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Protein

Electron transfer flavoprotein subunit alpha, mitochondrial

Gene

ETFA

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

Functioni

The electron transfer flavoprotein serves as a specific electron acceptor for several dehydrogenases, including five acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase).

Cofactori

FAD1 PublicationNote: Binds 1 FAD per dimer.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi274 – 302FAD1 PublicationAdd BLAST29

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Electron transport, Transport

Keywords - Ligandi

FAD, Flavoprotein

Enzyme and pathway databases

BioCyciZFISH:ETFACLOS-MONOMER.
ReactomeiR-HSA-611105. Respiratory electron transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Electron transfer flavoprotein subunit alpha, mitochondrial
Short name:
Alpha-ETF
Gene namesi
Name:ETFA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:3481. ETFA.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Glutaric aciduria 2A (GA2A)2 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_002366116G → R in GA2A. 1 PublicationCorresponds to variant rs119458971dbSNPEnsembl.1
Natural variantiVAR_002367157V → G in GA2A. 1 PublicationCorresponds to variant rs119458969dbSNPEnsembl.1
Natural variantiVAR_002368266T → M in GA2A. 1 PublicationCorresponds to variant rs119458970dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Glutaricaciduria

Organism-specific databases

DisGeNETi2108.
MalaCardsiETFA.
MIMi231680. phenotype.
OpenTargetsiENSG00000140374.
Orphaneti394532. Multiple acyl-CoA dehydrogenation deficiency, mild type.
394529. Multiple acyl-CoA dehydrogenation deficiency, severe neonatal type.
PharmGKBiPA27897.

Polymorphism and mutation databases

BioMutaiETFA.
DMDMi119636.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 19MitochondrionSequence analysisCombined sourcesAdd BLAST19
ChainiPRO_000000865020 – 333Electron transfer flavoprotein subunit alpha, mitochondrialAdd BLAST314

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei59N6-acetyllysine; alternateBy similarity1
Modified residuei59N6-succinyllysine; alternateBy similarity1
Modified residuei62N6-acetyllysineBy similarity1
Modified residuei69N6-acetyllysine; alternateBy similarity1
Modified residuei69N6-succinyllysine; alternateBy similarity1
Modified residuei75N6-acetyllysineBy similarity1
Modified residuei85N6-acetyllysine; alternateBy similarity1
Modified residuei85N6-succinyllysine; alternateBy similarity1
Modified residuei93PhosphothreonineBy similarity1
Modified residuei101N6-acetyllysineBy similarity1
Modified residuei139N6-acetyllysineBy similarity1
Modified residuei140PhosphoserineCombined sources1
Modified residuei158N6-acetyllysine; alternateBy similarity1
Modified residuei158N6-succinyllysine; alternateBy similarity1
Modified residuei164N6-acetyllysineBy similarity1
Modified residuei187N6-succinyllysineBy similarity1
Modified residuei203N6-acetyllysine; alternateBy similarity1
Modified residuei203N6-succinyllysine; alternateBy similarity1
Modified residuei216N6-succinyllysineBy similarity1
Modified residuei226N6-acetyllysine; alternateBy similarity1
Modified residuei226N6-succinyllysine; alternateBy similarity1
Modified residuei232N6-acetyllysine; alternateBy similarity1
Modified residuei232N6-succinyllysine; alternateBy similarity1
Modified residuei301N6-succinyllysineBy similarity1

Post-translational modificationi

The N-terminus is blocked.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP13804.
PaxDbiP13804.
PeptideAtlasiP13804.
PRIDEiP13804.
TopDownProteomicsiP13804-1. [P13804-1]
P13804-2. [P13804-2]

2D gel databases

UCD-2DPAGEP13804.

PTM databases

iPTMnetiP13804.
PhosphoSitePlusiP13804.
SwissPalmiP13804.

Expressioni

Gene expression databases

BgeeiENSG00000140374.
CleanExiHS_ETFA.
ExpressionAtlasiP13804. baseline and differential.
GenevisibleiP13804. HS.

