ID   Q3U3J1_MOUSE            Unreviewed;       446 AA.
AC   Q3U3J1;
DT   11-OCT-2005, integrated into UniProtKB/TrEMBL.
DT   11-OCT-2005, sequence version 1.
DT   27-MAR-2024, entry version 145.
DE   RecName: Full=2-oxoisovalerate dehydrogenase subunit alpha {ECO:0000256|RuleBase:RU365014};
DE            EC=1.2.4.4 {ECO:0000256|RuleBase:RU365014};
DE   AltName: Full=Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain {ECO:0000256|RuleBase:RU365014};
GN   Name=Bckdha {ECO:0000313|Ensembl:ENSMUSP00000071292.7,
GN   ECO:0000313|MGI:MGI:107701};
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 {ECO:0000313|EMBL:BAE32795.1};
RN   [1] {ECO:0000313|EMBL:BAE32795.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=NOD {ECO:0000313|EMBL:BAE32795.1};
RX   PubMed=10349636; DOI=10.1016/S0076-6879(99)03004-9;
RA   Carninci P., Hayashizaki Y.;
RT   "High-efficiency full-length cDNA cloning.";
RL   Methods Enzymol. 303:19-44(1999).
RN   [2] {ECO:0000313|EMBL:BAE32795.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=NOD {ECO:0000313|EMBL:BAE32795.1};
RX   PubMed=11042159; DOI=10.1101/gr.145100;
RA   Carninci P., Shibata Y., Hayatsu N., Sugahara Y., Shibata K., Itoh M.,
RA   Konno H., Okazaki Y., Muramatsu M., Hayashizaki Y.;
RT   "Normalization and subtraction of cap-trapper-selected cDNAs to prepare
RT   full-length cDNA libraries for rapid discovery of new genes.";
RL   Genome Res. 10:1617-1630(2000).
RN   [3] {ECO:0000313|EMBL:BAE32795.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=NOD {ECO:0000313|EMBL:BAE32795.1};
RX   PubMed=11076861; DOI=10.1101/gr.152600;
RA   Shibata K., Itoh M., Aizawa K., Nagaoka S., Sasaki N., Carninci P.,
RA   Konno H., Akiyama J., Nishi K., Kitsunai T., Tashiro H., Itoh M., Sumi N.,
RA   Ishii Y., Nakamura S., Hazama M., Nishine T., Harada A., Yamamoto R.,
RA   Matsumoto H., Sakaguchi S., Ikegami T., Kashiwagi K., Fujiwake S.,
RA   Inoue K., Togawa Y., Izawa M., Ohara E., Watahiki M., Yoneda Y.,
RA   Ishikawa T., Ozawa K., Tanaka T., Matsuura S., Kawai J., Okazaki Y.,
RA   Muramatsu M., Inoue Y., Kira A., Hayashizaki Y.;
RT   "RIKEN integrated sequence analysis (RISA) system--384-format sequencing
RT   pipeline with 384 multicapillary sequencer.";
RL   Genome Res. 10:1757-1771(2000).
RN   [4] {ECO:0000313|EMBL:BAE32795.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=NOD {ECO:0000313|EMBL:BAE32795.1};
RX   PubMed=11217851; DOI=10.1038/35055500;
RG   The RIKEN Genome Exploration Research Group Phase II Team and the FANTOM Consortium;
RT   "Functional annotation of a full-length mouse cDNA collection.";
RL   Nature 409:685-690(2001).
RN   [5] {ECO:0000313|EMBL:BAE32795.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=NOD {ECO:0000313|EMBL:BAE32795.1};
RX   PubMed=12466851; DOI=10.1038/nature01266;
RG   The FANTOM Consortium and the RIKEN Genome Exploration Research Group Phase I and II Team;
RT   "Analysis of the mouse transcriptome based on functional annotation of
RT   60,770 full-length cDNAs.";
RL   Nature 420:563-573(2002).
