P13804 (ETFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Electron transfer flavoprotein subunit alpha, mitochondrial
Short name=Alpha-ETF

Gene names

Name:

ETFA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	333 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Electron transport Transport
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Glutaricaciduria
Domain	Transit peptide
Ligand	FAD Flavoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	respiratory electron transport chain Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	electron carrier activity Inferred from direct assay PubMed 10423253. Source: UniProtKB flavin adenine dinucleotide binding Inferred from direct assay PubMed 10423253PubMed 9334218. Source: UniProtKB oxidoreductase activity Inferred from direct assay PubMed 10423253PubMed 9334218. Source: UniProtKB
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – ?

Mitochondrion Potential

Chain

? – 333

Electron transfer flavoprotein subunit alpha, mitochondrial

PRO_0000008650

Regions

Nucleotide binding

274 – 302

29

FAD Potential

Natural variations

Alternative sequence

14 – 62

49

Missing in isoform 2.

VSP_043246

Natural variant

116

1

G → R in GA2A. Ref.12

VAR_002366

Natural variant

157

1

V → G in GA2A. Ref.11

VAR_002367

Natural variant

171

1

T → I. Ref.13
Corresponds to variant rs1801591 [ dbSNP | Ensembl ].

VAR_008547

Natural variant

266

1

T → M in GA2A. Ref.12

VAR_002368

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

333

Helix Strand Turn

Details...

Beta strand

21 – 25

5

Beta strand

28 – 31

4

Helix

36 – 45

10

Beta strand

49 – 58

10

Helix

61 – 69

9

Beta strand

75 – 80

6

Helix

82 – 84

3

Helix

89 – 103

15

Beta strand

106 – 113

8

Helix

114 – 127

14

Beta strand

132 – 135

4

Beta strand

137 – 140

4

Beta strand

143 – 148

6

Turn

149 – 152

4

Beta strand

153 – 159

7

Beta strand

162 – 168

7

Helix

170 – 172

3

Beta strand

178 – 180

3

Beta strand

184 – 187

4

Beta strand

196 – 204

9

Helix

212 – 214

3

Beta strand

216 – 221

6

Helix

223 – 225

3

Helix

229 – 231

3

Helix

232 – 241

10

Beta strand

244 – 247

4

Helix

249 – 253

5

Helix

259 – 261

3

Beta strand

262 – 264

3

Beta strand

273 – 279

7

Helix

284 – 287

4

Turn

288 – 292

5

Beta strand

294 – 301

8

Helix

306 – 309

4

Beta strand

312 – 317

6

Helix

319 – 329

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: 2EC6D1ADE68CBDB5	FASTA	333	35,080
	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
	Isoform 2 [UniParc]. Checksum: 3AC6D1AA1BE79C6D	FASTA	284	30,026
	10 20 30 40 50 60 MFRAAAPGQL RRAVAQDLCK VAGIAKVLVA QHDVYKGLLP EELTPLILAT QKQFNYTHIC 70 80 90 100 110 120 AGASAFGKNL LPRVAAKLEV APISDIIAIK SPDTFVRTIY AGNALCTVKC DEKVKVFSVR 130 140 150 160 170 180 GTSFDAAATS GGSASSEKAS STSPVEISEW LDQKLTKSDR PELTGAKVVV SGGRGLKSGE 190 200 210 220 230 240 NFKLLYDLAD QLHAAVGASR AAVDAGFVPN DMQVGQTGKI VAPELYIAVG ISGAIQHLAG 250 260 270 280 MKDSKTIVAI NKDPEAPIFQ VADYGIVADL FKVVPEMTEI LKKK

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, 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.

Web resources

GeneReviews

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 , 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.

IPI

IPI00010810.

PIR

A31998.

RefSeq

NP_000117.1. NM_000126.3.
NP_001121188.1. NM_001127716.1.

UniGene

Hs.39925.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EFV	X-ray	2.10	A	20-333	[»]
1T9G	X-ray	2.90	R	1-333	[»]
2A1T	X-ray	2.80	R	1-333	[»]
2A1U	X-ray	2.11	A	1-333	[»]

ProteinModelPortal

P13804.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6161N.

IntAct

P13804. 6 interactions.

STRING

9606.ENSP00000267950.

PTM databases

PhosphoSite

P13804.

Polymorphism databases

DMDM

119636.

2D gel databases

UCD-2DPAGE

P13804.

Proteomic databases

PaxDb

P13804.

PeptideAtlas

P13804.

PRIDE

P13804.

Protocols and materials databases

DNASU

2108.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000433983; ENSP00000399273; ENSG00000140374.
ENST00000557943; ENSP00000452762; ENSG00000140374.

GeneID

2108.

KEGG

hsa:2108.

UCSC

uc002bbt.2. human.

Organism-specific databases

CTD

2108.

GeneCards

GC15M076508.

HGNC

HGNC:3481. ETFA.

HPA

HPA018990.
HPA018993.
HPA018996.
HPA024089.

MIM

231680. phenotype.
608053. gene.

neXtProt

NX_P13804.

Orphanet

26791. Glutaric acidemia type 2.

PharmGKB

PA27897.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2025.

HOGENOM

HOG000247865.

HOVERGEN

HBG002317.

InParanoid

P13804.

KO

K03522.

OMA

NFKMLYD.

PhylomeDB

P13804.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P13804.

Bgee

P13804.

CleanEx

HS_ETFA.

Genevestigator

P13804.

GermOnline

ENSG00000140374. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.620. 1 hit.

InterPro

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]

Pfam

PF01012. ETF. 1 hit.
PF00766. ETF_alpha. 1 hit.
[Graphical view]

PIRSF

PIRSF000089. Electra_flavoP_a. 1 hit.

SMART

SM00893. ETF. 1 hit.
[Graphical view]

PROSITE

PS00696. ETF_ALPHA. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P13804.

GenomeRNAi

2108.

NextBio

8523.

SOURCE

Search...

Entry information

Entry name

ETFA_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 149 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.