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P13804 (ETFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Electron transfer flavoprotein subunit alpha, mitochondrial

Short name=Alpha-ETF
Gene names
Name:ETFA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length333 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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).

Cofactor

Binds 1 FAD per dimer.

Subunit structure

Heterodimer of an alpha and a beta subunit.

Subcellular location

Mitochondrion matrix.

Post-translational modification

The N-terminus is blocked.

Involvement in disease

Glutaric aciduria 2A (GA2A) [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. Ref.11 Ref.12

Sequence similarities

Belongs to the ETF alpha-subunit/FixB family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P13804-1)

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.
Isoform 2 (identifier: P13804-2)

The sequence of this isoform differs from the canonical sequence as follows:
     14-62: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – ?Mitochondrion Potential
Chain? – 333Electron transfer flavoprotein subunit alpha, mitochondrialPRO_0000008650

Regions

Nucleotide binding274 – 30229FAD Potential

Amino acid modifications

Modified residue591N6-acetyllysine; alternate By similarity
Modified residue591N6-succinyllysine; alternate By similarity
Modified residue621N6-acetyllysine By similarity
Modified residue691N6-acetyllysine; alternate By similarity
Modified residue691N6-succinyllysine; alternate By similarity
Modified residue751N6-acetyllysine By similarity
Modified residue851N6-acetyllysine; alternate By similarity
Modified residue851N6-succinyllysine; alternate By similarity
Modified residue1011N6-acetyllysine By similarity
Modified residue1391N6-acetyllysine By similarity
Modified residue1581N6-acetyllysine; alternate By similarity
Modified residue1581N6-succinyllysine; alternate By similarity
Modified residue1641N6-acetyllysine By similarity
Modified residue1871N6-succinyllysine By similarity
Modified residue2031N6-acetyllysine; alternate By similarity
Modified residue2031N6-succinyllysine; alternate By similarity
Modified residue2161N6-succinyllysine By similarity
Modified residue2261N6-acetyllysine; alternate By similarity
Modified residue2261N6-succinyllysine; alternate By similarity
Modified residue2321N6-acetyllysine; alternate By similarity
Modified residue2321N6-succinyllysine; alternate By similarity
Modified residue3011N6-succinyllysine By similarity

Natural variations

Alternative sequence14 – 6249Missing in isoform 2.
VSP_043246
Natural variant1161G → R in GA2A. Ref.12
VAR_002366
Natural variant1571V → G in GA2A. Ref.11
VAR_002367
Natural variant1711T → I. Ref.13
Corresponds to variant rs1801591 [ dbSNP | Ensembl ].
VAR_008547
Natural variant2661T → M in GA2A. Ref.12
VAR_002368

Secondary structure

................................................................... 333
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1990. Version 1.
Checksum: 2EC6D1ADE68CBDB5

FASTA33335,080
        10         20         30         40         50         60 
MFRAAAPGQL RRAASLLRFQ STLVIAEHAN DSLAPITLNT ITAATRLGGE VSCLVAGTKC 

        70         80         90        100        110        120 
DKVAQDLCKV AGIAKVLVAQ HDVYKGLLPE ELTPLILATQ KQFNYTHICA GASAFGKNLL 

       130        140        150        160        170        180 
PRVAAKLEVA PISDIIAIKS PDTFVRTIYA GNALCTVKCD EKVKVFSVRG TSFDAAATSG 

       190        200        210        220        230        240 
GSASSEKASS TSPVEISEWL DQKLTKSDRP ELTGAKVVVS GGRGLKSGEN FKLLYDLADQ 

       250        260        270        280        290        300 
LHAAVGASRA AVDAGFVPND MQVGQTGKIV APELYIAVGI SGAIQHLAGM KDSKTIVAIN 

       310        320        330 
KDPEAPIFQV ADYGIVADLF KVVPEMTEIL KKK 

« Hide

Isoform 2 [UniParc].

Checksum: 3AC6D1AA1BE79C6D
Show »

