UniProtKB - P12074 (CX6A1_HUMAN)
Cytochrome c oxidase subunit 6A1, mitochondrial
COX6A1
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 unsing 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: InterPro
- enzyme regulator activity Source: GO_Central
GO - Biological processi
- cellular respiration Source: ComplexPortal
- generation of precursor metabolites and energy Source: ProtInc
- mitochondrial electron transport, cytochrome c to oxygen Source: GO_Central
Keywordsi
Molecular function | Oxidoreductase |
Enzyme and pathway databases
PathwayCommonsi | P12074 |
Reactomei | R-HSA-5628897, TP53 Regulates Metabolic Genes R-HSA-611105, Respiratory electron transport R-HSA-9707564, Cytoprotection by HMOX1 |
SignaLinki | P12074 |
SIGNORi | P12074 |
UniPathwayi | UPA00705 |
Names & Taxonomyi
Protein namesi | Recommended name: Cytochrome c oxidase subunit 6A1, mitochondrialAlternative name(s): Cytochrome c oxidase polypeptide VIa-liver Cytochrome c oxidase subunit VIA-liver Short name: COX VIa-L |
Gene namesi | Name:COX6A1 Synonyms:COX6AL |
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:2277, COX6A1 |
MIMi | 602072, gene |
neXtProti | NX_P12074 |
VEuPathDBi | HostDB:ENSG00000111775 |
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane 1 Publication; Single-pass membrane protein 1 Publication
Mitochondrion
- mitochondrial inner membrane Source: Reactome
- mitochondrial membrane Source: ComplexPortal
- mitochondrial respiratory chain complex IV Source: ComplexPortal
- mitochondrion Source: HPA
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 25 – 34 | Mitochondrial matrix1 Publication | 10 | |
Transmembranei | 35 – 59 | HelicalBy similarityAdd BLAST | 25 | |
Topological domaini | 60 – 109 | Mitochondrial intermembrane1 PublicationAdd BLAST | 50 |
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Involvement in diseasei
Charcot-Marie-Tooth disease, recessive, intermediate type, D (CMTRID)1 Publication
Keywords - Diseasei
Charcot-Marie-Tooth disease, Neurodegeneration, NeuropathyOrganism-specific databases
DisGeNETi | 1337 |
MalaCardsi | COX6A1 |
MIMi | 616039, phenotype |
OpenTargetsi | ENSG00000111775 |
Orphaneti | 435998, Autosomal recessive intermediate Charcot-Marie-Tooth disease type D |
PharmGKBi | PA26794 |
Miscellaneous databases
Pharosi | P12074, Tbio |
Genetic variation databases
BioMutai | COX6A1 |
DMDMi | 6166030 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 24 | Mitochondrion1 PublicationAdd BLAST | 24 | |
ChainiPRO_0000006119 | 25 – 109 | Cytochrome c oxidase subunit 6A1, mitochondrialAdd BLAST | 85 |
Proteomic databases
EPDi | P12074 |
jPOSTi | P12074 |
MassIVEi | P12074 |
MaxQBi | P12074 |
PaxDbi | P12074 |
PeptideAtlasi | P12074 |
PRIDEi | P12074 |
ProteomicsDBi | 52823 |
TopDownProteomicsi | P12074 |
2D gel databases
SWISS-2DPAGEi | P12074 |
PTM databases
iPTMneti | P12074 |
PhosphoSitePlusi | P12074 |
Expressioni
Gene expression databases
Bgeei | ENSG00000111775, Expressed in prefrontal cortex and 118 other tissues |
ExpressionAtlasi | P12074, baseline and differential |
Genevisiblei | P12074, HS |
Organism-specific databases
HPAi | ENSG00000111775, Low tissue specificity |
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 (PubMed:30030519). 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) (PubMed:28844695).
2 PublicationsBinary interactionsi
Protein-protein interaction databases
BioGRIDi | 107730, 51 interactors |
ComplexPortali | CPX-6123, Mitochondrial respiratory chain complex IV |
IntActi | P12074, 17 interactors |
STRINGi | 9606.ENSP00000229379 |
Miscellaneous databases
RNActi | P12074, protein |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transit peptide, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3469, Eukaryota |
GeneTreei | ENSGT00940000154612 |
HOGENOMi | CLU_122515_1_1_1 |
InParanoidi | P12074 |
OMAi | GYEGHDE |
OrthoDBi | 1591077at2759 |
PhylomeDBi | P12074 |
TreeFami | TF105064 |
Family and domain databases
CDDi | cd00925, Cyt_c_Oxidase_VIa, 1 hit |
Gene3Di | 4.10.95.10, 1 hit |
InterProi | View protein in InterPro IPR001349, Cyt_c_oxidase_su6a IPR018507, Cyt_c_oxidase_su6a_CS IPR036418, Cyt_c_oxidase_su6a_sf |
PANTHERi | PTHR11504, PTHR11504, 1 hit |
Pfami | View protein in Pfam PF02046, COX6A, 1 hit |
PIRSFi | PIRSF000277, COX6A1, 1 hit |
SUPFAMi | SSF81411, SSF81411, 1 hit |
PROSITEi | View protein in PROSITE PS01329, COX6A, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MAVVGVSSVS RLLGRSRPQL GRPMSSGAHG EEGSARMWKT LTFFVALPGV
