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Protein

2-oxoisovalerate dehydrogenase subunit beta, mitochondrial

Gene

BCKDHB

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).

Catalytic activityi

3-methyl-2-oxobutanoate + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine = [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] S-(2-methylpropanoyl)dihydrolipoyllysine + CO2.

GO - Molecular functioni

  • 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity Source: ProtInc
  • alpha-ketoacid dehydrogenase activity Source: Ensembl
  • carboxy-lyase activity Source: HGNC

GO - Biological processi

  • branched-chain amino acid catabolic process Source: HGNC
  • glyoxylate metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-12006.
ZFISH:MONOMER-12006.
ReactomeiR-HSA-389661. Glyoxylate metabolism and glycine degradation.
R-HSA-70895. Branched-chain amino acid catabolism.
SABIO-RKP21953.

Names & Taxonomyi

Protein namesi
Recommended name:
2-oxoisovalerate dehydrogenase subunit beta, mitochondrial (EC:1.2.4.4)
Alternative name(s):
Branched-chain alpha-keto acid dehydrogenase E1 component beta chain
Short name:
BCKDE1B
Short name:
BCKDH E1-beta
Gene namesi
Name:BCKDHB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:987. BCKDHB.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial alpha-ketoglutarate dehydrogenase complex Source: HGNC
  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Maple syrup urine disease 1B (MSUD1B)3 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_068348170R → H in MSUD1B. 1 PublicationCorresponds to variant rs371518124dbSNPEnsembl.1
Natural variantiVAR_024851183R → P in MSUD1B. 1 PublicationCorresponds to variant rs28934895dbSNPEnsembl.1
Natural variantiVAR_004974206H → R in MSUD1B. 1 Publication1
Natural variantiVAR_024852278G → S in MSUD1B. 1 PublicationCorresponds to variant rs386834233dbSNPEnsembl.1
Natural variantiVAR_068349346Q → R in MSUD1B. 1 Publication1

Keywords - Diseasei

Disease mutation, Maple syrup urine disease

Organism-specific databases

DisGeNETi594.
MalaCardsiBCKDHB.
MIMi248600. phenotype.
OpenTargetsiENSG00000083123.
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.
PharmGKBiPA25298.

Polymorphism and mutation databases

BioMutaiBCKDHB.
DMDMi129034.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 50MitochondrionCombined sourcesAdd BLAST50
ChainiPRO_000002047051 – 3922-oxoisovalerate dehydrogenase subunit beta, mitochondrialAdd BLAST342

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei232N6-acetyllysineBy similarity1
Modified residuei241N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP21953.
PaxDbiP21953.
PeptideAtlasiP21953.
PRIDEiP21953.
TopDownProteomicsiP21953-1. [P21953-1]

2D gel databases

REPRODUCTION-2DPAGEIPI00011276.

PTM databases

iPTMnetiP21953.
PhosphoSitePlusiP21953.

Expressioni

Gene expression databases

BgeeiENSG00000083123.
CleanExiHS_BCKDHB.
ExpressionAtlasiP21953. baseline and differential.
GenevisibleiP21953. HS.

Organism-specific databases

HPAiHPA031580.

Interactioni

Subunit structurei

Heterotetramer of 2 alpha and 2 beta chains.

Binary interactionsi

WithEntry#Exp.IntActNotes
BCKDHAP1269414EBI-1029067,EBI-1029053

Protein-protein interaction databases

BioGridi107066. 12 interactors.
DIPiDIP-6147N.
IntActiP21953. 4 interactors.
MINTiMINT-271857.
STRINGi9606.ENSP00000318351.