RN   [6] {ECO:0000313|EMBL:BAE32795.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=NOD {ECO:0000313|EMBL:BAE32795.1};
RA   Arakawa T., Carninci P., Fukuda S., Hashizume W., Hayashida K., Hori F.,
RA   Iida J., Imamura K., Imotani K., Itoh M., Kanagawa S., Kawai J., Kojima M.,
RA   Konno H., Murata M., Nakamura M., Ninomiya N., Nishiyori H., Nomura K.,
RA   Ohno M., Sakazume N., Sano H., Sasaki D., Shibata K., Shiraki T.,
RA   Tagami M., Tagami Y., Waki K., Watahiki A., Muramatsu M., Hayashizaki Y.;
RL   Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN   [7] {ECO:0000313|EMBL:BAE32795.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=NOD {ECO:0000313|EMBL:BAE32795.1};
RG   The FANTOM Consortium;
RG   Riken Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group);
RT   "The Transcriptional Landscape of the Mammalian Genome.";
RL   Science 309:1559-1563(2005).
RN   [8] {ECO:0000313|EMBL:BAE32795.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=NOD {ECO:0000313|EMBL:BAE32795.1};
RX   PubMed=16141073; DOI=10.1126/science.1112009;
RG   RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group) and the FANTOM Consortium;
RT   "Antisense Transcription in the Mammalian Transcriptome.";
RL   Science 309:1564-1566(2005).
RN   [9] {ECO:0007829|PubMed:17208939}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [10] {ECO:0007829|PubMed:17242355}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [11] {ECO:0007829|PubMed:19144319}
RP   IDENTIFICATION BY 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   [12] {ECO:0000313|Ensembl:ENSMUSP00000071292.7, ECO:0000313|Proteomes:UP000000589}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J {ECO:0000313|Ensembl:ENSMUSP00000071292.7,
RC   ECO:0000313|Proteomes:UP000000589};
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [13] {ECO:0007829|PubMed:21183079}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [14] {ECO:0007829|PubMed:23806337}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [15] {ECO:0007829|PubMed:23576753}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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).
RN   [16] {ECO:0000313|Ensembl:ENSMUSP00000071292.7}
RP   IDENTIFICATION.
RC   STRAIN=C57BL/6J {ECO:0000313|Ensembl:ENSMUSP00000071292.7};
RG   Ensembl;
RL   Submitted (NOV-2023) to UniProtKB.
CC   -!- FUNCTION: Together with BCKDHB forms the heterotetrameric E1 subunit of
CC       the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD)
CC       complex. The BCKD complex catalyzes the multi-step oxidative
CC       decarboxylation of alpha-ketoacids derived from the branched-chain
CC       amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA
CC       which is subsequently utilized to produce energy. The E1 subunit
CC       catalyzes the first step with the decarboxylation of the alpha-ketoacid
CC       forming an enzyme-product intermediate. A reductive acylation mediated
CC       by the lipoylamide cofactor of E2 extracts the acyl group from the E1
CC       active site for the next step of the reaction.
CC       {ECO:0000256|ARBA:ARBA00037052, ECO:0000256|RuleBase:RU365014}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3-methyl-2-oxobutanoate + H(+) + N(6)-[(R)-lipoyl]-L-lysyl-
CC         [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] = CO2 +
CC         N(6)-[(R)-S(8)-2-methylpropanoyldihydrolipoyl]-L-lysyl-
CC         [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase];
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         Evidence={ECO:0000256|ARBA:ARBA00043720};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13458;
CC         Evidence={ECO:0000256|ARBA:ARBA00043720};
CC   -!- COFACTOR:
CC       Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC         Evidence={ECO:0000256|RuleBase:RU365014};
CC   -!- SIMILARITY: Belongs to the BCKDHA family.
CC       {ECO:0000256|ARBA:ARBA00008646, ECO:0000256|RuleBase:RU365014}.
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DR   EMBL; AK154734; BAE32795.1; -; mRNA.
DR   RefSeq; NP_031559.3; NM_007533.5.
DR   ProteomicsDB; 341125; -.
DR   DNASU; 12039; -.
