Q16134 (ETFD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial
Short name=ETF-QO
Short name=ETF-ubiquinone oxidoreductase
EC=1.5.5.1

Alternative name(s):
Electron-transferring-flavoprotein dehydrogenase
Short name=ETF dehydrogenase

Gene names

Name:

ETFDH

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	617 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	Accepts electrons from ETF and reduces ubiquinone.
Catalytic activity	Reduced electron-transferring flavoprotein + ubiquinone = electron-transferring flavoprotein + ubiquinol.
Cofactor	Binds 1 4Fe-4S cluster. FAD.
Subunit structure	Monomer.
Subcellular location	Mitochondrion inner membrane.
Involvement in disease	Glutaric aciduria 2C (GA2C) [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.
Sequence similarities	Belongs to the ETF-QO/FixC family. Contains 1 4Fe-4S ferredoxin-type domain.
Sequence caution	The sequence CAD98030.1 differs from that shown. Reason: Aberrant splicing.

Ontologies

Keywords
Biological process	Electron transport Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Disease	Glutaricaciduria
Domain	Transit peptide
Ligand	4Fe-4S FAD Flavoprotein Iron Iron-sulfur Metal-binding Ubiquinone
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fatty acid beta-oxidation using acyl-CoA dehydrogenase Inferred from mutant phenotype PubMed 17412732. Source: BHF-UCL respiratory electron transport chain Traceable author statement. Source: Reactome response to oxidative stress Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	integral to mitochondrial inner membrane Inferred from direct assay Ref.1. Source: UniProtKB mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from direct assay PubMed 18037314. Source: UniProtKB electron carrier activity Inferred from direct assay PubMed 12049629Ref.1. Source: UniProtKB electron-transferring-flavoprotein dehydrogenase activity Inferred from direct assay PubMed 12049629PubMed 14640977Ref.1. Source: UniProtKB flavin adenine dinucleotide binding Inferred from sequence or structural similarity PubMed 17050691. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, oxidizing metal ions with flavin as acceptor Inferred from sequence or structural similarity. Source: UniProtKB ubiquinone binding Inferred from direct assay PubMed 14640977. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 33	33	Mitochondrion Potential
	Chain	34 – 617	584	Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial		PRO_0000008661
Regions
	Intramembrane	109 – 130	22	By similarity
	Intramembrane	428 – 447	20	By similarity
	Domain	577 – 606	30	4Fe-4S ferredoxin-type
	Nucleotide binding	71 – 85	15	FAD Potential
Sites
	Metal binding	561	1	Iron-sulfur (4Fe-4S) Potential
	Metal binding	586	1	Iron-sulfur (4Fe-4S) Potential
	Metal binding	589	1	Iron-sulfur (4Fe-4S) Potential
	Metal binding	592	1	Iron-sulfur (4Fe-4S) Potential
	Binding site	305	1	Ubiquinone; via carbonyl oxygen By similarity
	Binding site	306	1	Ubiquinone; via amide nitrogen By similarity
Amino acid modifications
	Modified residue	96	1	N6-acetyllysine By similarity
	Modified residue	153	1	N6-acetyllysine By similarity
	Modified residue	223	1	N6-acetyllysine By similarity
	Modified residue	344	1	N6-acetyllysine By similarity
Natural variations
	Natural variant	31	1	T → I. Ref.1 Ref.2 Ref.4 Corresponds to variant rs11559290 [ dbSNP | Ensembl ].		VAR_062966
	Natural variant	94	1	H → R. Corresponds to variant rs1140065 [ dbSNP | Ensembl ].		VAR_055711
	Natural variant	565	1	V → L in a colorectal cancer sample; somatic mutation. Ref.6		VAR_036134
Experimental info
	Sequence conflict	109	1	I → V in CAD98030. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q16134 [UniParc]. Last modified March 23, 2010. Version 2. Checksum: 099EBA36C59AF3D6	FASTA	617	68,495
