Reviewed, UniProtKB/Swiss-Prot P38117 (ETFB_HUMAN)

Names and origin

Protein names

Recommended name:
    Electron transfer flavoprotein subunit beta
      Short name=Beta-ETF

Gene names

Name:	ETFB
ORF Names:	FP585

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	255 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. Binds 1 AMP per subunit.
Subunit structure	Heterodimer of an alpha and a beta subunit.
Subcellular location	Mitochondrion matrix.
Tissue specificity	Abundant in liver, heart and skeletal muscle. A weak expression is seen in the brain, placenta, lung, kidney and pancreas.
Involvement in disease	Defects in ETFB are the cause of glutaric aciduria type 2B (GA2B) [MIM:231680]. GA2B is 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. Ref.2 Ref.7
Sequence similarities	Belongs to the ETF beta-subunit/fixA family.

Ontologies

Keywords
Biological process	Electron transport Transport
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Glutaricaciduria
Ligand	FAD Flavoprotein
PTM	Acetylation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial matrix Ref.1 Traceable author statement. Source: ProtInc
Molecular function	electron carrier activity Ref.7 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P38117-1)

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: P38117-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MAELRVLVAVKRVIDYAVK → MYLSLWVTIN...DPTPSPPAGQ

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 255

254

Electron transfer flavoprotein subunit beta

PRO_0000167870

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Natural variations

Alternative sequence

1 – 19

19

MAELR…DYAVK → MYLSLWVTINTVNLRNTLSG LRGAVTTVGMIKSDVPGTQE WLDERRRQGDLPLPTNSNPV LSLELCDPGQGPAPFQAVVV LIQPGRGLALRPPPSCLFPP DPTPSPPAGQ in isoform 2.

VSP_017850

Natural variant

128

1

D → N in GA2B. Ref.2

VAR_025804

Natural variant

154

1

T → M: dbSNP rs1130426. Ref.3 Ref.10

VAR_008548

Natural variant

164

1

R → Q in GA2B. Ref.7

VAR_002369

Experimental info

Sequence conflict

198

1

I → S Ref.3

Secondary structure

1

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255

Helix Strand Turn

Details...

Beta strand

5 – 9

5

Beta strand

12 – 14

3

Beta strand

26 – 29

4

Beta strand

36 – 38

3

Helix

40 – 54

15

Beta strand

59 – 68

10

Helix

71 – 81

11

Beta strand

84 – 90

7

Helix

93 – 96

4

Helix

101 – 115

15

Beta strand

118 – 124

7

Turn

127 – 129

3

Helix

134 – 142

9

Beta strand

146 – 156

11

Beta strand

159 – 166

8

Beta strand

169 – 183

15

Helix

185 – 187

3

Helix

195 – 200

6

Turn

201 – 203

3

Beta strand

206 – 209

4

Helix

211 – 214

4

Beta strand

221 – 228

8

Helix

242 – 251

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 47E6EAEF50EB2C80	FASTA	255	27,844
	10 20 30 40 50 60 MAELRVLVAV KRVIDYAVKI RVKPDRTGVV TDGVKHSMNP FCEIAVEEAV RLKEKKLVKE 70 80 90 100 110 120 VIAVSCGPAQ CQETIRTALA MGADRGIHVE VPPAEAERLG PLQVARVLAK LAEKEKVDLV 130 140 150 160 170 180 LLGKQAIDDD CNQTGQMTAG FLDWPQGTFA SQVTLEGDKL KVEREIDGGL ETLRLKLPAV 190 200 210 220 230 240 VTADLRLNEP RYATLPNIMK AKKKKIEVIK PGDLGVDLTS KLSVISVEDP PQRTAGVKVE 250 TTEDLVAKLK EIGRI
	Isoform 2. Checksum: 29C992C07350130A	FASTA	346	37,434
	10 20 30 40 50 60 MYLSLWVTIN TVNLRNTLSG LRGAVTTVGM IKSDVPGTQE WLDERRRQGD LPLPTNSNPV 70 80 90 100 110 120 LSLELCDPGQ GPAPFQAVVV LIQPGRGLAL RPPPSCLFPP DPTPSPPAGQ IRVKPDRTGV 130 140 150 160 170 180 VTDGVKHSMN PFCEIAVEEA VRLKEKKLVK EVIAVSCGPA QCQETIRTAL AMGADRGIHV 190 200 210 220 230 240 EVPPAEAERL GPLQVARVLA KLAEKEKVDL VLLGKQAIDD DCNQTGQMTA GFLDWPQGTF 250 260 270 280 290 300 ASQVTLEGDK LKVEREIDGG LETLRLKLPA VVTADLRLNE PRYATLPNIM KAKKKKIEVI 310 320 330 340 KPGDLGVDLT SKLSVISVED PPQRTAGVKV ETTEDLVAKL KEIGRI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and mitochondrial import of the beta-subunit of the human electron-transfer flavoprotein." Finocchiaro G., Colombo I., Garavaglia B., Gellera C., Valdameri G., Garbuglio N., Didonato S. Eur. J. Biochem. 213:1003-1008(1993) [PubMed: 8504797] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal liver.
[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: 12815589] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GA2B ASN-128.
[3]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed: 15498874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT MET-154.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Cerebellum.
[7]	"Mutations and polymorphisms of the gene encoding the beta-subunit of the electron transfer flavoprotein in three patients with glutaric acidemia type II." Colombo I., Finocchiaro G., Garavaglia B., Garbuglio N., Yamaguchi S., Frerman F., Berra B., Didonato S. Hum. Mol. Genet. 3:429-435(1994) [PubMed: 7912128] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 147-199, VARIANT GA2B GLN-164.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"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: 8962055] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[10]	"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: 10356313] [Abstract] Cited for: VARIANT MET-154.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

