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Q16134 (ETFD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial

Short name=ETF-QO
Short name=ETF-ubiquinone oxidoreductase
EC=1.5.5.1
Alternative name(s):
Electron-transferring-flavoprotein dehydrogenase
Short name=ETF dehydrogenase
Gene names
Name:ETFDH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length617 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Accepts electrons from ETF and reduces ubiquinone.

Catalytic activity

Reduced electron-transferring flavoprotein + ubiquinone = electron-transferring flavoprotein + ubiquinol.

Cofactor

Binds 1 4Fe-4S cluster.

FAD.

Subunit structure

Monomer.

Subcellular location

Mitochondrion inner membrane.

Involvement in disease

Glutaric aciduria 2C (GA2C) [MIM:231680]: An autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the ETF-QO/FixC family.

Contains 1 4Fe-4S ferredoxin-type domain.

Sequence caution

The sequence CAD98030.1 differs from that shown. Reason: Aberrant splicing.

Ontologies

Keywords
   Biological processElectron transport
Transport
   Cellular componentMembrane
Mitochondrion
Mitochondrion inner membrane
   Coding sequence diversityPolymorphism
   DiseaseGlutaricaciduria
   DomainTransit peptide
   Ligand4Fe-4S
FAD
Flavoprotein
Iron
Iron-sulfur
Metal-binding
Ubiquinone
   Molecular functionOxidoreductase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular metabolic process

Traceable author statement. Source: Reactome

electron transport chain

Inferred from direct assay PubMed 12049629Ref.1. Source: UniProtKB

fatty acid beta-oxidation using acyl-CoA dehydrogenase

Inferred from mutant phenotype PubMed 17412732. Source: BHF-UCL

respiratory electron transport chain

Traceable author statement. Source: Reactome

response to oxidative stress

Inferred from sequence or structural similarity. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentintegral component of mitochondrial inner membrane

Inferred from direct assay Ref.1. Source: UniProtKB

mitochondrial matrix

Traceable author statement. Source: Reactome

mitochondrial membrane

Inferred from direct assay PubMed 12049629. Source: UniProtKB

   Molecular_function4 iron, 4 sulfur cluster binding

Inferred from direct assay PubMed 18037314. Source: UniProtKB

electron carrier activity

Inferred from direct assay PubMed 12049629Ref.1. Source: UniProtKB

electron-transferring-flavoprotein dehydrogenase activity

Inferred from direct assay PubMed 12049629PubMed 14640977Ref.1. Source: UniProtKB

flavin adenine dinucleotide binding

Inferred from sequence or structural similarity PubMed 17050691. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

oxidoreductase activity

Inferred from direct assay PubMed 14640977. Source: UniProtKB

oxidoreductase activity, oxidizing metal ions with flavin as acceptor

Inferred from sequence or structural similarity. Source: UniProtKB

quinone binding

Inferred from direct assay PubMed 14640977. Source: UniProtKB

ubiquinone binding

Inferred from direct assay PubMed 14640977. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3333Mitochondrion Potential
Chain34 – 617584Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial
PRO_0000008661

Regions

Intramembrane109 – 13022 By similarity
Intramembrane428 – 44720 By similarity
Domain577 – 606304Fe-4S ferredoxin-type
Nucleotide binding71 – 8515FAD Potential

Sites

Metal binding5611Iron-sulfur (4Fe-4S) Potential
Metal binding5861Iron-sulfur (4Fe-4S) Potential
Metal binding5891Iron-sulfur (4Fe-4S) Potential
Metal binding5921Iron-sulfur (4Fe-4S) Potential
Binding site3051Ubiquinone; via carbonyl oxygen By similarity
Binding site3061Ubiquinone; via amide nitrogen By similarity

Amino acid modifications

Modified residue961N6-acetyllysine By similarity
Modified residue1321N6-acetyllysine By similarity
Modified residue2231N6-acetyllysine By similarity
Modified residue3571N6-acetyllysine By similarity
Modified residue5511Phosphoserine By similarity

Natural variations

Natural variant311T → I. Ref.1 Ref.2 Ref.4
Corresponds to variant rs11559290 [ dbSNP | Ensembl ].
VAR_062966
Natural variant941H → R.
Corresponds to variant rs1140065 [ dbSNP | Ensembl ].
VAR_055711
Natural variant5651V → L in a colorectal cancer sample; somatic mutation. Ref.6
VAR_036134

Experimental info

Sequence conflict1091I → V in CAD98030. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q16134 [UniParc].

