P11182 (ODB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial
EC=2.3.1.168

Alternative name(s):
Branched-chain alpha-keto acid dehydrogenase complex component E2
Short name=BCKAD-E2
Short name=BCKADE2
Dihydrolipoamide acetyltransferase component of branched-chain alpha-keto acid dehydrogenase complex
Dihydrolipoamide branched chain transacylase
Dihydrolipoyllysine-residue (2-methylpropanoyl)transferase

Gene names

Name:	DBT
Synonyms:	BCATE2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	482 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 branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO2. It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3).
Catalytic activity	2-methylpropanoyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-(2-methylpropanoyl)dihydrolipoyl)lysine.
Cofactor	Binds 1 lipoyl cofactor covalently.
Subunit structure	Forms a 24-polypeptide structural core with octahedral symmetry.
Subcellular location	Mitochondrion matrix.
Involvement in disease	Defects in DBT are the cause of maple syrup urine disease type 2 (MSUD2) [MIM:248600]. MSUD is an autosomal recessive disorder characterized by mental and physical retardation, feeding problems, and a maple syrup odor to the urine. Ref.17 Ref.18
Miscellaneous	The catalytic function of this enzyme is to accept, and to transfer to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component.
Sequence similarities	Belongs to the 2-oxoacid dehydrogenase family. Contains 1 lipoyl-binding domain.
Sequence caution	The sequence AAA35589.1 differs from that shown. Reason: Erroneous initiation. The sequence AAA64512.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Mitochondrion
Disease	Disease mutation Maple syrup urine disease
Domain	Lipoyl Transit peptide
Molecular function	Acyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	branched chain family amino acid catabolic process Traceable author statement. Source: Reactome fatty-acyl-CoA biosynthetic process Inferred from electronic annotation. Source: InterPro
Cellular component	microtubule cytoskeleton Inferred from direct assay. Source: HPA mitochondrial alpha-ketoglutarate dehydrogenase complex Traceable author statement. Source: ProtInc mitochondrial nucleoid Inferred from direct assay. Source: BHF-UCL
Molecular function	cofactor binding Inferred from electronic annotation. Source: InterPro dihydrolipoyllysine-residue (2-methylpropanoyl)transferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 61

61

Mitochondrion Potential

Chain

62 – 482

421

Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial

PRO_0000020489

Regions

Domain

65 – 138

74

Lipoyl-binding

Sites

Active site

452

1

Potential

Active site

456

1

Potential

Amino acid modifications

Modified residue

105

1

N6-lipoyllysine By similarity

Modified residue

295

1

N6-acetyllysine Ref.13

Natural variations

Natural variant

98

1

I → M in MSUD2. Ref.18

VAR_015099

Natural variant

276

1

F → C in MSUD2. Ref.17

VAR_004978

Natural variant

384

1

G → S in MSUD2. Ref.7 Ref.18
Corresponds to variant rs12021720 [ dbSNP | Ensembl ].

VAR_015100

Experimental info

Sequence conflict

321

1

Q → P in AAA64512. Ref.4

Sequence conflict

354

1

L → V in AAA64512. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

482

Helix Strand Turn

Details...