X71129 mRNA. Translation: CAA50441.1.
AF436663 , AF436658, AF436659, AF436660, AF436661, AF436662 Genomic DNA. Translation: AAN03713.1.
AF370381 mRNA. Translation: AAQ15217.1.
CR456827 mRNA. Translation: CAG33108.1.
AK055285 mRNA. Translation: BAG51494.1.
BC093961 mRNA. Translation: AAH93961.1.
BC093963 mRNA. Translation: AAH93963.1.
X76067 Genomic DNA. Translation: CAB37832.1.

IPI

IPI00004902.
IPI00556451.

PIR

S32482.

RefSeq

NP_001014763.1.
NP_001976.1.

UniGene

Hs.654553

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EFV	X-ray	2.10	B	1-255	[»]
1T9G	X-ray	2.90	S	1-255	[»]
2A1T	X-ray	2.80	S	1-255	[»]
2A1U	X-ray	2.11	B	1-255	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:6162N.

IntAct

P38117. 2 interactions.

STRING

P38117.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00004902.

Proteomic databases

PeptideAtlas

P38117.

PRIDE

P38117.

Genome annotation databases

Ensembl

ENST00000309244; ENSP00000311930; ENSG00000105379; Homo sapiens. [Genome view]
ENST00000354232; ENSP00000346173; ENSG00000105379; Homo sapiens. [Genome view]

GeneID

2109.

KEGG

hsa:2109.

UCSC

uc002pwg.1. human.
uc002pwh.1. human.

Organism-specific databases

CTD

2109.

GeneCards

GC19M056540.

H-InvDB

HIX0015381.

HGNC

HGNC:3482. ETFB.

HPA

HPA018910.
HPA018921.
HPA018923.

MIM

130410. gene.
231680. phenotype.

Orphanet

25. Glutaryl-CoA dehydrogenase deficiency.
26791. Multiple FAD dehydrogenase deficiency.

PharmGKB

PA27898.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P38117.

OMA

KNEAGVI.

Enzyme and pathway databases

Reactome

REACT_1505. Integration of energy metabolism.
REACT_15380. Diabetes pathways.

Gene expression databases

ArrayExpress

P38117.

Bgee

P38117.

CleanEx

HS_ETFB.

Genevestigator

P38117.

GermOnline

ENSG00000105379. Homo sapiens.

Family and domain databases

InterPro

IPR000049. ET-Flavoprotein_bsu_CS.
IPR014730. ETF_a/b_N.
IPR012255. ETF_b.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]

Gene3D

G3DSA:3.40.50.620. Rossmann-like_a/b/a_fold. 1 hit.

PANTHER

PTHR21294. Beta-ETF. 1 hit.

Pfam

PF01012. ETF. 1 hit.
[Graphical view]

PIRSF

PIRSF000090. Beta-ETF. 1 hit.

ProDom

PD003528. ETF_beta. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS01065. ETF_BETA. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

8527.

SOURCE

Search...

Entry information

Entry name

ETFB_HUMAN

Accession

Primary (citable) accession number: P38117
Secondary accession number(s): B3KNY2 , Q6IBH7, Q71RF6, Q9Y3S7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	January 23, 2007
Last modified:	November 3, 2009
This is version 109 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.