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Protein

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

Gene

DBT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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). Within this complex, 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.

Catalytic activityi

2-methylpropanoyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-(2-methylpropanoyl)dihydrolipoyl)lysine.

Cofactori

(R)-lipoateNote: Binds 1 lipoyl cofactor covalently.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei452Sequence analysis1
Active sitei456Sequence analysis1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-12007.
ZFISH:HS06432-MONOMER.
ZFISH:MONOMER-12007.
BRENDAi2.3.1.168. 2681.
ReactomeiR-HSA-389661. Glyoxylate metabolism and glycine degradation.
R-HSA-70895. Branched-chain amino acid catabolism.

Names & Taxonomyi

Protein namesi
Recommended name:
Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (EC:2.3.1.168)
Alternative name(s):
52 kDa mitochondrial autoantigen of primary biliary cirrhosis1 Publication
Branched chain 2-oxo-acid dehydrogenase complex component E22 Publications
Short name:
BCOADC-E22 Publications
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 namesi
Name:DBT
Synonyms:BCATE2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:2698. DBT.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial alpha-ketoglutarate dehydrogenase complex Source: ProtInc
  • mitochondrial matrix Source: Reactome
  • mitochondrial nucleoid Source: BHF-UCL
  • mitochondrion Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Patients with primary biliary cirrhosis (PBC) show autoantibodies against the E2 component of branched-chain alpha-keto acid dehydrogenase complex. PBC is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis.

Maple syrup urine disease 2 (MSUD2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated.
See also OMIM:248600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01509998I → M in MSUD2. 1 Publication1
Natural variantiVAR_004978276F → C in MSUD2. 1 Publication1
Natural variantiVAR_015100384G → S in MSUD2. 2 PublicationsCorresponds to variant rs12021720dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Maple syrup urine disease

Organism-specific databases

DisGeNETi1629.
MalaCardsiDBT.
MIMi248600. phenotype.
Orphaneti268145. Classic maple syrup urine disease.
268162. Intermediate maple syrup urine disease.
268173. Intermittent maple syrup urine disease.
268184. Thiamine-responsive maple syrup urine disease.
PharmGKBiPA27167.

Polymorphism and mutation databases

BioMutaiDBT.
DMDMi400668.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 61MitochondrionSequence analysisAdd BLAST61
ChainiPRO_000002048962 – 482Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrialAdd BLAST421

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei105N6-lipoyllysinePROSITE-ProRule annotationBy similarity1
Modified residuei133N6-succinyllysineBy similarity1
Modified residuei196N6-acetyllysine; alternateBy similarity1
Modified residuei196N6-succinyllysine; alternateBy similarity1
Modified residuei202N6-acetyllysineBy similarity1
Modified residuei220PhosphoserineCombined sources1
Modified residuei243N6-acetyllysineBy similarity1
Modified residuei250N6-acetyllysineBy similarity1
Modified residuei261N6-succinyllysineBy similarity1
Modified residuei289N6-acetyllysine; alternateBy similarity1
Modified residuei289N6-succinyllysine; alternateBy similarity1
Modified residuei295N6-acetyllysineCombined sources1
Modified residuei304N6-acetyllysineBy similarity1
Modified residuei435N6-acetyllysineBy similarity1
Modified residuei440N6-acetyllysine; alternateBy similarity1
Modified residuei440N6-succinyllysine; alternateBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP11182.
MaxQBiP11182.
PaxDbiP11182.
PeptideAtlasiP11182.
PRIDEiP11182.

PTM databases

iPTMnetiP11182.
PhosphoSitePlusiP11182.
SwissPalmiP11182.

Expressioni

Gene expression databases

BgeeiENSG00000137992.
CleanExiHS_DBT.
ExpressionAtlasiP11182. baseline and differential.
GenevisibleiP11182. HS.

Organism-specific databases

HPAiHPA026481.
HPA026485.
HPA026533.

Interactioni

Subunit structurei

Forms a 24-polypeptide structural core with octahedral symmetry.

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi107997. 46 interactors.
IntActiP11182. 22 interactors.
MINTiMINT-1161634.
STRINGi9606.ENSP00000359151.

