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Protein

Cytochrome c oxidase subunit NDUFA4

Gene

NDUFA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cytochrome c oxidase (COX, complex IV) is the terminal component of the mitochondrial respiratory chain that catalyzes the reduction of oxygen to water. Required for complex IV maintenance.1 Publication

GO - Molecular functioni

  • NADH dehydrogenase (ubiquinone) activity Source: UniProtKB
  • protein complex binding Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Electron transport, Respiratory chain, Transport

Enzyme and pathway databases

ReactomeiR-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-611105. Respiratory electron transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome c oxidase subunit NDUFA4
Alternative name(s):
Complex I-MLRQ
Short name:
CI-MLRQ
NADH-ubiquinone oxidoreductase MLRQ subunit
Gene namesi
Name:NDUFA4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:7687. NDUFA4.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • mitochondrial inner membrane Source: Reactome
  • mitochondrial respiratory chain complex I Source: UniProtKB
  • mitochondrial respiratory chain complex IV Source: UniProtKB
  • mitochondrion Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Involvement in diseasei

Leigh syndrome (LS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia.
See also OMIM:256000

Keywords - Diseasei

Leigh syndrome

Organism-specific databases

MalaCardsiNDUFA4.
MIMi256000. phenotype.
Orphaneti254905. Isolated cytochrome C oxidase deficiency.
PharmGKBiPA31493.

Chemistry

ChEMBLiCHEMBL2363065.

Polymorphism and mutation databases

BioMutaiNDUFA4.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 8181Cytochrome c oxidase subunit NDUFA4PRO_0000118821Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei10 – 101N6-acetyllysineBy similarity
Modified residuei66 – 661PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO00483.
MaxQBiO00483.
PaxDbiO00483.
PeptideAtlasiO00483.
PRIDEiO00483.
TopDownProteomicsiO00483.

PTM databases

iPTMnetiO00483.
PhosphoSiteiO00483.
SwissPalmiO00483.

Expressioni

Gene expression databases

BgeeiO00483.
CleanExiHS_NDUFA4.
ExpressionAtlasiO00483. baseline and differential.
GenevisibleiO00483. HS.

Organism-specific databases

HPAiHPA055323.

Interactioni

Subunit structurei

Component of the cytochrome c oxidase complex (COX, complex IV).1 Publication

GO - Molecular functioni

  • protein complex binding Source: MGI

Protein-protein interaction databases

BioGridi110777. 14 interactions.
IntActiO00483. 19 interactions.
STRINGi9606.ENSP00000339720.

Chemistry

BindingDBiO00483.

Structurei

3D structure databases

ProteinModelPortaliO00483.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the complex IV NDUFA4 subunit family.Curated

Phylogenomic databases

eggNOGiENOG410J0TX. Eukaryota.
ENOG41124SW. LUCA.
GeneTreeiENSGT00390000010457.
HOGENOMiHOG000261679.
HOVERGENiHBG006548.
InParanoidiO00483.
KOiK03948.
OMAiYKFYAVN.
OrthoDBiEOG71P2DD.
PhylomeDBiO00483.
TreeFamiTF106383.

Family and domain databases

InterProiIPR010530. B12D.
[Graphical view]
PANTHERiPTHR14256. PTHR14256. 1 hit.
PfamiPF06522. B12D. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O00483-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLRQIIGQAK KHPSLIPLFV FIGTGATGAT LYLLRLALFN PDVCWDRNNP
60 70 80
EPWNKLGPND QYKFYSVNVD YSKLKKERPD F
Length:81
Mass (Da):9,370
Last modified:July 1, 1997 - v1
Checksum:i2FA1D1115EDE24C7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U94586 mRNA. Translation: AAB52726.1.
AF201077 mRNA. Translation: AAF09253.1.
CR407618 mRNA. Translation: CAG28546.1.
CR541716 mRNA. Translation: CAG46517.1.
CH236948 Genomic DNA. Translation: EAL24297.1.
CH471073 Genomic DNA. Translation: EAW93631.1.
BC105295 mRNA. Translation: AAI05296.1.
BC101794 mRNA. Translation: AAI01795.1.
BC101796 mRNA. Translation: AAI01797.1.
CCDSiCCDS5357.1.
RefSeqiNP_002480.1. NM_002489.3.
UniGeneiHs.50098.

