ODBA_MOUSE
ID ODBA_MOUSE Reviewed; 442 AA.
AC P50136;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial;
DE EC=1.2.4.4;
DE AltName: Full=Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain;
DE Short=BCKDE1A;
DE Short=BCKDH E1-alpha;
DE Flags: Precursor;
GN Name=Bckdha;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=8761456; DOI=10.1042/bj3180085;
RA Costeas P.A., Chinsky J.M.;
RT "Effects of insulin on the regulation of branched-chain alpha-keto acid
RT dehydrogenase E1 alpha subunit gene expression.";
RL Biochem. J. 318:85-92(1996).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17208939; DOI=10.1074/mcp.m600218-mcp200;
RA Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y.;
RT "Mitochondrial phosphoproteome revealed by an improved IMAC method and
RT MS/MS/MS.";
RL Mol. Cell. Proteomics 6:669-676(2007).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-334, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-334; THR-335; SER-336 AND
RP SER-344, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-353 AND LYS-377, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-353, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: The branched-chain alpha-keto dehydrogenase complex catalyzes
CC the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It
CC contains multiple copies of three enzymatic components: branched-chain
CC alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and
CC lipoamide dehydrogenase (E3).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-lipoyl-L-lysyl-[dihydrolipoyllysine-residue (2-
CC methylpropanoyl)transferase] + 3-methyl-2-oxobutanoate + H(+) = (R)-
CC N(6)-(S(8)-2-methylpropanoyldihydrolipoyl)-L-lysyl-
CC [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] + CO2;
CC Xref=Rhea:RHEA:13457, Rhea:RHEA-COMP:10488, Rhea:RHEA-COMP:10489,
CC ChEBI:CHEBI:11851, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:83099, ChEBI:CHEBI:83142; EC=1.2.4.4;
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC -!- SUBUNIT: Heterotetramer of alpha and beta chains. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- MISCELLANEOUS: Bound potassium ions stabilize the protein structure.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the BCKDHA family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L47335; AAB38422.1; -; mRNA.
DR PIR; S71881; S71881.
DR AlphaFoldDB; P50136; -.
DR SMR; P50136; -.
DR IntAct; P50136; 2.
DR MINT; P50136; -.
DR STRING; 10090.ENSMUSP00000071292; -.
DR iPTMnet; P50136; -.
DR PhosphoSitePlus; P50136; -.
DR SWISS-2DPAGE; P50136; -.
DR EPD; P50136; -.
DR jPOST; P50136; -.
DR MaxQB; P50136; -.
DR PaxDb; P50136; -.
DR PeptideAtlas; P50136; -.
DR PRIDE; P50136; -.
DR ProteomicsDB; 293919; -.
DR MGI; MGI:107701; Bckdha.
DR eggNOG; KOG1182; Eukaryota.
DR InParanoid; P50136; -.
DR PhylomeDB; P50136; -.
DR Reactome; R-MMU-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-MMU-70895; Branched-chain amino acid catabolism.
DR ChiTaRS; Bckdha; mouse.
DR PRO; PR:P50136; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P50136; protein.
DR GO; GO:0005947; C:mitochondrial alpha-ketoglutarate dehydrogenase complex; ISS:HGNC-UCL.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0003863; F:3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity; ISS:HGNC-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0009083; P:branched-chain amino acid catabolic process; ISS:HGNC-UCL.
DR InterPro; IPR034616; BCKDH_E1-a.
DR InterPro; IPR001017; DH_E1.
DR InterPro; IPR029061; THDP-binding.
DR PANTHER; PTHR43380:SF1; PTHR43380:SF1; 1.
DR Pfam; PF00676; E1_dh; 1.
DR SUPFAM; SSF52518; SSF52518; 1.
PE 1: Evidence at protein level;
KW Acetylation; Metal-binding; Mitochondrion; Oxidoreductase; Phosphoprotein;
KW Potassium; Reference proteome; Thiamine pyrophosphate; Transit peptide.
FT TRANSIT 1..42
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 43..442
FT /note="2-oxoisovalerate dehydrogenase subunit alpha,
FT mitochondrial"
FT /id="PRO_0000020467"
FT REGION 30..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..46
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 154..156
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 203
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250"
FT BINDING 208
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250"
FT BINDING 209
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 335
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 336
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 353
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 353
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 377
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
SQ SEQUENCE 442 AA; 50371 MW; 3388213D88BC7C92 CRC64;
MSAAKIWRPS RGLRQAALLL LGRSGVRGLA RSHPSRQQQQ QFPSLDDKPQ FPGASAEFVD
KLEFIQPNVI SGIPIYRVMD RQGQIINPSE DPHLPQEEVL KFYRSMTLLN TMDRILYESQ
REGRISFYMT NYGEEGTHVG SAAALERTDL VFGQYREAGV LMYRDYPLEL FMSQCYGNVN
DPGKGRQMPV HYGCKERHFV TISSPLATQI PQAVGAAYAA KRANANRIVI CYFGEGAASE
GDAHAGFNFA ATLECPIIFF CRNNGYAIST PTSEQYRGDG IAARGPGYGI KSIRVDGNDV
FAVYNATKEA RRRAVAENQP FLIEAMTYRI GHHSTSDDSS AYRSVDEVNY WDKQDHPISR
LRQYLLNQGW WDEEQEKAWR KQSRKKVMEA FEQAERKLKP NPSLLFSDVY QEMPAQLRRQ
QESLARHLQT YGEHYPLDHF EK