Beta strand

65 – 68

4

Beta strand

79 – 84

6

Beta strand

94 – 96

3

Beta strand

99 – 102

4

Beta strand

107 – 109

3

Beta strand

116 – 121

6

Beta strand

133 – 139

7

Turn

144 – 146

3

Helix

175 – 183

9

Beta strand

188 – 193

6

Beta strand

196 – 198

3

Helix

202 – 210

9

Sequences

	Sequence		Length	Mass (Da)
	P11182 [UniParc]. Last modified July 1, 1993. Version 3. Checksum: A7CA728C8F33D126	FASTA	482	53,487
	10 20 30 40 50 60 MAAVRMLRTW SRNAGKLICV RYFQTCGNVH VLKPNYVCFF GYPSFKYSHP HHFLKTTAAL 70 80 90 100 110 120 RGQVVQFKLS DIGEGIREVT VKEWYVKEGD TVSQFDSICE VQSDKASVTI TSRYDGVIKK 130 140 150 160 170 180 LYYNLDDIAY VGKPLVDIET EALKDSEEDV VETPAVSHDE HTHQEIKGRK TLATPAVRRL 190 200 210 220 230 240 AMENNIKLSE VVGSGKDGRI LKEDILNYLE KQTGAILPPS PKVEIMPPPP KPKDMTVPIL 250 260 270 280 290 300 VSKPPVFTGK DKTEPIKGFQ KAMVKTMSAA LKIPHFGYCD EIDLTELVKL REELKPIAFA 310 320 330 340 350 360 RGIKLSFMPF FLKAASLGLL QFPILNASVD ENCQNITYKA SHNIGIAMDT EQGLIVPNVK 370 380 390 400 410 420 NVQICSIFDI ATELNRLQKL GSVGQLSTTD LTGGTFTLSN IGSIGGTFAK PVIMPPEVAI 430 440 450 460 470 480 GALGSIKAIP RFNQKGEVYK AQIMNVSWSA DHRVIDGATM SRFSNLWKSY LENPAFMLLD LK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The complete cDNA sequence for dihydrolipoyl transacylase (E2) of human branched-chain alpha-keto acid dehydrogenase complex." Lau K.S., Chuang J.L., Herring W.J., Danner D.J., Cox R.P., Chuang D.T. Biochim. Biophys. Acta 1132:319-321(1992) [PubMed: 1420314] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[2]	"Nucleotide sequence of a cDNA for branched chain acyltransferase with analysis of the deduced protein structure." Hummel K.B., Litwer S., Bradford A.P., Aitken A., Danner D.J., Yeaman S.J. J. Biol. Chem. 263:6165-6168(1988) [PubMed: 3245861] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Construction and nucleotide sequence of a cDNA encoding the full-length preprotein for human branched chain acyltransferase." Danner D.J., Litwer S., Herring W.J., Pruckler J. J. Biol. Chem. 264:7742-7746(1989) [PubMed: 2708389] [Abstract] Cited for: SEQUENCE REVISION.
[4]	"Complete primary structure of the transacylase (E2b) subunit of the human branched chain alpha-keto acid dehydrogenase complex." Nobukuni Y., Mitsubuchi H., Endo F., Matsuda I. Biochem. Biophys. Res. Commun. 161:1035-1041(1989) [PubMed: 2742576] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"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]. Tissue: Kidney.
[7]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-384.
[8]	Mural R.J., Istrail S., Sutton G.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].
[9]	"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]. Tissue: Skin.
[10]	"Conservation of primary structure in the lipoyl-bearing and dihydrolipoyl dehydrogenase binding domains of mammalian branched-chain alpha-keto acid dehydrogenase complex: molecular cloning of human and bovine transacylase (E2) cDNAs." Lau K.S., Griffin T.A., Hu C.-W.C., Chuang D.T. Biochemistry 27:1972-1981(1988) [PubMed: 2837277] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-313.
[11]	"Structure of the gene encoding dihydrolipoyl transacylase (E2) component of human branched chain alpha-keto acid dehydrogenase complex and characterization of an E2 pseudogene." Lau K.S., Herring W.J., Chuang J.L., McKean M., Danner D.J., Cox R.P., Chuang D.T. J. Biol. Chem. 267:24090-24096(1992) [PubMed: 1429740] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6.
[12]	"Differential processing of human and rat E1 alpha precursors of the branched-chain alpha-keto acid dehydrogenase complex caused by an N-terminal proline in the rat sequence." Wynn R.M., Kochi H., Cox R.P., Chuang D.T. Biochim. Biophys. Acta 1201:125-128(1994) [PubMed: 7918575] [Abstract] Cited for: PROTEIN SEQUENCE OF 47-81.
[13]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-295, MASS SPECTROMETRY.
[14]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Solution structure and dynamics of the lipoic acid-bearing domain of human mitochondrial branched-chain alpha-keto acid dehydrogenase complex." Chang C.-F., Chou H.-T., Chuang J.L., Chuang D.T., Huang T.-H. J. Biol. Chem. 277:15865-15873(2002) [PubMed: 11839747] [Abstract] Cited for: STRUCTURE BY NMR OF 62-145.
[16]	"Solution structure of the E3-binding domain of dihydrolipoamide branched chain transacylase." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 163-220.
[17]	"A 17-bp insertion and a Phe215-->Cys missense mutation in the dihydrolipoyl transacylase (E2) mRNA from a thiamine-responsive maple syrup urine disease patient WG-34." Fisher C.W., Lau K.S., Fisher C.R., Wynn R.M., Cox R.P., Chuang D.T. Biochem. Biophys. Res. Commun. 174:804-809(1991) [PubMed: 1847055] [Abstract] Cited for: VARIANT MSUD2 CYS-276.
[18]	"Molecular basis of intermittent maple syrup urine disease: novel mutations in the E2 gene of the branched-chain alpha-keto acid dehydrogenase complex." Tsuruta M., Mitsubuchi H., Mardy S., Miura Y., Hayashida Y., Kinugasa A., Ishitsu T., Matsuda I., Indo Y. J. Hum. Genet. 43:91-100(1998) [PubMed: 9621512] [Abstract] Cited for: VARIANTS MSUD2 MET-98 AND SER-384.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X66785 mRNA. Translation: CAA47285.1.
J03208 mRNA. Translation: AAA35589.1. Different initiation.
M27093 mRNA. Translation: AAA64512.1. Different initiation.
BT007372 mRNA. Translation: AAP36036.1.
AL445928 Genomic DNA. Translation: CAH72257.1.
AK313191 mRNA. Translation: BAG36008.1.
CH471097 Genomic DNA. Translation: EAW72963.1.
BC016675 mRNA. Translation: AAH16675.1.
M19301 mRNA. Translation: AAA59200.1. Sequence problems.
X68104 Genomic DNA. Translation: CAA48225.1.

