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Protein

Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial

Gene

ETFDH

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

Functioni

Accepts electrons from ETF and reduces ubiquinone.

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei305Ubiquinone; via carbonyl oxygenBy similarity1
Binding sitei306Ubiquinone; via amide nitrogenBy similarity1
Metal bindingi561Iron-sulfur (4Fe-4S)Sequence analysis1
Metal bindingi586Iron-sulfur (4Fe-4S)Sequence analysis1
Metal bindingi589Iron-sulfur (4Fe-4S)Sequence analysis1
Metal bindingi592Iron-sulfur (4Fe-4S)Sequence analysis1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi71 – 85FADSequence analysisAdd BLAST15

GO - Molecular functioni

  • 4 iron, 4 sulfur cluster binding Source: UniProtKB
  • electron carrier activity Source: UniProtKB
  • electron-transferring-flavoprotein dehydrogenase activity Source: UniProtKB
  • flavin adenine dinucleotide binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • oxidoreductase activity Source: UniProtKB
  • oxidoreductase activity, oxidizing metal ions with flavin as acceptor Source: UniProtKB
  • quinone binding Source: UniProtKB
  • ubiquinone binding Source: UniProtKB

GO - Biological processi

  • electron transport chain Source: UniProtKB
  • fatty acid beta-oxidation using acyl-CoA dehydrogenase Source: BHF-UCL
  • respiratory electron transport chain Source: GO_Central
  • response to oxidative stress Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Electron transport, Transport

Keywords - Ligandi

4Fe-4S, FAD, Flavoprotein, Iron, Iron-sulfur, Metal-binding, Ubiquinone

Enzyme and pathway databases

BioCyciMetaCyc:HS10326-MONOMER.
ZFISH:HS10326-MONOMER.
BRENDAi1.5.5.1. 2681.
ReactomeiR-HSA-611105. Respiratory electron transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial (EC:1.5.5.1)
Short name:
ETF-QO
Short name:
ETF-ubiquinone oxidoreductase
Alternative name(s):
Electron-transferring-flavoprotein dehydrogenase
Short name:
ETF dehydrogenase
Gene namesi
Name:ETFDH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:3483. ETFDH.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Intramembranei109 – 130By similarityAdd BLAST22
Intramembranei428 – 447By similarityAdd BLAST20

GO - Cellular componenti

  • integral component of mitochondrial inner membrane Source: UniProtKB
  • mitochondrial electron transfer flavoprotein complex Source: GO_Central
  • mitochondrial matrix Source: Reactome
  • mitochondrial membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Involvement in diseasei

Glutaric aciduria 2C (GA2C)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:231680
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07543949Y → C in GA2C; unknown pathological significance. 1 Publication1
Natural variantiVAR_07544082S → F in GA2C. 1 Publication1
Natural variantiVAR_07544182S → P in GA2C. 1 Publication1
Natural variantiVAR_07544284A → T in GA2C. 2 PublicationsCorresponds to variant rs121964954dbSNPEnsembl.1
Natural variantiVAR_075443112H → Y in GA2C. 1 Publication1
Natural variantiVAR_075444127L → H in GA2C. 1 PublicationCorresponds to variant rs121964956dbSNPEnsembl.1
Natural variantiVAR_075445138L → R in GA2C; unknown pathological significance. 1 PublicationCorresponds to variant rs779896449dbSNPEnsembl.1
Natural variantiVAR_075446175R → H in GA2C. 1 PublicationCorresponds to variant rs121964955dbSNPEnsembl.1
Natural variantiVAR_075447175R → L in GA2C. 1 PublicationCorresponds to variant rs121964955dbSNPEnsembl.1
Natural variantiVAR_075448218D → N in GA2C; unknown pathological significance. 1 PublicationCorresponds to variant rs748289922dbSNPEnsembl.1
Natural variantiVAR_075449222Q → P in GA2C; unknown pathological significance. 1 Publication1
Natural variantiVAR_075450262L → F in GA2C; unknown pathological significance. 1 Publication1
Natural variantiVAR_075451334L → P in GA2C; unknown pathological significance. 1 PublicationCorresponds to variant rs377686388dbSNPEnsembl.1
Natural variantiVAR_075452346H → R in GA2C; unknown pathological significance. 1 Publication1
Natural variantiVAR_075453377L → P in GA2C; unknown pathological significance. 1 PublicationCorresponds to variant rs387907170dbSNPEnsembl.1
Natural variantiVAR_075454452R → K in GA2C; unknown pathological significance. 1 Publication1
Natural variantiVAR_075455456P → L in GA2C. 2 PublicationsCorresponds to variant rs398124152dbSNPEnsembl.1
Natural variantiVAR_075456456P → T in GA2C. 1 Publication1
Natural variantiVAR_075457483P → L in GA2C; unknown pathological significance. 1 PublicationCorresponds to variant rs377656387dbSNPEnsembl.1
Natural variantiVAR_075458562P → L in GA2C. 1 Publication1
Natural variantiVAR_075459590K → E in GA2C. 1 Publication1
Natural variantiVAR_075460611G → E in GA2C. 1 PublicationCorresponds to variant rs761669036dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Glutaricaciduria

