chain
-
transit peptide:1-61
-
chain:62-482
checksum
A6CE6E8D532E10FA
comment
-
FUNCTION The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). 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 ACTIVITY N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 2-methylpropanoyl-CoA = N(6)-[(R)-S(8)-2-methylpropanoyldihydrolipoyl]-L-lysyl-[protein] + CoACOFACTOR Binds 1 lipoyl cofactor covalently.SUBUNIT Forms a 24-polypeptide structural core with octahedral symmetry that represents the E2 component of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. The BCKDH complex is composed of three major building blocks E1, E2 and E3. It is organized around E2, a 24-meric cubic core composed of DBT, to which are associated 6 to 12 copies of E1, and approximately 6 copies of the dehydrogenase E3, a DLD dimer (By similarity) (PubMed:22291014). Interacts with PPM1K with a 24:1 stoichiometry; the N-terminal region (residues 49-61) of PPM1K and C-terminal linker of the lipoyl domain of DBT/E2 (residues 145-160) are critical for this interaction whereas the lipoyl prosthetic group is dispensable. This interaction requires colocalization in mitochondria (PubMed:19411760, PubMed:22291014, PubMed:22589535). PPM1K competes with BCKDK for binding to DBT; this interaction is modulated by branched-chain alpha-keto acids (BCKAs). At steady state, BCKDH holoenzyme preferentially binds BCKDK and BCKDHA is phosphorylated. In response to high levels of BCKAs, BCKDK is replaced by PPM1K leading to BCKDHA dephosphorylation (PubMed:22589535, PubMed:37558654).INTERACTION 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.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the 2-oxoacid dehydrogenase family.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Truncated N-terminus.
databaseName
UniProt
dbId
60856
description
-
recommendedName: fullName evidence="28"Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial ecNumber evidence="1"2.3.1.168 alternativeName: fullName evidence="24"52 kDa mitochondrial autoantigen of primary biliary cirrhosis alternativeName: fullName evidence="26 27"Branched chain 2-oxo-acid dehydrogenase complex component E2 shortName evidence="26 27"BCOADC-E2 alternativeName: Branched-chain alpha-keto acid dehydrogenase complex component E2 shortName: BCKAD-E2 shortName: BCKADE2 shortName evidence="25"BCKDH-E2 alternativeName: Dihydrolipoamide acetyltransferase component of branched-chain alpha-keto acid dehydrogenase complex alternativeName: Dihydrolipoamide branched chain transacylase alternativeName: Dihydrolipoyllysine-residue (2-methylpropanoyl)transferase
displayName
UniProt:P11182 DBT
identifier
P11182
isSequenceChanged
false
keyword
-
3D-structure
-
Acetylation
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Acyltransferase
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Direct protein sequencing
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Disease variant
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Lipoyl
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Maple syrup urine disease
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Mitochondrion
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Phosphoprotein
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Proteomics identification
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Reference proteome
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Transferase
-
Transit peptide
moleculeType
Protein
otherIdentifier
-
11731509_x_at
-
11731510_at
-
11731511_s_at
-
11751182_a_at
-
11752357_a_at
-
11762117_at
-
1629
-
16690103
-
205369_3p_x_at
-
205369_PM_x_at
-
205369_x_at
-
205370_PM_x_at
-
205370_x_at
-
205371_PM_s_at
-
205371_s_at
-
211196_3p_at
-
211196_PM_at
-
211196_at
-
231919_PM_at
-
231919_at
-
2425203
-
2425205
-
2425207
-
2425209
-
2425210
-
2425211
-
2425213
-
2425214
-
2425215
-
2425216
-
2425217
-
2425218
-
2425219
-
2425220
-
2425221
-
2425222
-
2425226
-
2425231
-
2425233
-
2425234
-
2425237
-
2425238
-
2425239
-
2425240
-
2425241
-
2425242
-
2425243
-
244687_PM_at
-
244687_at
-
37862_at
-
51919_at
-
7918008
-
86425_at
-
A_23_P74022
-
A_24_P28524
-
A_32_P50005
-
A_33_P3291594
-
A_33_P3308949
-
GE59930
-
GE85471
-
GO:0005515
-
GO:0005739
-
GO:0005759
-
GO:0005829
-
GO:0005856
-
GO:0006520
-
GO:0009083
-
GO:0015630
-
GO:0016740
-
GO:0016746
-
GO:0016747
-
GO:0031625
-
GO:0042645
-
GO:0043754
-
GO:0120552
-
GO:0160157
-
HMNXSV003008442
-
HMNXSV003021704
-
Hs.199210.0.A1_3p_at
-
Hs.257043.0.S1_3p_at
-
ILMN_1714990
-
ILMN_1887403
-
M19301_at
-
M27093_s_at
-
PH_hs_0013509
-
PH_hs_0021360
-
PH_hs_0027858
-
TC01002918.hg
-
X66785_at
-
g179353_3p_a_at
-
g179353_3p_x_at
-
g186635_3p_a_at
-
g186635_3p_at
-
g186635_3p_x_at
-
g4503264_3p_at
-
g736674_3p_a_at
schemaClass
ReferenceGeneProduct
sequenceLength
482
stId
uniprot:P11182