Organism-specific databases

HPAiHPA018990.
HPA018993.
HPA018996.
HPA024089.

Interactioni

Subunit structurei

Electron transfer flavoprotein is a heterodimer composed of ETFA and ETFB (PubMed:8962055). Interacts with ETFRF1 (PubMed:27499296).2 Publications

Protein-protein interaction databases

BioGridi108409. 78 interactors.
DIPiDIP-6161N.
IntActiP13804. 17 interactors.
MINTiMINT-5002447.
STRINGi9606.ENSP00000452762.

Structurei

Secondary structure

1333
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi21 – 25Combined sources5
Beta strandi28 – 31Combined sources4
Helixi36 – 45Combined sources10
Beta strandi49 – 58Combined sources10
Helixi61 – 69Combined sources9
Beta strandi75 – 80Combined sources6
Helixi82 – 84Combined sources3
Helixi89 – 103Combined sources15
Beta strandi106 – 113Combined sources8
Helixi114 – 127Combined sources14
Beta strandi132 – 135Combined sources4
Beta strandi137 – 140Combined sources4
Beta strandi143 – 148Combined sources6
Turni149 – 152Combined sources4
Beta strandi153 – 159Combined sources7
Beta strandi162 – 168Combined sources7
Helixi170 – 172Combined sources3
Beta strandi178 – 180Combined sources3
Beta strandi184 – 187Combined sources4
Beta strandi196 – 204Combined sources9
Helixi212 – 214Combined sources3
Beta strandi216 – 221Combined sources6
Helixi223 – 225Combined sources3
Helixi229 – 231Combined sources3
Helixi232 – 241Combined sources10
Beta strandi244 – 247Combined sources4
Helixi249 – 253Combined sources5
Helixi259 – 261Combined sources3
Beta strandi262 – 264Combined sources3
Beta strandi273 – 279Combined sources7
Helixi284 – 287Combined sources4
Turni288 – 292Combined sources5
Beta strandi294 – 301Combined sources8
Helixi306 – 309Combined sources4
Beta strandi312 – 317Combined sources6
Helixi319 – 329Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EFVX-ray2.10A20-333[»]
1T9GX-ray2.90R1-333[»]
2A1TX-ray2.80R1-333[»]
2A1UX-ray2.11A1-333[»]
ProteinModelPortaliP13804.
SMRiP13804.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13804.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni20 – 204Domain I1 PublicationAdd BLAST185
Regioni205 – 333Domain II1 PublicationAdd BLAST129

Domaini

Domain I shares an identical polypeptide fold with the beta subunit ETFB though there is no sequence similarity.1 Publication

Sequence similaritiesi

Belongs to the ETF alpha-subunit/FixB family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG3954. Eukaryota.
COG2025. LUCA.
GeneTreeiENSGT00390000013422.
HOGENOMiHOG000247865.
HOVERGENiHBG002317.
InParanoidiP13804.
KOiK03522.
OMAiCCIESID.
OrthoDBiEOG091G0EQM.
PhylomeDBiP13804.
TreeFamiTF105763.