Organism-specific databases

DisGeNETi2110.
MalaCardsiETFDH.
MIMi231680. phenotype.
OpenTargetsiENSG00000171503.
Orphaneti394532. Multiple acyl-CoA dehydrogenation deficiency, mild type.
394529. Multiple acyl-CoA dehydrogenation deficiency, severe neonatal type.
PharmGKBiPA27899.

Polymorphism and mutation databases

BioMutaiETFDH.
DMDMi292495008.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 33MitochondrionSequence analysisAdd BLAST33
ChainiPRO_000000866134 – 617Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrialAdd BLAST584

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei96N6-acetyllysineBy similarity1
Modified residuei132N6-acetyllysineBy similarity1
Modified residuei223N6-acetyllysineBy similarity1
Modified residuei357N6-acetyllysineBy similarity1
Modified residuei551PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ16134.
MaxQBiQ16134.
PaxDbiQ16134.
PeptideAtlasiQ16134.
PRIDEiQ16134.

PTM databases

iPTMnetiQ16134.
PhosphoSitePlusiQ16134.
SwissPalmiQ16134.

Expressioni

Gene expression databases

BgeeiENSG00000171503.
CleanExiHS_ETFDH.
ExpressionAtlasiQ16134. baseline and differential.
GenevisibleiQ16134. HS.

Organism-specific databases

HPAiHPA041978.

Interactioni

Subunit structurei

Monomer.

Protein-protein interaction databases

BioGridi108411. 4 interactors.
IntActiQ16134. 2 interactors.
STRINGi9606.ENSP00000426638.

Structurei

3D structure databases

ProteinModelPortaliQ16134.
SMRiQ16134.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini577 – 6064Fe-4S ferredoxin-typePROSITE-ProRule annotationAdd BLAST30

Sequence similaritiesi

Belongs to the ETF-QO/FixC family.Curated
Contains 1 4Fe-4S ferredoxin-type domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2415. Eukaryota.
COG0644. LUCA.
GeneTreeiENSGT00390000010773.
HOGENOMiHOG000259450.
HOVERGENiHBG005615.
InParanoidiQ16134.
KOiK00311.
OMAiPKTTFER.
OrthoDBiEOG091G03C7.
PhylomeDBiQ16134.
TreeFamiTF105687.

Family and domain databases

Gene3Di3.50.50.60. 1 hit.
InterProiIPR017896. 4Fe4S_Fe-S-bd.
IPR007859. ETFD_OxRdtase/FixX.
IPR023753. FAD/NAD-binding_dom.
IPR000103. Pyridine_nuc-diS_OxRdtase_2.
[Graphical view]
PANTHERiPTHR10617:SF107. PTHR10617:SF107. 1 hit.
PfamiPF05187. ETF_QO. 1 hit.
[Graphical view]
PRINTSiPR00469. PNDRDTASEII.
SUPFAMiSSF51905. SSF51905. 2 hits.
PROSITEiPS51379. 4FE4S_FER_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q16134-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLVPLAKLSC LAYQCFHALK IKKNYLPLCA TRWSSTSTVP RITTHYTIYP
60 70 80 90 100
RDKDKRWEGV NMERFAEEAD VVIVGAGPAG LSAAVRLKQL AVAHEKDIRV
110 120 130 140 150
CLVEKAAQIG AHTLSGACLD PGAFKELFPD WKEKGAPLNT PVTEDRFGIL
160 170 180 190 200
TEKYRIPVPI LPGLPMNNHG NYIVRLGHLV SWMGEQAEAL GVEVYPGYAA
210 220 230 240 250
AEVLFHDDGS VKGIATNDVG IQKDGAPKAT FERGLELHAK VTIFAEGCHG
260 270 280 290 300
HLAKQLYKKF DLRANCEPQT YGIGLKELWV IDEKNWKPGR VDHTVGWPLD
310 320 330 340 350
RHTYGGSFLY HLNEGEPLVA LGLVVGLDYQ NPYLSPFREF QRWKHHPSIR
360 370 380 390 400
PTLEGGKRIA YGARALNEGG FQSIPKLTFP GGLLIGCSPG FMNVPKIKGT
410 420 430 440 450
HTAMKSGILA AESIFNQLTS ENLQSKTIGL HVTEYEDNLK NSWVWKELYS
460 470 480 490 500
VRNIRPSCHG VLGVYGGMIY TGIFYWILRG MEPWTLKHKG SDFERLKPAK
510 520 530 540 550
DCTPIEYPKP DGQISFDLLS SVALSGTNHE HDQPAHLTLR DDSIPVNRNL
560 570 580 590 600
SIYDGPEQRF CPAGVYEFVP VEQGDGFRLQ INAQNCVHCK TCDIKDPSQN
610
INWVVPEGGG GPAYNGM
Length:617
Mass (Da):68,495
Last modified:March 23, 2010 - v2
Checksum:i099EBA36C59AF3D6
GO
Isoform 2 (identifier: Q16134-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     12-58: Missing.