Structurei

Secondary structure

1392
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi68 – 71Combined sources4
Helixi73 – 87Combined sources15
Beta strandi92 – 95Combined sources4
Turni96 – 101Combined sources6
Turni106 – 109Combined sources4
Helixi110 – 114Combined sources5
Turni116 – 118Combined sources3
Beta strandi119 – 121Combined sources3
Helixi126 – 138Combined sources13
Beta strandi143 – 146Combined sources4
Helixi150 – 152Combined sources3
Helixi154 – 156Combined sources3
Helixi157 – 161Combined sources5
Helixi164 – 166Combined sources3
Helixi167 – 170Combined sources4
Turni171 – 173Combined sources3
Beta strandi180 – 187Combined sources8
Helixi193 – 195Combined sources3
Helixi201 – 205Combined sources5
Beta strandi211 – 213Combined sources3
Helixi218 – 230Combined sources13
Beta strandi231 – 233Combined sources3
Beta strandi235 – 240Combined sources6
Helixi241 – 243Combined sources3
Turni244 – 246Combined sources3
Beta strandi249 – 254Combined sources6
Beta strandi264 – 267Combined sources4
Beta strandi270 – 276Combined sources7
Helixi280 – 295Combined sources16
Beta strandi299 – 303Combined sources5
Beta strandi306 – 309Combined sources4
Helixi312 – 322Combined sources11
Beta strandi325 – 333Combined sources9
Helixi337 – 349Combined sources13
Helixi350 – 352Combined sources3
Beta strandi358 – 362Combined sources5
Helixi372 – 375Combined sources4
Helixi379 – 390Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DTWX-ray2.70B51-392[»]
1OLSX-ray1.85B51-392[»]
1OLUX-ray1.90B51-392[»]
1OLXX-ray2.25B51-392[»]
1U5BX-ray1.83B51-392[»]
1V11X-ray1.95B51-392[»]
1V16X-ray1.90B51-392[»]
1V1MX-ray2.00B51-392[»]
1V1RX-ray1.80B51-392[»]
1WCIX-ray1.84B51-392[»]
1X7WX-ray1.73B51-392[»]
1X7XX-ray2.10B51-392[»]
1X7YX-ray1.57B51-392[»]
1X7ZX-ray1.72B51-392[»]
1X80X-ray2.00B51-392[»]
2BEUX-ray1.89B51-392[»]
2BEVX-ray1.80B51-392[»]
2BEWX-ray1.79B51-392[»]
2BFBX-ray1.77B51-392[»]
2BFCX-ray1.64B51-392[»]
2BFDX-ray1.39B51-392[»]
2BFEX-ray1.69B51-392[»]
2BFFX-ray1.46B51-392[»]
2J9FX-ray1.88B/D51-392[»]
ProteinModelPortaliP21953.
SMRiP21953.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21953.

Family & Domainsi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0525. Eukaryota.
COG0022. LUCA.
GeneTreeiENSGT00530000063423.
HOGENOMiHOG000281451.
HOVERGENiHBG108210.
InParanoidiP21953.
KOiK00167.
OMAiLAWGAQM.
OrthoDBiEOG091G0B9T.
PhylomeDBiP21953.
TreeFamiTF105947.

Family and domain databases

Gene3Di3.40.50.920. 1 hit.
3.40.50.970. 1 hit.
InterProiIPR029061. THDP-binding.
IPR009014. Transketo_C/PFOR_II.
IPR005475. Transketolase-like_Pyr-bd.
IPR033248. Transketolase_C.
IPR033247. Transketolase_fam.
[Graphical view]
PANTHERiPTHR11624. PTHR11624. 1 hit.
PfamiPF02779. Transket_pyr. 1 hit.
PF02780. Transketolase_C. 1 hit.
[Graphical view]
SMARTiSM00861. Transket_pyr. 1 hit.
[Graphical view]
SUPFAMiSSF52518. SSF52518. 1 hit.
SSF52922. SSF52922. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P21953-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAVVAAAAGW LLRLRAAGAE GHWRRLPGAG LARGFLHPAA TVEDAAQRRQ
60 70 80 90 100
VAHFTFQPDP EPREYGQTQK MNLFQSVTSA LDNSLAKDPT AVIFGEDVAF
110 120 130 140 150
GGVFRCTVGL RDKYGKDRVF NTPLCEQGIV GFGIGIAVTG ATAIAEIQFA
160 170 180 190 200
DYIFPAFDQI VNEAAKYRYR SGDLFNCGSL TIRSPWGCVG HGALYHSQSP
210 220 230 240 250
EAFFAHCPGI KVVIPRSPFQ AKGLLLSCIE DKNPCIFFEP KILYRAAAEE
260 270 280 290 300
VPIEPYNIPL SQAEVIQEGS DVTLVAWGTQ VHVIREVASM AKEKLGVSCE
310 320 330 340 350
VIDLRTIIPW DVDTICKSVI KTGRLLISHE APLTGGFASE ISSTVQEECF
360 370 380 390
LNLEAPISRV CGYDTPFPHI FEPFYIPDKW KCYDALRKMI NY
Length:392
Mass (Da):43,122
Last modified:August 1, 1992 - v2
Checksum:iD78097834D063BB7
GO
Isoform 2 (identifier: P21953-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     212-218: VVIPRSP → IKVISLS
     219-392: Missing.