Family and domain databases

CDDicd01715. ETF_alpha. 1 hit.
Gene3Di3.40.50.1220. 1 hit.
3.40.50.620. 1 hit.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR014730. ETF_a/b_N.
IPR001308. ETF_a/FixB.
IPR033947. ETF_alpha_N.
IPR014731. ETF_asu_C.
IPR018206. ETF_asu_C_CS.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PfamiPF01012. ETF. 1 hit.
PF00766. ETF_alpha. 1 hit.
[Graphical view]
PIRSFiPIRSF000089. Electra_flavoP_a. 1 hit.
SMARTiSM00893. ETF. 1 hit.
[Graphical view]
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS00696. ETF_ALPHA. 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: P13804-1) [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
MFRAAAPGQL RRAASLLRFQ STLVIAEHAN DSLAPITLNT ITAATRLGGE
60 70 80 90 100
VSCLVAGTKC DKVAQDLCKV AGIAKVLVAQ HDVYKGLLPE ELTPLILATQ
110 120 130 140 150
KQFNYTHICA GASAFGKNLL PRVAAKLEVA PISDIIAIKS PDTFVRTIYA
160 170 180 190 200
GNALCTVKCD EKVKVFSVRG TSFDAAATSG GSASSEKASS TSPVEISEWL
210 220 230 240 250
DQKLTKSDRP ELTGAKVVVS GGRGLKSGEN FKLLYDLADQ LHAAVGASRA
260 270 280 290 300
AVDAGFVPND MQVGQTGKIV APELYIAVGI SGAIQHLAGM KDSKTIVAIN
310 320 330
KDPEAPIFQV ADYGIVADLF KVVPEMTEIL KKK
Length:333
Mass (Da):35,080
Last modified:January 1, 1990 - v1
Checksum:i2EC6D1ADE68CBDB5
GO
Isoform 2 (identifier: P13804-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     14-62: Missing.

Note: No experimental confirmation available.
Show »
Length:284
Mass (Da):30,026
Checksum:i3AC6D1AA1BE79C6D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_002366116G → R in GA2A. 1 PublicationCorresponds to variant rs119458971dbSNPEnsembl.1
Natural variantiVAR_002367157V → G in GA2A. 1 PublicationCorresponds to variant rs119458969dbSNPEnsembl.1
Natural variantiVAR_008547171T → I.1 PublicationCorresponds to variant rs1801591dbSNPEnsembl.1
Natural variantiVAR_002368266T → M in GA2A. 1 PublicationCorresponds to variant rs119458970dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04324614 – 62Missing in isoform 2. 1 PublicationAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04058 mRNA. Translation: AAA52406.1.
S55815 mRNA. No translation available.
S55816 mRNA. No translation available.
AJ224002 Genomic DNA. Translation: CAA11802.1.
AF436657
, AF436646, AF436647, AF436648, AF436649, AF436650, AF436651, AF436652, AF436653, AF436654, AF436655, AF436656 Genomic DNA. Translation: AAN03712.1.
BT009796 mRNA. Translation: AAP88798.1.
AK292979 mRNA. Translation: BAF85668.1.
AK300044 mRNA. Translation: BAG61855.1.
AC027243 Genomic DNA. No translation available.
AC091100 Genomic DNA. No translation available.
CH471136 Genomic DNA. Translation: EAW99221.1.
BC015526 mRNA. Translation: AAH15526.1.
BC095457 mRNA. Translation: AAH95457.1.
CCDSiCCDS32299.1. [P13804-1]
CCDS45311.1. [P13804-2]
PIRiA31998.
RefSeqiNP_000117.1. NM_000126.3. [P13804-1]
NP_001121188.1. NM_001127716.1. [P13804-2]
UniGeneiHs.39925.

Genome annotation databases

EnsembliENST00000433983; ENSP00000399273; ENSG00000140374. [P13804-2]
ENST00000557943; ENSP00000452762; ENSG00000140374. [P13804-1]
GeneIDi2108.
KEGGihsa:2108.
UCSCiuc002bbt.3. human. [P13804-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04058 mRNA. Translation: AAA52406.1.
S55815 mRNA. No translation available.
S55816 mRNA. No translation available.
AJ224002 Genomic DNA. Translation: CAA11802.1.
AF436657
, AF436646, AF436647, AF436648, AF436649, AF436650, AF436651, AF436652, AF436653, AF436654, AF436655, AF436656 Genomic DNA. Translation: AAN03712.1.
BT009796 mRNA. Translation: AAP88798.1.
AK292979 mRNA. Translation: BAF85668.1.
AK300044 mRNA. Translation: BAG61855.1.
AC027243 Genomic DNA. No translation available.
AC091100 Genomic DNA. No translation available.
CH471136 Genomic DNA. Translation: EAW99221.1.
BC015526 mRNA. Translation: AAH15526.1.
BC095457 mRNA. Translation: AAH95457.1.
CCDSiCCDS32299.1. [P13804-1]
CCDS45311.1. [P13804-2]
PIRiA31998.
RefSeqiNP_000117.1. NM_000126.3. [P13804-1]
NP_001121188.1. NM_001127716.1. [P13804-2]
UniGeneiHs.39925.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EFVX-ray2.10A20-333[»]
1T9GX-ray2.90R1-333[»]
2A1TX-ray2.80R1-333[»]
2A1UX-ray2.11A1-333[»]
ProteinModelPortaliP13804.
SMRiP13804.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108409. 78 interactors.
DIPiDIP-6161N.
IntActiP13804. 17 interactors.
MINTiMINT-5002447.
STRINGi9606.ENSP00000452762.

