BCKD_RAT
ID BCKD_RAT Reviewed; 412 AA.
AC Q00972; Q64552;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial;
DE EC=2.7.11.4 {ECO:0000269|PubMed:1377677, ECO:0000269|PubMed:7649998};
DE AltName: Full=Branched-chain alpha-ketoacid dehydrogenase kinase;
DE Short=BCKD-kinase;
DE Short=BCKDHKIN;
DE Flags: Precursor;
GN Name=Bckdk;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 31-67; 93-100; 254-260 AND
RP 328-343, TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RC TISSUE=Heart;
RX PubMed=1377677; DOI=10.1016/s0021-9258(18)42179-5;
RA Popov K.M., Zhao Y., Shimomura Y., Kuntz M.J., Harris R.A.;
RT "Branched-chain alpha-ketoacid dehydrogenase kinase. Molecular cloning,
RT expression, and sequence similarity with histidine protein kinases.";
RL J. Biol. Chem. 267:13127-13130(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=1496922; DOI=10.1016/0065-2571(92)90022-r;
RA Harris R.A., Popov K.M., Shimomura Y., Zhao Y., Jaskiewicz J., Nanaumi N.,
RA Suzuki M.;
RT "Purification, characterization, regulation and molecular cloning of
RT mitochondrial protein kinases.";
RL Adv. Enzyme Regul. 32:267-284(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 31-412, SEQUENCE REVISION TO 110-124 AND 222,
RP PHOSPHORYLATION AT SER-31, AND CATALYTIC ACTIVITY.
RC TISSUE=Kidney;
RX PubMed=7649998; DOI=10.1074/jbc.270.34.19861;
RA Davie J.R., Wynn R.M., Meng M., Huang Y.-S., Aalund G., Chuang D.T.,
RA Lau K.S.;
RT "Expression and characterization of branched-chain alpha-ketoacid
RT dehydrogenase kinase from the rat. Is it a histidine-protein kinase?";
RL J. Biol. Chem. 270:19861-19867(1995).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31; SER-356 AND SER-360, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalyzes the phosphorylation and inactivation of the
CC branched-chain alpha-ketoacid dehydrogenase complex, the key regulatory
CC enzyme of the valine, leucine and isoleucine catabolic pathways. Key
CC enzyme that regulate the activity state of the BCKD complex.
CC {ECO:0000269|PubMed:1377677, ECO:0000269|PubMed:7649998}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[3-methyl-2-oxobutanoate dehydrogenase] = ADP +
CC H(+) + O-phospho-L-seryl-[3-methyl-2-oxobutanoate dehydrogenase];
CC Xref=Rhea:RHEA:17301, Rhea:RHEA-COMP:13695, Rhea:RHEA-COMP:13696,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.4;
CC Evidence={ECO:0000269|PubMed:1377677, ECO:0000269|PubMed:7649998};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17302;
CC Evidence={ECO:0000269|PubMed:7649998, ECO:0000305|PubMed:1377677};
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion
CC {ECO:0000250|UniProtKB:O14874}.
CC -!- TISSUE SPECIFICITY: Expressed in heart and liver.
CC {ECO:0000269|PubMed:1377677}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:7649998}.
CC -!- SIMILARITY: Belongs to the PDK/BCKDK protein kinase family.
CC {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; M93271; AAA40818.1; -; mRNA.
DR EMBL; U27456; AAB60498.1; -; mRNA.
DR PIR; A42924; A42924.
DR RefSeq; NP_062117.2; NM_019244.2.
DR PDB; 1GJV; X-ray; 2.70 A; A=31-412.
DR PDB; 1GKX; X-ray; 2.30 A; A=31-412.
DR PDB; 1GKZ; X-ray; 2.20 A; A=31-412.
DR PDB; 3TZ0; X-ray; 2.50 A; A=1-412.
DR PDB; 3TZ2; X-ray; 2.85 A; A=1-412.
DR PDB; 3TZ4; X-ray; 2.25 A; A=1-412.
DR PDB; 3TZ5; X-ray; 2.40 A; A=1-412.
DR PDB; 3VAD; X-ray; 2.60 A; A=1-412.
DR PDB; 4DZY; X-ray; 2.10 A; A=1-412.
DR PDB; 4E00; X-ray; 2.15 A; A=1-412.
DR PDB; 4E01; X-ray; 1.97 A; A=1-412.
DR PDB; 4E02; X-ray; 2.15 A; A=1-412.
DR PDB; 4H7Q; X-ray; 2.10 A; A=1-412.
DR PDB; 4H81; X-ray; 2.05 A; A=1-412.
DR PDB; 4H85; X-ray; 2.10 A; A=1-412.
DR PDBsum; 1GJV; -.
DR PDBsum; 1GKX; -.
DR PDBsum; 1GKZ; -.
DR PDBsum; 3TZ0; -.
DR PDBsum; 3TZ2; -.
DR PDBsum; 3TZ4; -.
DR PDBsum; 3TZ5; -.
DR PDBsum; 3VAD; -.
DR PDBsum; 4DZY; -.
DR PDBsum; 4E00; -.
DR PDBsum; 4E01; -.
DR PDBsum; 4E02; -.
DR PDBsum; 4H7Q; -.
DR PDBsum; 4H81; -.
DR PDBsum; 4H85; -.
DR AlphaFoldDB; Q00972; -.
DR SMR; Q00972; -.
DR BioGRID; 248235; 1.
DR IntAct; Q00972; 4.
DR STRING; 10116.ENSRNOP00000026466; -.
DR iPTMnet; Q00972; -.
DR PhosphoSitePlus; Q00972; -.
DR PaxDb; Q00972; -.
DR PRIDE; Q00972; -.
DR Ensembl; ENSRNOT00000078578; ENSRNOP00000069014; ENSRNOG00000019485.