Note: No experimental confirmation available.
Show »
Length:218
Mass (Da):23,550
Checksum:iFF30CBDA08FEF0F7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20 – 23EGHW → RLPP (PubMed:2335211).Curated4
Sequence conflicti322T → S in CAA36685 (PubMed:2335211).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05043741T → I.Corresponds to variant rs35470366dbSNPEnsembl.1
Natural variantiVAR_068348170R → H in MSUD1B. 1 PublicationCorresponds to variant rs371518124dbSNPEnsembl.1
Natural variantiVAR_024851183R → P in MSUD1B. 1 PublicationCorresponds to variant rs28934895dbSNPEnsembl.1
Natural variantiVAR_004974206H → R in MSUD1B. 1 Publication1
Natural variantiVAR_024852278G → S in MSUD1B. 1 PublicationCorresponds to variant rs386834233dbSNPEnsembl.1
Natural variantiVAR_068349346Q → R in MSUD1B. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056370212 – 218VVIPRSP → IKVISLS in isoform 2. 1 Publication7
Alternative sequenceiVSP_056371219 – 392Missing in isoform 2. 1 PublicationAdd BLAST174

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55575 mRNA. Translation: AAA51812.1.
D90391 Genomic DNA. Translation: BAA14389.1.
AK289977 mRNA. Translation: BAF82666.1.
BT020063 mRNA. Translation: AAV38866.1.
AL049696, AL391595 Genomic DNA. Translation: CAC36881.2.
AL391595, AL049696 Genomic DNA. Translation: CAI15049.1.
CH471051 Genomic DNA. Translation: EAW48696.1.
CH471051 Genomic DNA. Translation: EAW48697.1.
CH471051 Genomic DNA. Translation: EAW48698.1.
BC034481 mRNA. Translation: AAH34481.1.
BC040139 mRNA. Translation: AAH40139.1.
U50708 mRNA. Translation: AAB16763.1.
X52446 mRNA. Translation: CAA36685.1.
CCDSiCCDS4994.1. [P21953-1]
PIRiA37157.
RefSeqiNP_000047.1. NM_000056.4. [P21953-1]
NP_001305904.1. NM_001318975.1.
NP_898871.1. NM_183050.3. [P21953-1]
UniGeneiHs.654441.

Genome annotation databases

EnsembliENST00000320393; ENSP00000318351; ENSG00000083123. [P21953-1]
ENST00000356489; ENSP00000348880; ENSG00000083123. [P21953-1]
ENST00000369760; ENSP00000358775; ENSG00000083123. [P21953-2]
GeneIDi594.
KEGGihsa:594.
UCSCiuc003pjd.3. human. [P21953-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55575 mRNA. Translation: AAA51812.1.
D90391 Genomic DNA. Translation: BAA14389.1.
AK289977 mRNA. Translation: BAF82666.1.
BT020063 mRNA. Translation: AAV38866.1.
AL049696, AL391595 Genomic DNA. Translation: CAC36881.2.
AL391595, AL049696 Genomic DNA. Translation: CAI15049.1.
CH471051 Genomic DNA. Translation: EAW48696.1.
CH471051 Genomic DNA. Translation: EAW48697.1.
CH471051 Genomic DNA. Translation: EAW48698.1.
BC034481 mRNA. Translation: AAH34481.1.
BC040139 mRNA. Translation: AAH40139.1.
U50708 mRNA. Translation: AAB16763.1.
X52446 mRNA. Translation: CAA36685.1.
CCDSiCCDS4994.1. [P21953-1]
PIRiA37157.
RefSeqiNP_000047.1. NM_000056.4. [P21953-1]
NP_001305904.1. NM_001318975.1.
NP_898871.1. NM_183050.3. [P21953-1]
UniGeneiHs.654441.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DTWX-ray2.70B51-392[»]
1OLSX-ray1.85B51-392[»]
1OLUX-ray1.90B51-392[»]
1OLXX-ray2.25B51-392[»]
1U5BX-ray1.83B51-392[»]
1V11X-ray1.95B51-392[»]
1V16X-ray1.90B51-392[»]
1V1MX-ray2.00B51-392[»]
1V1RX-ray1.80B51-392[»]
1WCIX-ray1.84B51-392[»]
1X7WX-ray1.73B51-392[»]
1X7XX-ray2.10B51-392[»]
1X7YX-ray1.57B51-392[»]
1X7ZX-ray1.72B51-392[»]
1X80X-ray2.00B51-392[»]
2BEUX-ray1.89B51-392[»]
2BEVX-ray1.80B51-392[»]
2BEWX-ray1.79B51-392[»]
2BFBX-ray1.77B51-392[»]
2BFCX-ray1.64B51-392[»]
2BFDX-ray1.39B51-392[»]
2BFEX-ray1.69B51-392[»]
2BFFX-ray1.46B51-392[»]
2J9FX-ray1.88B/D51-392[»]
ProteinModelPortaliP21953.
SMRiP21953.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107066. 12 interactors.
DIPiDIP-6147N.
IntActiP21953. 4 interactors.
MINTiMINT-271857.
STRINGi9606.ENSP00000318351.