Structurei

Secondary structure

1482
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi65 – 68Combined sources4
Beta strandi79 – 84Combined sources6
Beta strandi94 – 96Combined sources3
Beta strandi99 – 102Combined sources4
Beta strandi107 – 109Combined sources3
Beta strandi116 – 121Combined sources6
Beta strandi125 – 129Combined sources5
Beta strandi133 – 139Combined sources7
Helixi175 – 183Combined sources9
Helixi188 – 190Combined sources3
Helixi196 – 198Combined sources3
Helixi202 – 213Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K8MNMR-A62-145[»]
1K8ONMR-A62-145[»]
1ZWVNMR-A165-213[»]
2COONMR-A163-220[»]
3RNMX-ray2.40E/F165-213[»]
ProteinModelPortaliP11182.
SMRiP11182.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11182.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini64 – 139Lipoyl-bindingPROSITE-ProRule annotationAdd BLAST76

Sequence similaritiesi

Belongs to the 2-oxoacid dehydrogenase family.Curated
Contains 1 lipoyl-binding domain.PROSITE-ProRule annotationCurated

Keywords - Domaini

Lipoyl, Transit peptide

Phylogenomic databases

eggNOGiKOG0558. Eukaryota.
COG0508. LUCA.
HOGENOMiHOG000281564.
HOVERGENiHBG104085.
InParanoidiP11182.
KOiK09699.
OrthoDBiEOG091G0FJ3.
PhylomeDBiP11182.
TreeFamiTF314182.

Family and domain databases

Gene3Di3.30.559.10. 1 hit.
4.10.320.10. 1 hit.
InterProiIPR003016. 2-oxoA_DH_lipoyl-BS.
IPR001078. 2-oxoacid_DH_actylTfrase.
IPR015761. BCKDC_E2.
IPR000089. Biotin_lipoyl.
IPR023213. CAT-like_dom.
IPR004167. E3-bd.
IPR011053. Single_hybrid_motif.
[Graphical view]
PANTHERiPTHR23151:SF71. PTHR23151:SF71. 2 hits.
PfamiPF00198. 2-oxoacid_dh. 1 hit.
PF00364. Biotin_lipoyl. 1 hit.
PF02817. E3_binding. 1 hit.
[Graphical view]
SUPFAMiSSF47005. SSF47005. 1 hit.
SSF51230. SSF51230. 1 hit.
PROSITEiPS50968. BIOTINYL_LIPOYL. 1 hit.
PS00189. LIPOYL. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P11182-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAVRMLRTW SRNAGKLICV RYFQTCGNVH VLKPNYVCFF GYPSFKYSHP
60 70 80 90 100
HHFLKTTAAL RGQVVQFKLS DIGEGIREVT VKEWYVKEGD TVSQFDSICE
110 120 130 140 150
VQSDKASVTI TSRYDGVIKK LYYNLDDIAY VGKPLVDIET EALKDSEEDV
160 170 180 190 200
VETPAVSHDE HTHQEIKGRK TLATPAVRRL AMENNIKLSE VVGSGKDGRI
210 220 230 240 250
LKEDILNYLE KQTGAILPPS PKVEIMPPPP KPKDMTVPIL VSKPPVFTGK
260 270 280 290 300
DKTEPIKGFQ KAMVKTMSAA LKIPHFGYCD EIDLTELVKL REELKPIAFA
310 320 330 340 350
RGIKLSFMPF FLKAASLGLL QFPILNASVD ENCQNITYKA SHNIGIAMDT
360 370 380 390 400
EQGLIVPNVK NVQICSIFDI ATELNRLQKL GSVGQLSTTD LTGGTFTLSN
410 420 430 440 450
IGSIGGTFAK PVIMPPEVAI GALGSIKAIP RFNQKGEVYK AQIMNVSWSA
460 470 480
DHRVIDGATM SRFSNLWKSY LENPAFMLLD LK
Length:482
Mass (Da):53,487
Last modified:July 1, 1993 - v3
Checksum:iA7CA728C8F33D126
GO

Sequence cautioni

The sequence AAA35589 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAA64512 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti321Q → P in AAA64512 (PubMed:2742576).Curated1
Sequence conflicti354L → V in AAA64512 (PubMed:2742576).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01509998I → M in MSUD2. 1 Publication1
Natural variantiVAR_004978276F → C in MSUD2. 1 Publication1
Natural variantiVAR_015100384G → S in MSUD2. 2 PublicationsCorresponds to variant rs12021720dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS767.1.
PIRiA32422.
RefSeqiNP_001909.3. NM_001918.3.
UniGeneiHs.709187.

Genome annotation databases

EnsembliENST00000370132; ENSP00000359151; ENSG00000137992.
GeneIDi1629.
KEGGihsa:1629.
UCSCiuc001dta.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS767.1.
PIRiA32422.
RefSeqiNP_001909.3. NM_001918.3.
UniGeneiHs.709187.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K8MNMR-A62-145[»]
1K8ONMR-A62-145[»]
1ZWVNMR-A165-213[»]
2COONMR-A163-220[»]
3RNMX-ray2.40E/F165-213[»]
ProteinModelPortaliP11182.
SMRiP11182.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107997. 46 interactors.
IntActiP11182. 22 interactors.
MINTiMINT-1161634.
STRINGi9606.ENSP00000359151.

PTM databases

iPTMnetiP11182.
PhosphoSitePlusiP11182.
SwissPalmiP11182.

Polymorphism and mutation databases

BioMutaiDBT.
DMDMi400668.

Proteomic databases

EPDiP11182.
MaxQBiP11182.
PaxDbiP11182.
PeptideAtlasiP11182.
PRIDEiP11182.

Protocols and materials databases

DNASUi1629.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370132; ENSP00000359151; ENSG00000137992.
GeneIDi1629.
KEGGihsa:1629.
UCSCiuc001dta.4. human.

Organism-specific databases

CTDi1629.
DisGeNETi1629.
GeneCardsiDBT.
GeneReviewsiDBT.
H-InvDBHIX0000815.
HGNCiHGNC:2698. DBT.
HPAiHPA026481.
HPA026485.
HPA026533.
MalaCardsiDBT.
MIMi248600. phenotype.
248610. gene.
neXtProtiNX_P11182.
Orphaneti268145. Classic maple syrup urine disease.
268162. Intermediate maple syrup urine disease.
268173. Intermittent maple syrup urine disease.
268184. Thiamine-responsive maple syrup urine disease.
PharmGKBiPA27167.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0558. Eukaryota.
COG0508. LUCA.
HOGENOMiHOG000281564.
HOVERGENiHBG104085.
InParanoidiP11182.
KOiK09699.
OrthoDBiEOG091G0FJ3.
PhylomeDBiP11182.
TreeFamiTF314182.

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-12007.
ZFISH:HS06432-MONOMER.
ZFISH:MONOMER-12007.
BRENDAi2.3.1.168. 2681.
ReactomeiR-HSA-389661. Glyoxylate metabolism and glycine degradation.
R-HSA-70895. Branched-chain amino acid catabolism.

Miscellaneous databases

ChiTaRSiDBT. human.
EvolutionaryTraceiP11182.
GeneWikiiDBT_(gene).
GenomeRNAii1629.
PROiP11182.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137992.
CleanExiHS_DBT.
ExpressionAtlasiP11182. baseline and differential.
GenevisibleiP11182. HS.

Family and domain databases

Gene3Di3.30.559.10. 1 hit.
4.10.320.10. 1 hit.
InterProiIPR003016. 2-oxoA_DH_lipoyl-BS.
IPR001078. 2-oxoacid_DH_actylTfrase.
IPR015761. BCKDC_E2.
IPR000089. Biotin_lipoyl.
IPR023213. CAT-like_dom.
IPR004167. E3-bd.
IPR011053. Single_hybrid_motif.
[Graphical view]
PANTHERiPTHR23151:SF71. PTHR23151:SF71. 2 hits.
PfamiPF00198. 2-oxoacid_dh. 1 hit.
PF00364. Biotin_lipoyl. 1 hit.
PF02817. E3_binding. 1 hit.
[Graphical view]
SUPFAMiSSF47005. SSF47005. 1 hit.
SSF51230. SSF51230. 1 hit.
PROSITEiPS50968. BIOTINYL_LIPOYL. 1 hit.
PS00189. LIPOYL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiODB2_HUMAN
AccessioniPrimary (citable) accession number: P11182
Secondary accession number(s): B2R811, Q5VVL8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1993
Last modified: November 30, 2016
This is version 208 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.