DR   Ensembl; ENSMUST00000071329.8; ENSMUSP00000071292.7; ENSMUSG00000060376.8.
DR   GeneID; 12039; -.
DR   UCSC; uc009fth.2; mouse.
DR   AGR; MGI:107701; -.
DR   CTD; 593; -.
DR   MGI; MGI:107701; Bckdha.
DR   VEuPathDB; HostDB:ENSMUSG00000060376; -.
DR   GeneTree; ENSGT00530000063174; -.
DR   HOGENOM; CLU_029393_1_2_1; -.
DR   OMA; EMFEGVY; -.
DR   OrthoDB; 952at2759; -.
DR   TreeFam; TF300863; -.
DR   BioGRID-ORCS; 12039; 2 hits in 79 CRISPR screens.
DR   ChiTaRS; Bckdha; mouse.
DR   Proteomes; UP000000589; Chromosome 7.
DR   Bgee; ENSMUSG00000060376; Expressed in right kidney and 260 other cell types or tissues.
DR   GO; GO:0005947; C:mitochondrial alpha-ketoglutarate dehydrogenase complex; IEA:Ensembl.
DR   GO; GO:0003863; F:3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity; IEA:UniProtKB-EC.
DR   GO; GO:0009083; P:branched-chain amino acid catabolic process; IEA:Ensembl.
DR   CDD; cd02000; TPP_E1_PDC_ADC_BCADC; 1.
DR   Gene3D; 3.40.50.970; -; 1.
DR   InterPro; IPR001017; DH_E1.
DR   InterPro; IPR029061; THDP-binding.
DR   PANTHER; PTHR43380; 2-OXOISOVALERATE DEHYDROGENASE SUBUNIT ALPHA, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR43380:SF1; 2-OXOISOVALERATE DEHYDROGENASE SUBUNIT ALPHA, MITOCHONDRIAL; 1.
DR   Pfam; PF00676; E1_dh; 1.
DR   SUPFAM; SSF52518; Thiamin diphosphate-binding fold (THDP-binding); 1.
PE   1: Evidence at protein level;
KW   Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW   ECO:0000256|RuleBase:RU365014}; Potassium {ECO:0000256|ARBA:ARBA00022958};
KW   Proteomics identification {ECO:0007829|EPD:Q3U3J1,
KW   ECO:0007829|MaxQB:Q3U3J1};
KW   Reference proteome {ECO:0000313|Proteomes:UP000000589};
KW   Thiamine pyrophosphate {ECO:0000256|RuleBase:RU365014};
KW   Transit peptide {ECO:0000256|ARBA:ARBA00022946}.
FT   DOMAIN          107..406
FT                   /note="Dehydrogenase E1 component"
FT                   /evidence="ECO:0000259|Pfam:PF00676"
FT   REGION          34..54
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        35..50
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   446 AA;  50773 MW;  110D5F3FA8A3108D CRC64;
     MAIVMSAAKI WRPSRGLRQA ALLLLGRSGV RGLARSHPSR QQQQQFPSLD DKPQFPGASA
     EFVDKLEFIQ PNVISGIPIY RVMDRQGQII NPSEDPHLPQ EEVLKFYRSM TLLNTMDRIL
     YESQRQGRIS FYMTNYGEEG THVGSAAALE RTDLVFGQYR EAGVLMYRDY PLELFMSQCY
     GNVNDPGKGR QMPVHYGCKE RHFVTISSPL ATQIPQAVGA AYAAKRANAN RIVICYFGEG
     AASEGDAHAG FNFAATLECP IIFFCRNNGY AISTPTSEQY RGDGIAARGP GYGIMSIRVD
     GNDVFAVYNA TKEARRRAVA ENQPFLIEAM TYRIGHHSTS DDSSAYRSVD EVNYWDKQDH
     PISRLRQYLL NQGWWDEEQE KAWRKQSRKK VMEAFEQAER KLKPNPSLLF SDVYQEMPAQ
     LRRQQESLAR HLQTYGEHYP LDHFDK
//