Genome annotation databases

EnsembliENST00000339600; ENSP00000339720; ENSG00000189043.
GeneIDi4697.
KEGGihsa:4697.
UCSCiuc003srx.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U94586 mRNA. Translation: AAB52726.1.
AF201077 mRNA. Translation: AAF09253.1.
CR407618 mRNA. Translation: CAG28546.1.
CR541716 mRNA. Translation: CAG46517.1.
CH236948 Genomic DNA. Translation: EAL24297.1.
CH471073 Genomic DNA. Translation: EAW93631.1.
BC105295 mRNA. Translation: AAI05296.1.
BC101794 mRNA. Translation: AAI01795.1.
BC101796 mRNA. Translation: AAI01797.1.
CCDSiCCDS5357.1.
RefSeqiNP_002480.1. NM_002489.3.
UniGeneiHs.50098.

3D structure databases

ProteinModelPortaliO00483.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110777. 14 interactions.
IntActiO00483. 19 interactions.
STRINGi9606.ENSP00000339720.

Chemistry

BindingDBiO00483.
ChEMBLiCHEMBL2363065.

PTM databases

iPTMnetiO00483.
PhosphoSiteiO00483.
SwissPalmiO00483.

Polymorphism and mutation databases

BioMutaiNDUFA4.

Proteomic databases

EPDiO00483.
MaxQBiO00483.
PaxDbiO00483.
PeptideAtlasiO00483.
PRIDEiO00483.
TopDownProteomicsiO00483.

Protocols and materials databases

DNASUi4697.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000339600; ENSP00000339720; ENSG00000189043.
GeneIDi4697.
KEGGihsa:4697.
UCSCiuc003srx.3. human.

Organism-specific databases

CTDi4697.
GeneCardsiNDUFA4.
HGNCiHGNC:7687. NDUFA4.
HPAiHPA055323.
MalaCardsiNDUFA4.
MIMi256000. phenotype.
603833. gene.
neXtProtiNX_O00483.
Orphaneti254905. Isolated cytochrome C oxidase deficiency.
PharmGKBiPA31493.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J0TX. Eukaryota.
ENOG41124SW. LUCA.
GeneTreeiENSGT00390000010457.
HOGENOMiHOG000261679.
HOVERGENiHBG006548.
InParanoidiO00483.
KOiK03948.
OMAiYKFYAVN.
OrthoDBiEOG71P2DD.
PhylomeDBiO00483.
TreeFamiTF106383.

Enzyme and pathway databases

ReactomeiR-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-611105. Respiratory electron transport.

Miscellaneous databases

ChiTaRSiNDUFA4. human.
GenomeRNAii4697.
NextBioi18114.
PROiO00483.
SOURCEiSearch...

Gene expression databases

BgeeiO00483.
CleanExiHS_NDUFA4.
ExpressionAtlasiO00483. baseline and differential.
GenevisibleiO00483. HS.

Family and domain databases

InterProiIPR010530. B12D.
[Graphical view]
PANTHERiPTHR14256. PTHR14256. 1 hit.
PfamiPF06522. B12D. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of the human cDNA sequence encoding the NADH:ubiquinone oxidoreductase MLRQ subunit."
    Kim J.W., Lee Y., Kang H.B., Chose Y.K., Chung T.W., Chang S.Y., Lee K.S., Choe I.S.
    Biochem. Mol. Biol. Int. 43:669-675(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.
  2. "Genomic sequence, cDNA sequence and chromosomal localization of the NDUFA4 human gene coding for the MLRQ subunit of NADH:ubiquinone oxidoreductase and its pseudogene."
    Kanagarajah D., Raha S., Scherer S., Robinson B.H.
    Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  5. "Human chromosome 7: DNA sequence and biology."
    Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
    , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
    Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  8. "The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification."
    Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., Ghosh S.S., Capaldi R.A.
    J. Biol. Chem. 278:13619-13622(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INITIAL IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. "NDUFA4 is a subunit of complex IV of the mammalian electron transport chain."
    Balsa E., Marco R., Perales-Clemente E., Szklarczyk R., Calvo E., Landazuri M.O., Enriquez J.A.
    Cell Metab. 16:378-386(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, IDENTFICATION AS CYTOCHROME C OXIDASE SUBUNIT.
  11. Cited for: SUBUNIT, SUBCELLULAR LOCATION, INVOLVEMENT IN LS.
  12. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiNDUA4_HUMAN
AccessioniPrimary (citable) accession number: O00483
Secondary accession number(s): A4D109, Q6FHN5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: May 11, 2016
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Miscellaneous

During complex IV purifications dissociates from complex IV upon treatment with standard detergent DDM (decyl beta-D-maltoside) in high concentrations (PubMed:22902835, PubMed:23746447).2 Publications

Caution

Was initially believed to be a subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I).1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.