Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Electron transfer flavoprotein subunit alpha, mitochondrial

Gene

ETFA

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

Functioni

Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase (PubMed:27499296, PubMed:15159392, PubMed:15975918, PubMed:9334218, PubMed:10356313). It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase) (PubMed:9334218). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism (PubMed:12815589, PubMed:1882842, PubMed:1430199).1 Publication1 Publication7 Publications

Caution

Cofactori

FAD3 PublicationsNote: Binds 1 FAD per dimer.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei223FADCombined sources2 Publications1
Binding sitei248FADCombined sources2 Publications1
Binding sitei300FADCombined sources2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi263 – 266FADCombined sources2 Publications4
Nucleotide bindingi281 – 286FADCombined sources2 Publications6
Nucleotide bindingi318 – 319FADCombined sources2 Publications2

GO - Molecular functioni

  • electron transfer activity Source: UniProtKB
  • flavin adenine dinucleotide binding Source: UniProtKB
  • oxidoreductase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processElectron transport, Transport
LigandFAD, Flavoprotein

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000140374.15
HGNCiHGNC:3481 ETFA
MIMi608053 gene
neXtProtiNX_P13804

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Glutaric aciduria 2A (GA2A)4 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; impaired protein stability and loss of electron transfer activity. 2 PublicationsCorresponds to variant dbSNP:rs119458971Ensembl.1
Natural variantiVAR_002367157V → G in GA2A. 1 PublicationCorresponds to variant dbSNP:rs119458969Ensembl.1
Natural variantiVAR_002368266T → M in GA2A; decreased electron transfer activity. 2 PublicationsCorresponds to variant dbSNP:rs119458970Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi249R → A: Loss of electron transfer activity. 1 Publication1

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-2DPAGEiP13804

PTM databases

CarbonylDBiP13804
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

Heterodimer composed of ETFA and ETFB (PubMed:8962055, PubMed:15159392, PubMed:15975918, PubMed:9334218). Identified in a complex that contains ETFA, ETFB and ETFRF1 (PubMed:27499296). Interaction with ETFRF1 promotes dissociation of the bound FAD and loss of electron transfer activity (PubMed:27499296).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HSCBQ8IWL33EBI-1052886,EBI-1805738

Protein-protein interaction databases

BioGridi10840984 interactors.
DIPiDIP-6161N
IntActiP13804 28 interactors.
MINTiP13804
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
OMAiSQFKFTH
OrthoDBiEOG091G0EQM
PhylomeDBiP13804
TreeFamiTF105763

Family and domain databases

CDDicd01715 ETF_alpha, 1 hit
Gene3Di3.40.50.6201 hit
InterProiView protein in InterPro
IPR029035 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
PfamiView protein in Pfam
PF01012 ETF, 1 hit
PF00766 ETF_alpha, 1 hit
PIRSFiPIRSF000089 Electra_flavoP_a, 1 hit
SMARTiView protein in SMART
SM00893 ETF, 1 hit
SUPFAMiSSF52467 SSF52467, 1 hit
PROSITEiView protein in PROSITE
PS00696 ETF_ALPHA, 1 hit

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; impaired protein stability and loss of electron transfer activity. 2 PublicationsCorresponds to variant dbSNP:rs119458971Ensembl.1
Natural variantiVAR_002367157V → G in GA2A. 1 PublicationCorresponds to variant dbSNP:rs119458969Ensembl.1
Natural variantiVAR_008547171T → I Decreased protein stability. 1 PublicationCorresponds to variant dbSNP:rs1801591Ensembl.1
Natural variantiVAR_002368266T → M in GA2A; decreased electron transfer activity. 2 PublicationsCorresponds to variant dbSNP:rs119458970Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiETFA_HUMAN
AccessioniPrimary (citable) accession number: P13804
Secondary accession number(s): B4DT43, Q53XN3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: March 28, 2018
This is version 196 of the entry and version 1 of the sequence. See 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