PTM databases

iPTMnetiP21953.
PhosphoSitePlusiP21953.

Polymorphism and mutation databases

BioMutaiBCKDHB.
DMDMi129034.

2D gel databases

REPRODUCTION-2DPAGEIPI00011276.

Proteomic databases

EPDiP21953.
PaxDbiP21953.
PeptideAtlasiP21953.
PRIDEiP21953.
TopDownProteomicsiP21953-1. [P21953-1]

Protocols and materials databases

DNASUi594.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000320393; ENSP00000318351; ENSG00000083123. [P21953-1]
ENST00000356489; ENSP00000348880; ENSG00000083123. [P21953-1]
ENST00000369760; ENSP00000358775; ENSG00000083123. [P21953-2]
GeneIDi594.
KEGGihsa:594.
UCSCiuc003pjd.3. human. [P21953-1]

Organism-specific databases

CTDi594.
DisGeNETi594.
GeneCardsiBCKDHB.
GeneReviewsiBCKDHB.
HGNCiHGNC:987. BCKDHB.
HPAiHPA031580.
MalaCardsiBCKDHB.
MIMi248600. phenotype.
248611. gene.
neXtProtiNX_P21953.
OpenTargetsiENSG00000083123.
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.
PharmGKBiPA25298.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0525. Eukaryota.
COG0022. LUCA.
GeneTreeiENSGT00530000063423.
HOGENOMiHOG000281451.
HOVERGENiHBG108210.
InParanoidiP21953.
KOiK00167.
OMAiLAWGAQM.
OrthoDBiEOG091G0B9T.
PhylomeDBiP21953.
TreeFamiTF105947.

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-12006.
ZFISH:MONOMER-12006.
ReactomeiR-HSA-389661. Glyoxylate metabolism and glycine degradation.
R-HSA-70895. Branched-chain amino acid catabolism.
SABIO-RKP21953.

Miscellaneous databases

ChiTaRSiBCKDHB. human.
EvolutionaryTraceiP21953.
GeneWikiiBCKDHB.
GenomeRNAii594.
PROiP21953.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000083123.
CleanExiHS_BCKDHB.
ExpressionAtlasiP21953. baseline and differential.
GenevisibleiP21953. HS.

Family and domain databases

Gene3Di3.40.50.920. 1 hit.
3.40.50.970. 1 hit.
InterProiIPR029061. THDP-binding.
IPR009014. Transketo_C/PFOR_II.
IPR005475. Transketolase-like_Pyr-bd.
IPR033248. Transketolase_C.
IPR033247. Transketolase_fam.
[Graphical view]
PANTHERiPTHR11624. PTHR11624. 1 hit.
PfamiPF02779. Transket_pyr. 1 hit.
PF02780. Transketolase_C. 1 hit.
[Graphical view]
SMARTiSM00861. Transket_pyr. 1 hit.
[Graphical view]
SUPFAMiSSF52518. SSF52518. 1 hit.
SSF52922. SSF52922. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiODBB_HUMAN
AccessioniPrimary (citable) accession number: P21953
Secondary accession number(s): Q5T2J3, Q9BQL0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1992
Last modified: November 30, 2016
This is version 183 of the entry and version 2 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 6
    Human chromosome 6: 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

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.