PTM databases

iPTMnetiP13804.
PhosphoSitePlusiP13804.
SwissPalmiP13804.

Polymorphism and mutation databases

BioMutaiETFA.
DMDMi119636.

2D gel databases

UCD-2DPAGEP13804.

Proteomic databases

EPDiP13804.
PaxDbiP13804.
PeptideAtlasiP13804.
PRIDEiP13804.
TopDownProteomicsiP13804-1. [P13804-1]
P13804-2. [P13804-2]

Protocols and materials databases

DNASUi2108.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000433983; ENSP00000399273; ENSG00000140374. [P13804-2]
ENST00000557943; ENSP00000452762; ENSG00000140374. [P13804-1]
GeneIDi2108.
KEGGihsa:2108.
UCSCiuc002bbt.3. human. [P13804-1]

Organism-specific databases

CTDi2108.
DisGeNETi2108.
GeneCardsiETFA.
HGNCiHGNC:3481. ETFA.
HPAiHPA018990.
HPA018993.
HPA018996.
HPA024089.
MalaCardsiETFA.
MIMi231680. phenotype.
608053. gene.
neXtProtiNX_P13804.
OpenTargetsiENSG00000140374.
Orphaneti394532. Multiple acyl-CoA dehydrogenation deficiency, mild type.
394529. Multiple acyl-CoA dehydrogenation deficiency, severe neonatal type.
PharmGKBiPA27897.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3954. Eukaryota.
COG2025. LUCA.
GeneTreeiENSGT00390000013422.
HOGENOMiHOG000247865.
HOVERGENiHBG002317.
InParanoidiP13804.
KOiK03522.
OMAiCCIESID.
OrthoDBiEOG091G0EQM.
PhylomeDBiP13804.
TreeFamiTF105763.

Enzyme and pathway databases

BioCyciZFISH:ETFACLOS-MONOMER.
ReactomeiR-HSA-611105. Respiratory electron transport.

Miscellaneous databases

ChiTaRSiETFA. human.
EvolutionaryTraceiP13804.
GeneWikiiETFA.
GenomeRNAii2108.
PROiP13804.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140374.
CleanExiHS_ETFA.
ExpressionAtlasiP13804. baseline and differential.
GenevisibleiP13804. HS.

Family and domain databases

CDDicd01715. ETF_alpha. 1 hit.
Gene3Di3.40.50.1220. 1 hit.
3.40.50.620. 1 hit.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR014730. ETF_a/b_N.
IPR001308. ETF_a/FixB.
IPR033947. ETF_alpha_N.
IPR014731. ETF_asu_C.
IPR018206. ETF_asu_C_CS.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PfamiPF01012. ETF. 1 hit.
PF00766. ETF_alpha. 1 hit.
[Graphical view]
PIRSFiPIRSF000089. Electra_flavoP_a. 1 hit.
SMARTiSM00893. ETF. 1 hit.
[Graphical view]
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS00696. ETF_ALPHA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiETFA_HUMAN
AccessioniPrimary (citable) accession number: P13804
Secondary accession number(s): B4DT43, Q53XN3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: November 30, 2016
This is version 187 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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.