | 84701 |
DisGeNETi | 84701 |
GeneCardsi | COX4I2 |
HGNCi | HGNC:16232, COX4I2 |
HPAi | ENSG00000131055, Tissue enhanced (lung, placenta) |
MalaCardsi | COX4I2 |
MIMi | 607976, gene 612714, phenotype |
neXtProti | NX_Q96KJ9 |
OpenTargetsi | ENSG00000131055 |
Orphaneti | 199337, Pancreatic insufficiency-anemia-hyperostosis syndrome |
PharmGKBi | PA26783 |
VEuPathDBi | HostDB:ENSG00000131055 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4075, Eukaryota |
GeneTreei | ENSGT00390000002407 |
HOGENOMi | CLU_117340_1_1_1 |
InParanoidi | Q96KJ9 |
OMAi | MLSRATW |
OrthoDBi | 1591226at2759 |
PhylomeDBi | Q96KJ9 |
TreeFami | TF105061 |
Enzyme and pathway databases
UniPathwayi | UPA00705 |
PathwayCommonsi | Q96KJ9 |
SignaLinki | Q96KJ9 |
Miscellaneous databases
BioGRID-ORCSi | 84701, 24 hits in 1072 CRISPR screens |
GeneWikii | COX4I2 |
GenomeRNAii | 84701 |
Pharosi | Q96KJ9, Tbio |
PROi | PR:Q96KJ9 |
RNActi | Q96KJ9, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000131055, Expressed in placenta and 179 other tissues |
ExpressionAtlasi | Q96KJ9, baseline and differential |
Genevisiblei | Q96KJ9, HS |
Family and domain databases
CDDi | cd00922, Cyt_c_Oxidase_IV, 1 hit |
Gene3Di | 1.10.442.10, 1 hit |
InterProi | View protein in InterPro IPR013288, Cyt_c_oxidase_su4 IPR004203, Cyt_c_oxidase_su4_fam IPR036639, Cyt_c_oxidase_su4_sf |
PANTHERi | PTHR10707, PTHR10707, 1 hit |
Pfami | View protein in Pfam PF02936, COX4, 1 hit |
PRINTSi | PR01873, CYTCOXIDASE4 |
SUPFAMi | SSF81406, SSF81406, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | COX42_HUMAN | |
Accessioni | Q96KJ9Primary (citable) accession number: Q96KJ9 Secondary accession number(s): Q6GTF4, Q9H0Z4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 3, 2002 |
Last sequence update: | August 16, 2005 | |
Last modified: | May 25, 2022 | |
This is version 154 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 20
Human chromosome 20: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families