60 70 80 90 100
AVSMLNVYLK SHHGEHERPE FIAYPHLRIR TKPFPWGDGN HTLFHNPHVN
PLPTGYEDE
Sequence cautioni
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK312009 mRNA Translation: BAG34947.1 AL021546 Genomic DNA No translation available. BC007723 mRNA Translation: AAH07723.1 BC070186 mRNA Translation: AAH70186.1 BC107861 mRNA Translation: AAI07862.1 X15341 mRNA Translation: CAA33392.1 Frameshift. |
CCDSi | CCDS9197.1 |
RefSeqi | NP_004364.2, NM_004373.3 |
Genome annotation databases
Ensembli | ENST00000229379.3; ENSP00000229379.2; ENSG00000111775.3 |
GeneIDi | 1337 |
KEGGi | hsa:1337 |
MANE-Selecti | ENST00000229379.3; ENSP00000229379.2; NM_004373.4; NP_004364.2 |
UCSCi | uc001tyf.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK312009 mRNA Translation: BAG34947.1 AL021546 Genomic DNA No translation available. BC007723 mRNA Translation: AAH07723.1 BC070186 mRNA Translation: AAH70186.1 BC107861 mRNA Translation: AAI07862.1 X15341 mRNA Translation: CAA33392.1 Frameshift. |
CCDSi | CCDS9197.1 |
RefSeqi | NP_004364.2, NM_004373.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5Z62 | electron microscopy | 3.60 | G | 34-108 | [»] | |
AlphaFoldDBi | P12074 | |||||
SMRi | P12074 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107730, 51 interactors |
ComplexPortali | CPX-6123, Mitochondrial respiratory chain complex IV |
IntActi | P12074, 17 interactors |
STRINGi | 9606.ENSP00000229379 |
PTM databases
iPTMneti | P12074 |
PhosphoSitePlusi | P12074 |
Genetic variation databases
BioMutai | COX6A1 |
DMDMi | 6166030 |
2D gel databases
SWISS-2DPAGEi | P12074 |
Proteomic databases
EPDi | P12074 |
jPOSTi | P12074 |
MassIVEi | P12074 |
MaxQBi | P12074 |
PaxDbi | P12074 |
PeptideAtlasi | P12074 |
PRIDEi | P12074 |
ProteomicsDBi | 52823 |
TopDownProteomicsi | P12074 |
Protocols and materials databases
Antibodypediai | 45523, 347 antibodies from 29 providers |
DNASUi | 1337 |
Genome annotation databases
Ensembli | ENST00000229379.3; ENSP00000229379.2; ENSG00000111775.3 |
GeneIDi | 1337 |
KEGGi | hsa:1337 |
MANE-Selecti | ENST00000229379.3; ENSP00000229379.2; NM_004373.4; NP_004364.2 |
UCSCi | uc001tyf.2, human |
Organism-specific databases
CTDi | 1337 |
DisGeNETi | 1337 |
GeneCardsi | COX6A1 |
HGNCi | HGNC:2277, COX6A1 |
HPAi | ENSG00000111775, Low tissue specificity |
MalaCardsi | COX6A1 |
MIMi | 602072, gene 616039, phenotype |
neXtProti | NX_P12074 |
OpenTargetsi | ENSG00000111775 |
Orphaneti | 435998, Autosomal recessive intermediate Charcot-Marie-Tooth disease type D |
PharmGKBi | PA26794 |
VEuPathDBi | HostDB:ENSG00000111775 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3469, Eukaryota |
GeneTreei | ENSGT00940000154612 |
HOGENOMi | CLU_122515_1_1_1 |
InParanoidi | P12074 |
OMAi | GYEGHDE |
OrthoDBi | 1591077at2759 |
PhylomeDBi | P12074 |
TreeFami | TF105064 |
Enzyme and pathway databases
UniPathwayi | UPA00705 |
PathwayCommonsi | P12074 |
Reactomei | R-HSA-5628897, TP53 Regulates Metabolic Genes R-HSA-611105, Respiratory electron transport R-HSA-9707564, Cytoprotection by HMOX1 |
SignaLinki | P12074 |
SIGNORi | P12074 |
Miscellaneous databases
BioGRID-ORCSi | 1337, 119 hits in 1039 CRISPR screens |
ChiTaRSi | COX6A1, human |
GeneWikii | COX6A1 |
GenomeRNAii | 1337 |
Pharosi | P12074, Tbio |
PROi | PR:P12074 |
RNActi | P12074, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000111775, Expressed in prefrontal cortex and 118 other tissues |
ExpressionAtlasi | P12074, baseline and differential |
Genevisiblei | P12074, HS |
Family and domain databases
CDDi | cd00925, Cyt_c_Oxidase_VIa, 1 hit |
Gene3Di | 4.10.95.10, 1 hit |
InterProi | View protein in InterPro IPR001349, Cyt_c_oxidase_su6a IPR018507, Cyt_c_oxidase_su6a_CS IPR036418, Cyt_c_oxidase_su6a_sf |
PANTHERi | PTHR11504, PTHR11504, 1 hit |
Pfami | View protein in Pfam PF02046, COX6A, 1 hit |
PIRSFi | PIRSF000277, COX6A1, 1 hit |
SUPFAMi | SSF81411, SSF81411, 1 hit |
PROSITEi | View protein in PROSITE PS01329, COX6A, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CX6A1_HUMAN | |
Accessioni | P12074Primary (citable) accession number: P12074 Secondary accession number(s): B2R500, O43714, Q32Q37 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1989 |
Last sequence update: | July 15, 1999 | |
Last modified: | May 25, 2022 | |
This is version 197 of the entry and version 4 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
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families