Last modified March 23, 2010. Version 2.
Checksum: 099EBA36C59AF3D6

FASTA61768,495
        10         20         30         40         50         60 
MLVPLAKLSC LAYQCFHALK IKKNYLPLCA TRWSSTSTVP RITTHYTIYP RDKDKRWEGV 

        70         80         90        100        110        120 
NMERFAEEAD VVIVGAGPAG LSAAVRLKQL AVAHEKDIRV CLVEKAAQIG AHTLSGACLD 

       130        140        150        160        170        180 
PGAFKELFPD WKEKGAPLNT PVTEDRFGIL TEKYRIPVPI LPGLPMNNHG NYIVRLGHLV 

       190        200        210        220        230        240 
SWMGEQAEAL GVEVYPGYAA AEVLFHDDGS VKGIATNDVG IQKDGAPKAT FERGLELHAK 

       250        260        270        280        290        300 
VTIFAEGCHG HLAKQLYKKF DLRANCEPQT YGIGLKELWV IDEKNWKPGR VDHTVGWPLD 

       310        320        330        340        350        360 
RHTYGGSFLY HLNEGEPLVA LGLVVGLDYQ NPYLSPFREF QRWKHHPSIR PTLEGGKRIA 

       370        380        390        400        410        420 
YGARALNEGG FQSIPKLTFP GGLLIGCSPG FMNVPKIKGT HTAMKSGILA AESIFNQLTS 

       430        440        450        460        470        480 
ENLQSKTIGL HVTEYEDNLK NSWVWKELYS VRNIRPSCHG VLGVYGGMIY TGIFYWILRG 

       490        500        510        520        530        540 
MEPWTLKHKG SDFERLKPAK DCTPIEYPKP DGQISFDLLS SVALSGTNHE HDQPAHLTLR 

       550        560        570        580        590        600 
DDSIPVNRNL SIYDGPEQRF CPAGVYEFVP VEQGDGFRLQ INAQNCVHCK TCDIKDPSQN 

       610 
INWVVPEGGG GPAYNGM 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and expression of a cDNA encoding human electron transfer flavoprotein-ubiquinone oxidoreductase."
Goodman S.I., Axtell K.M., Bindoff L.A., Beard S.E., Gill R.E., Frerman F.E.
Eur. J. Biochem. 219:277-286(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-31.
Tissue: Fetal liver.
[2]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-31.
Tissue: Small intestine.
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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], VARIANT ILE-31.
Tissue: Lung.
[5]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-565.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S69232 mRNA. Translation: AAC60628.1.
BX538129 mRNA. Translation: CAD98030.1. Sequence problems.
AC107219 Genomic DNA. No translation available.
BC011890 mRNA. Translation: AAH11890.1.
PIRS41115.
RefSeqNP_004444.2. NM_004453.3.
UniGeneHs.155729.

3D structure databases

ProteinModelPortalQ16134.
SMRQ16134. Positions 39-617.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108411. 2 interactions.
IntActQ16134. 1 interaction.
STRING9606.ENSP00000303552.

PTM databases

PhosphoSiteQ16134.

Polymorphism databases

DMDM292495008.

Proteomic databases

PaxDbQ16134.
PRIDEQ16134.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000511912; ENSP00000426638; ENSG00000171503.
GeneID2110.
KEGGhsa:2110.
UCSCuc003iqb.3. human.

Organism-specific databases

CTD2110.
GeneCardsGC04P159593.
H-InvDBHIX0200647.
HGNCHGNC:3483. ETFDH.
HPAHPA041978.
MIM231675. gene.
231680. phenotype.
neXtProtNX_Q16134.
Orphanet26791. Glutaric acidemia type 2.
PharmGKBPA27899.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0644.
HOGENOMHOG000259450.
HOVERGENHBG005615.
InParanoidQ16134.
KOK00311.
OMAEKDIRVC.
OrthoDBEOG7WX07W.
PhylomeDBQ16134.
TreeFamTF105687.

Enzyme and pathway databases

BioCycMetaCyc:HS10326-MONOMER.
BRENDA1.5.5.1. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ16134.
BgeeQ16134.
CleanExHS_ETFDH.
GenevestigatorQ16134.

Family and domain databases

InterProIPR017896. 4Fe4S_Fe-S-bd.
IPR007859. ETFD_OxRdtase.
IPR000103. Pyridine_nuc-diS_OxRdtase_2.
[Graphical view]
PfamPF05187. ETF_QO. 1 hit.
[Graphical view]
PRINTSPR00469. PNDRDTASEII.
PROSITEPS51379. 4FE4S_FER_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSETFDH. human.
GeneWikiETFDH.
GenomeRNAi2110.
NextBio8533.
PROQ16134.
SOURCESearch...

Entry information

Entry nameETFD_HUMAN
AccessionPrimary (citable) accession number: Q16134
Secondary accession number(s): Q7Z347
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 23, 2010
Last modified: April 16, 2014
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM