DBT

Protein identityUniProt · HPA

UniProt accession

P11182

Gene

DBT

Ensembl

ENSG00000137992

Chromosome

1

Canonical length

482 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

The branched-chain alpha-keto acid dehydrogenase complex (BCKD) is an inner-mitochondrial enzyme complex involved in the breakdown of the branched-chain amino acids isoleucine, leucine, and valine. The BCKD complex is thought to be composed of a core of 24 transacylase (E2) subunits, and associated decarboxylase (E1), dehydrogenase (E3), and regulatory subunits. This gene encodes the transacylase (E2) subunit. Mutations in this gene result in maple syrup urine disease, type 2. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

482 residues, UniProt reviewed canonical sequence.

>P11182|DBT
     1  MAAVRMLRTW SRNAGKLICV RYFQTCGNVH VLKPNYVCFF GYPSFKYSHP HHFLKTTAAL
    61  RGQVVQFKLS DIGEGIREVT VKEWYVKEGD TVSQFDSICE VQSDKASVTI TSRYDGVIKK
   121  LYYNLDDIAY VGKPLVDIET EALKDSEEDV VETPAVSHDE HTHQEIKGRK TLATPAVRRL
   181  AMENNIKLSE VVGSGKDGRI LKEDILNYLE KQTGAILPPS PKVEIMPPPP KPKDMTVPIL
   241  VSKPPVFTGK DKTEPIKGFQ KAMVKTMSAA LKIPHFGYCD EIDLTELVKL REELKPIAFA
   301  RGIKLSFMPF FLKAASLGLL QFPILNASVD ENCQNITYKA SHNIGIAMDT EQGLIVPNVK
   361  NVQICSIFDI ATELNRLQKL GSVSQLSTTD LTGGTFTLSN IGSIGGTFAK PVIMPPEVAI
   421  GALGSIKAIP RFNQKGEVYK AQIMNVSWSA DHRVIDGATM SRFSNLWKSY LENPAFMLLD
   481  LK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DBT can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.42

Highest tissue expression

41 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DBT.

Disease | AllUniProt

Conditions DBT is implicated in, by any mechanism.

• Maple syrup urine disease 2 (MSUD2) MIM:620699

Disease | GeneticClinVar

166 pathogenic / likely-pathogenic of 850 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Maple syrup urine disease
• Maple syrup urine disease type 2
• Maple syrup urine disease type 1A
• DBT-related disorder
• See cases

ReferencesPubMed · IEDB

Publications for DBT from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.82

gnomAD pLI

0

gnomAD missense Z

0.99

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA
• branched-chain amino acid catabolic process

Molecular functions

• acyltransferase activity, transferring groups other than amino-acyl groups
• ubiquitin protein ligase binding
• dihydrolipoamide branched chain acyltransferase activity

Cellular components

• branched-chain alpha-ketoacid dehydrogenase complex
• cytosol
• microtubule cytoskeleton
• mitochondrial matrix
• mitochondrial nucleoid
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Biotin/lipoyl attachment
• 2-oxoacid dehydrogenase acyltransferase, catalytic domain
• 2-oxo acid dehydrogenase, lipoyl-binding site
• Peripheral subunit-binding domain
• Single hybrid motif
• Chloramphenicol acetyltransferase-like domain superfamily
• E3-binding domain superfamily
• 2-oxoacid dehydrogenases acyltransferase (catalytic domain)
• Biotin-requiring enzyme
• e3 binding domain
• 2-oxoacid dehydrogenase family, E2 component

KeywordsUniProt

• Acetylation
• Acyltransferase
• Lipoyl
• Maple syrup urine disease
• Mitochondrion
• Phosphoprotein
• Transferase
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of DBT in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HINT2
• MRRF