FASTA28430,026

References

« Hide 'large scale' references
[1]"Molecular cloning and nucleotide sequence of cDNAs encoding the alpha-subunit of human electron transfer flavoprotein."
Finocchiaro G., Ito M., Ikeda Y., Tanaka K.
J. Biol. Chem. 263:15773-15780(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency."
Olsen R.K.J., Andresen B.S., Christensen E., Bross P., Skovby F., Gregersen N.
Hum. Mutat. 22:12-23(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Trachea.
[5]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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] (ISOFORM 1).
Tissue: Chondrosarcoma and Colon.
[8]Lubec G., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 86-101 AND 170-203, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Fetal brain cortex.
[9]"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].
[10]"Three-dimensional structure of human electron transfer flavoprotein to 2.1-A resolution."
Roberts D.L., Frerman F.E., Kim J.-J.P.
Proc. Natl. Acad. Sci. U.S.A. 93:14355-14360(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[11]"Molecular characterization of variant alpha-subunit of electron transfer flavoprotein in three patients with glutaric acidemia type II -- and identification of glycine substitution for valine-157 in the sequence of the precursor, producing an unstable mature protein in a patient."
Indo Y., Glassberg R., Yokota I., Tanaka K.
Am. J. Hum. Genet. 49:575-580(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GA2A GLY-157.
[12]"Glutaric acidemia type II. Heterogeneity in beta-oxidation flux, polypeptide synthesis, and complementary DNA mutations in the alpha subunit of electron transfer flavoprotein in eight patients."
Freneaux E., Sheffield V.C., Molin L., Shires A., Rhead W.
J. Clin. Invest. 90:1679-1686(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GA2A ARG-116 AND MET-266.
[13]"A polymorphic variant in the human electron transfer flavoprotein alpha-chain (alpha-T171) displays decreased thermal stability and is overrepresented in very-long-chain acyl-CoA dehydrogenase-deficient patients with mild childhood presentation."
Bross P., Pedersen P., Winter V., Nyholm M., Johansen B.N., Olsen R.K., Corydon M.J., Andresen B.S., Eiberg H., Kolvraa S., Gregersen N.
Mol. Genet. Metab. 67:138-147(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ILE-171.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04058 mRNA. Translation: AAA52406.1.
S55815 mRNA. No translation available.
S55816 mRNA. No translation available.
AJ224002 Genomic DNA. Translation: CAA11802.1.
AF436657 expand/collapse EMBL AC list , 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.
CCDSCCDS32299.1. [P13804-1]
CCDS45311.1. [P13804-2]
PIRA31998.
RefSeqNP_000117.1. NM_000126.3. [P13804-1]
NP_001121188.1. NM_001127716.1. [P13804-2]
UniGeneHs.39925.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EFVX-ray2.10A20-333[»]
1T9GX-ray2.90R1-333[»]
2A1TX-ray2.80R1-333[»]
2A1UX-ray2.11A1-333[»]
ProteinModelPortalP13804.
SMRP13804. Positions 20-331.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108409. 15 interactions.
DIPDIP-6161N.
IntActP13804. 7 interactions.
MINTMINT-5002447.
STRING9606.ENSP00000267950.

PTM databases

PhosphoSiteP13804.

Polymorphism databases

DMDM119636.

2D gel databases

UCD-2DPAGEP13804.

Proteomic databases

MaxQBP13804.
PaxDbP13804.
PeptideAtlasP13804.
PRIDEP13804.

Protocols and materials databases

DNASU2108.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000433983; ENSP00000399273; ENSG00000140374. [P13804-2]
ENST00000557943; ENSP00000452762; ENSG00000140374. [P13804-1]
GeneID2108.
KEGGhsa:2108.
UCSCuc002bbt.2. human. [P13804-1]
uc010bkq.1. human. [P13804-2]

Organism-specific databases

CTD2108.
GeneCardsGC15M076508.
HGNCHGNC:3481. ETFA.
HPAHPA018990.
HPA018993.
HPA018996.
HPA024089.
MIM231680. phenotype.
608053. gene.
neXtProtNX_P13804.
Orphanet394532. Multiple acyl-CoA dehydrogenation deficiency, mild type.
394529. Multiple acyl-CoA dehydrogenation deficiency, severe neonatal type.
PharmGKBPA27897.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2025.
HOGENOMHOG000247865.
HOVERGENHBG002317.
InParanoidP13804.
KOK03522.
OMATITAAKH.
OrthoDBEOG76MK8R.
PhylomeDBP13804.
TreeFamTF105763.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP13804.
BgeeP13804.
CleanExHS_ETFA.
GenevestigatorP13804.

Family and domain databases

Gene3D3.40.50.1220. 1 hit.
3.40.50.620. 1 hit.
InterProIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR001308. ETF_a.
IPR014730. ETF_a/b_N.
IPR014731. ETF_asu_C.
IPR018206. ETF_asu_C_CS.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PfamPF01012. ETF. 1 hit.
PF00766. ETF_alpha. 1 hit.
[Graphical view]
PIRSFPIRSF000089. Electra_flavoP_a. 1 hit.
SMARTSM00893. ETF. 1 hit.
[Graphical view]
SUPFAMSSF52467. SSF52467. 1 hit.
PROSITEPS00696. ETF_ALPHA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP13804.
GeneWikiETFA.
GenomeRNAi2108.
NextBio8523.
PROP13804.
SOURCESearch...

Entry information

Entry nameETFA_HUMAN
AccessionPrimary (citable) accession number: P13804
Secondary accession number(s): B4DT43, Q53XN3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: July 9, 2014
This is version 162 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 15

Human chromosome 15: entries, gene names and cross-references to MIM