Note: No experimental confirmation available.
Show »
Length:570
Mass (Da):62,825
Checksum:i9F62F0271FA24BB0
GO

Sequence cautioni

The sequence CAD98030 differs from that shown. Aberrant splicing.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti109I → V in CAD98030 (PubMed:17974005).Curated1
Sequence conflicti456P → S in BAG65581 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07543816F → C.1 Publication1
Natural variantiVAR_06296631T → I.4 PublicationsCorresponds to variant rs11559290dbSNPEnsembl.1
Natural variantiVAR_07543949Y → C in GA2C; unknown pathological significance. 1 Publication1
Natural variantiVAR_07544082S → F in GA2C. 1 Publication1
Natural variantiVAR_07544182S → P in GA2C. 1 Publication1
Natural variantiVAR_07544284A → T in GA2C. 2 PublicationsCorresponds to variant rs121964954dbSNPEnsembl.1
Natural variantiVAR_05571194H → R.Corresponds to variant rs1140065dbSNPEnsembl.1
Natural variantiVAR_075443112H → Y in GA2C. 1 Publication1
Natural variantiVAR_075444127L → H in GA2C. 1 PublicationCorresponds to variant rs121964956dbSNPEnsembl.1
Natural variantiVAR_075445138L → R in GA2C; unknown pathological significance. 1 PublicationCorresponds to variant rs779896449dbSNPEnsembl.1
Natural variantiVAR_075446175R → H in GA2C. 1 PublicationCorresponds to variant rs121964955dbSNPEnsembl.1
Natural variantiVAR_075447175R → L in GA2C. 1 PublicationCorresponds to variant rs121964955dbSNPEnsembl.1
Natural variantiVAR_075448218D → N in GA2C; unknown pathological significance. 1 PublicationCorresponds to variant rs748289922dbSNPEnsembl.1
Natural variantiVAR_075449222Q → P in GA2C; unknown pathological significance. 1 Publication1
Natural variantiVAR_075450262L → F in GA2C; unknown pathological significance. 1 Publication1
Natural variantiVAR_075451334L → P in GA2C; unknown pathological significance. 1 PublicationCorresponds to variant rs377686388dbSNPEnsembl.1
Natural variantiVAR_075452346H → R in GA2C; unknown pathological significance. 1 Publication1
Natural variantiVAR_075453377L → P in GA2C; unknown pathological significance. 1 PublicationCorresponds to variant rs387907170dbSNPEnsembl.1
Natural variantiVAR_075454452R → K in GA2C; unknown pathological significance. 1 Publication1
Natural variantiVAR_075455456P → L in GA2C. 2 PublicationsCorresponds to variant rs398124152dbSNPEnsembl.1
Natural variantiVAR_075456456P → T in GA2C. 1 Publication1
Natural variantiVAR_075457483P → L in GA2C; unknown pathological significance. 1 PublicationCorresponds to variant rs377656387dbSNPEnsembl.1
Natural variantiVAR_075458562P → L in GA2C. 1 Publication1
Natural variantiVAR_036134565V → L in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs769893690dbSNPEnsembl.1
Natural variantiVAR_075459590K → E in GA2C. 1 Publication1
Natural variantiVAR_075460611G → E in GA2C. 1 PublicationCorresponds to variant rs761669036dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05515812 – 58Missing in isoform 2. 1 PublicationAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S69232 mRNA. Translation: AAC60628.1.
AK304838 mRNA. Translation: BAG65581.1.
BX538129 mRNA. Translation: CAD98030.1. Sequence problems.
AC107219 Genomic DNA. No translation available.
BC011890 mRNA. Translation: AAH11890.1.
CCDSiCCDS3800.1. [Q16134-1]
CCDS64090.1. [Q16134-3]
PIRiS41115.
RefSeqiNP_001268666.1. NM_001281737.1. [Q16134-3]
NP_004444.2. NM_004453.3. [Q16134-1]
UniGeneiHs.155729.