	10 20 30 40 50 60 MLVPLAKLSC LAYQCFHALK IKKNYLPLCA TRWSSTSTVP RITTHYTIYP RDKDKRWEGV 70 80 90 100 110 120 NMERFAEEAD VVIVGAGPAG LSAAVRLKQL AVAHEKDIRV CLVEKAAQIG AHTLSGACLD 130 140 150 160 170 180 PGAFKELFPD WKEKGAPLNT PVTEDRFGIL TEKYRIPVPI LPGLPMNNHG NYIVRLGHLV 190 200 210 220 230 240 SWMGEQAEAL GVEVYPGYAA AEVLFHDDGS VKGIATNDVG IQKDGAPKAT FERGLELHAK 250 260 270 280 290 300 VTIFAEGCHG HLAKQLYKKF DLRANCEPQT YGIGLKELWV IDEKNWKPGR VDHTVGWPLD 310 320 330 340 350 360 RHTYGGSFLY HLNEGEPLVA LGLVVGLDYQ NPYLSPFREF QRWKHHPSIR PTLEGGKRIA 370 380 390 400 410 420 YGARALNEGG FQSIPKLTFP GGLLIGCSPG FMNVPKIKGT HTAMKSGILA AESIFNQLTS 430 440 450 460 470 480 ENLQSKTIGL HVTEYEDNLK NSWVWKELYS VRNIRPSCHG VLGVYGGMIY TGIFYWILRG 490 500 510 520 530 540 MEPWTLKHKG SDFERLKPAK DCTPIEYPKP DGQISFDLLS SVALSGTNHE HDQPAHLTLR 550 560 570 580 590 600 DDSIPVNRNL SIYDGPEQRF CPAGVYEFVP VEQGDGFRLQ INAQNCVHCK TCDIKDPSQN 610 INWVVPEGGG GPAYNGM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of a cDNA encoding human electron transfer flavoprotein-ubiquinone oxidoreductase." Goodman S.I., Axtell K.M., Bindoff L.A., Beard S.E., Gill R.E., Frerman F.E. Eur. J. Biochem. 219:277-286(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-31. Tissue: Fetal liver.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-31. Tissue: Small intestine.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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], VARIANT ILE-31. Tissue: Lung.
[5]	"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].
[6]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-565.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	S69232 mRNA. Translation: AAC60628.1. BX538129 mRNA. Translation: CAD98030.1. Sequence problems. AC107219 Genomic DNA. No translation available. BC011890 mRNA. Translation: AAH11890.1.
IPI	IPI00032875.
PIR	S41115.
RefSeq	NP_004444.2. NM_004453.2.
UniGene	Hs.155729.
3D structure databases
ProteinModelPortal	Q16134.
SMR	Q16134. Positions 39-617.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q16134. 1 interaction.
STRING	9606.ENSP00000303552.
PTM databases
PhosphoSite	Q16134.
Polymorphism databases
DMDM	292495008.
Proteomic databases
PaxDb	Q16134.
PRIDE	Q16134.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000511912; ENSP00000426638; ENSG00000171503.
GeneID	2110.
KEGG	hsa:2110.
UCSC	uc003iqb.3. human.
Organism-specific databases
CTD	2110.
GeneCards	GC04P159593.
H-InvDB	HIX0200647.
HGNC	HGNC:3483. ETFDH.
HPA	HPA041978.
MIM	231675. gene. 231680. phenotype.
neXtProt	NX_Q16134.
Orphanet	26791. Glutaric acidemia type 2.
PharmGKB	PA27899.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0644.
HOGENOM	HOG000259450.
HOVERGEN	HBG005615.
InParanoid	Q16134.
KO	K00311.
OMA	EKDIRVC.
PhylomeDB	Q16134.
Enzyme and pathway databases
BioCyc	MetaCyc:HS10326-MONOMER.
BRENDA	1.5.5.1. 2681.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q16134.
Bgee	Q16134.
CleanEx	HS_ETFDH.
Genevestigator	Q16134.
GermOnline	ENSG00000171503. Homo sapiens.
Family and domain databases
InterPro	IPR017896. 4Fe4S_Fe-S-bd. IPR007859. ETFD_OxRdtase. IPR000103. Pyridine_nuc-diS_OxRdtase_2. [Graphical view]
Pfam	PF05187. ETF_QO. 1 hit. [Graphical view]
PRINTS	PR00469. PNDRDTASEII.
PROSITE	PS51379. 4FE4S_FER_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ETFDH. human.
GenomeRNAi	2110.
NextBio	8533.
SOURCE	Search...

Entry information

Entry name

ETFD_HUMAN

Accession

Primary (citable) accession number: Q16134
Secondary accession number(s): Q7Z347

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	March 23, 2010
Last modified:	May 1, 2013
This is version 130 of the entry and version 2 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.