DR GeneID; 29603; -.
DR KEGG; rno:29603; -.
DR UCSC; RGD:2198; rat.
DR CTD; 10295; -.
DR RGD; 2198; Bckdk.
DR eggNOG; KOG0787; Eukaryota.
DR GeneTree; ENSGT00940000159512; -.
DR InParanoid; Q00972; -.
DR OMA; IHHLALH; -.
DR OrthoDB; 1242599at2759; -.
DR PhylomeDB; Q00972; -.
DR TreeFam; TF331303; -.
DR BRENDA; 2.7.11.4; 5301.
DR Reactome; R-RNO-70895; Branched-chain amino acid catabolism.
DR SABIO-RK; Q00972; -.
DR EvolutionaryTrace; Q00972; -.
DR PRO; PR:Q00972; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000019485; Expressed in pancreas and 19 other tissues.
DR ExpressionAtlas; Q00972; baseline and differential.
DR Genevisible; Q00972; RN.
DR GO; GO:0005947; C:mitochondrial alpha-ketoglutarate dehydrogenase complex; IDA:HGNC-UCL.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0047323; F:[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase activity; IMP:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:HGNC-UCL.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:HGNC-UCL.
DR GO; GO:0004740; F:pyruvate dehydrogenase (acetyl-transferring) kinase activity; IBA:GO_Central.
DR GO; GO:0009083; P:branched-chain amino acid catabolic process; IDA:HGNC-UCL.
DR GO; GO:0006550; P:isoleucine catabolic process; IMP:RGD.
DR GO; GO:0006552; P:leucine catabolic process; IMP:RGD.
DR GO; GO:0016310; P:phosphorylation; IDA:HGNC-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IMP:RGD.
DR GO; GO:0006574; P:valine catabolic process; IMP:RGD.
DR Gene3D; 1.20.140.20; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR036784; AK/P_DHK_N_sf.
DR InterPro; IPR018955; BCDHK/PDK_N.
DR InterPro; IPR039028; BCKD/PDK.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR005467; His_kinase_dom.
DR InterPro; IPR004358; Sig_transdc_His_kin-like_C.
DR PANTHER; PTHR11947; PTHR11947; 1.
DR Pfam; PF10436; BCDHK_Adom3; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR PRINTS; PR00344; BCTRLSENSOR.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR SUPFAM; SSF69012; SSF69012; 1.
DR PROSITE; PS50109; HIS_KIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Direct protein sequencing; Kinase;
KW Mitochondrion; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Transferase; Transit peptide.
FT TRANSIT 1..30
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1377677"
FT CHAIN 31..412
FT /note="[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]]
FT kinase, mitochondrial"
FT /id="PRO_0000023454"
FT DOMAIN 159..404
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:7649998,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 192
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O14874"
FT MOD_RES 233
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O14874"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 110..124
FT /note="RSLPFIIGCNPTILH -> VVFLSSLVATLPYCT (in Ref. 1 and
FT 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="C -> S (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:1GKZ"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:3TZ4"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:4E01"
FT HELIX 85..111
FT /evidence="ECO:0007829|PDB:4E01"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:4E01"
FT HELIX 120..138
FT /evidence="ECO:0007829|PDB:4E01"
FT HELIX 145..161
FT /evidence="ECO:0007829|PDB:4E01"
FT TURN 162..164
FT /evidence="ECO:0007829|PDB:4E01"
FT HELIX 165..176
FT /evidence="ECO:0007829|PDB:4E01"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:4E01"
FT HELIX 184..209
FT /evidence="ECO:0007829|PDB:4E01"
FT STRAND 221..225
FT /evidence="ECO:0007829|PDB:4E01"
FT HELIX 227..246
FT /evidence="ECO:0007829|PDB:4E01"
FT STRAND 252..257
FT /evidence="ECO:0007829|PDB:4E01"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:4E01"
FT HELIX 267..286
FT /evidence="ECO:0007829|PDB:4E01"
FT STRAND 298..304
FT /evidence="ECO:0007829|PDB:4E01"
FT STRAND 306..314
FT /evidence="ECO:0007829|PDB:4E01"
FT HELIX 322..325
FT /evidence="ECO:0007829|PDB:4E01"
FT TURN 326..329
FT /evidence="ECO:0007829|PDB:4E01"
FT HELIX 369..379
FT /evidence="ECO:0007829|PDB:4E01"
FT STRAND 383..389
FT /evidence="ECO:0007829|PDB:4E01"
FT TURN 390..392
FT /evidence="ECO:0007829|PDB:4E01"
FT STRAND 393..401
FT /evidence="ECO:0007829|PDB:4E01"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:1GKZ"
SQ SEQUENCE 412 AA; 46474 MW; D630D3A44728927E CRC64;
MILTSVLGSG PRSGSSLWPL LGSSLSLRVR STSATDTHHV ELARERSKTV TSFYNQSAID
VVAEKPSVRL TPTMMLYSGR SQDGSHLLKS GRYLQQELPV RIAHRIKGFR SLPFIIGCNP
TILHVHELYI RAFQKLTDFP PIKDQADEAQ YCQLVRQLLD DHKDVVTLLA EGLRESRKHI
EDEKLVRYFL DKTLTSRLGI RMLATHHLAL HEDKPDFVGI ICTRLSPKKI IEKWVDFARR
LCEHKYGNAP RVRINGHVAA RFPFIPMPLD YILPELLKNA MRATMESHLD TPYNVPDVVI
TIANNDVDLI IRISDRGGGI AHKDLDRVMD YHFTTAEAST QDPRISPLFG HLDMHSGGQS
GPMHGFGFGL PTSRAYAEYL GGSLQLQSLQ GIGTDVYLRL RHIDGREESF RI