Genome annotation databases

EnsembliENST00000307738; ENSP00000303552; ENSG00000171503. [Q16134-3]
ENST00000511912; ENSP00000426638; ENSG00000171503. [Q16134-1]
GeneIDi2110.
KEGGihsa:2110.
UCSCiuc003iqb.5. human. [Q16134-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S69232 mRNA. Translation: AAC60628.1.
AK304838 mRNA. Translation: BAG65581.1.
BX538129 mRNA. Translation: CAD98030.1. Sequence problems.
AC107219 Genomic DNA. No translation available.
BC011890 mRNA. Translation: AAH11890.1.
CCDSiCCDS3800.1. [Q16134-1]
CCDS64090.1. [Q16134-3]
PIRiS41115.
RefSeqiNP_001268666.1. NM_001281737.1. [Q16134-3]
NP_004444.2. NM_004453.3. [Q16134-1]
UniGeneiHs.155729.

3D structure databases

ProteinModelPortaliQ16134.
SMRiQ16134.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108411. 4 interactors.
IntActiQ16134. 2 interactors.
STRINGi9606.ENSP00000426638.

PTM databases

iPTMnetiQ16134.
PhosphoSitePlusiQ16134.
SwissPalmiQ16134.

Polymorphism and mutation databases

BioMutaiETFDH.
DMDMi292495008.

Proteomic databases

EPDiQ16134.
MaxQBiQ16134.
PaxDbiQ16134.
PeptideAtlasiQ16134.
PRIDEiQ16134.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000307738; ENSP00000303552; ENSG00000171503. [Q16134-3]
ENST00000511912; ENSP00000426638; ENSG00000171503. [Q16134-1]
GeneIDi2110.
KEGGihsa:2110.
UCSCiuc003iqb.5. human. [Q16134-1]

Organism-specific databases

CTDi2110.
DisGeNETi2110.
GeneCardsiETFDH.
H-InvDBHIX0200647.
HGNCiHGNC:3483. ETFDH.
HPAiHPA041978.
MalaCardsiETFDH.
MIMi231675. gene.
231680. phenotype.
neXtProtiNX_Q16134.
OpenTargetsiENSG00000171503.
Orphaneti394532. Multiple acyl-CoA dehydrogenation deficiency, mild type.
394529. Multiple acyl-CoA dehydrogenation deficiency, severe neonatal type.
PharmGKBiPA27899.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2415. Eukaryota.
COG0644. LUCA.
GeneTreeiENSGT00390000010773.
HOGENOMiHOG000259450.
HOVERGENiHBG005615.
InParanoidiQ16134.
KOiK00311.
OMAiPKTTFER.
OrthoDBiEOG091G03C7.
PhylomeDBiQ16134.
TreeFamiTF105687.

Enzyme and pathway databases

BioCyciMetaCyc:HS10326-MONOMER.
ZFISH:HS10326-MONOMER.
BRENDAi1.5.5.1. 2681.
ReactomeiR-HSA-611105. Respiratory electron transport.

Miscellaneous databases

ChiTaRSiETFDH. human.
GeneWikiiETFDH.
GenomeRNAii2110.
PROiQ16134.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171503.
CleanExiHS_ETFDH.
ExpressionAtlasiQ16134. baseline and differential.
GenevisibleiQ16134. HS.

Family and domain databases

Gene3Di3.50.50.60. 1 hit.
InterProiIPR017896. 4Fe4S_Fe-S-bd.
IPR007859. ETFD_OxRdtase/FixX.
IPR023753. FAD/NAD-binding_dom.
IPR000103. Pyridine_nuc-diS_OxRdtase_2.
[Graphical view]
PANTHERiPTHR10617:SF107. PTHR10617:SF107. 1 hit.
PfamiPF05187. ETF_QO. 1 hit.
[Graphical view]
PRINTSiPR00469. PNDRDTASEII.
SUPFAMiSSF51905. SSF51905. 2 hits.
PROSITEiPS51379. 4FE4S_FER_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiETFD_HUMAN
AccessioniPrimary (citable) accession number: Q16134
Secondary accession number(s): B4E3R9, J3KND9, Q7Z347
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 23, 2010
Last modified: November 30, 2016
This is version 162 of the entry and version 2 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.