IPI

IPI00003944.

PIR

A32422.

RefSeq

NP_001909.2. NM_001918.2.

UniGene

Hs.709187.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1K8M	NMR	-	A	62-145	[»]
1K8O	NMR	-	A	62-145	[»]
1ZWV	NMR	-	A	165-213	[»]
2COO	NMR	-	A	163-220	[»]
3RNM	X-ray	2.40	E/F	165-213	[»]

ProteinModelPortal

P11182.

SMR

P11182. Positions 62-147, 163-220, 249-482.

ModBase

Search...

Protein-protein interaction databases

IntAct

P11182. 4 interactions.

MINT

MINT-1161634.

STRING

P11182.

PTM databases

PhosphoSite

P11182.

Polymorphism databases

DMDM

400668.

Proteomic databases

PRIDE

P11182.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000370132; ENSP00000359151; ENSG00000137992.

GeneID

1629.

KEGG

hsa:1629.

Organism-specific databases

CTD

1629.

GeneCards

GC01M100652.

H-InvDB

HIX0000815.

HGNC

HGNC:2698. DBT.

HPA

HPA026481.
HPA026485.
HPA026533.

MIM

248600. phenotype.
248610. gene.

neXtProt

NX_P11182.

Orphanet

511. Maple syrup urine disease.

PharmGKB

PA27167.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05894.

GeneTree

ENSGT00560000077144.

HOGENOM

HBG630916.

HOVERGEN

HBG104085.

InParanoid

P11182.

OrthoDB

EOG4PRSQK.

PhylomeDB

P11182.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-12007.

BRENDA

2.3.1.168. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P11182.

Bgee

P11182.

CleanEx

HS_DBT.

Genevestigator

P11182.

GermOnline

ENSG00000137992. Homo sapiens.

Family and domain databases

InterPro

IPR003016. 2-oxoA_DH_lipoyl-BS.
IPR001078. 2-oxoacid_DH_actylTfrase.
IPR000089. Biotin_lipoyl.
IPR023213. CAT-like_dom.
IPR004167. E3-bd.
IPR015761. Lip_Acyl_TA.
IPR011053. Single_hybrid_motif.
[Graphical view]

Gene3D

G3DSA:3.30.559.10. CAT-like_dom. 1 hit.
G3DSA:4.10.320.10. E3_bd. 1 hit.

KO

K09699.

PANTHER

PTHR23151:SF11. Lip_Acyl_TA. 1 hit.

Pfam

PF00198. 2-oxoacid_dh. 1 hit.
PF00364. Biotin_lipoyl. 1 hit.
PF02817. E3_binding. 1 hit.
[Graphical view]

SUPFAM

SSF47005. E3_bd. 1 hit.
SSF51230. Hybrid_motif. 1 hit.

PROSITE

PS50968. BIOTINYL_LIPOYL. 1 hit.
PS00189. LIPOYL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

6684.

SOURCE

Search...

Entry information

Entry name

ODB2_HUMAN

Accession

Primary (citable) accession number: P11182
Secondary accession number(s): B2R811, Q5VVL8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1993
Last modified:	January 25, 2012
This is version 158 of the entry and version 3 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.