PDK4_ICTTR
ID PDK4_ICTTR Reviewed; 412 AA.
AC O88345;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial;
DE EC=2.7.11.2;
DE AltName: Full=Pyruvate dehydrogenase kinase isoform 4;
DE Flags: Precursor;
GN Name=PDK4;
OS Ictidomys tridecemlineatus (Thirteen-lined ground squirrel) (Spermophilus
OS tridecemlineatus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Sciuromorpha; Sciuridae;
OC Xerinae; Marmotini; Ictidomys.
OX NCBI_TaxID=43179;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Heart;
RX PubMed=9653197; DOI=10.1073/pnas.95.14.8392;
RA Andrews M.T., Squire T.L., Bowen C.M., Rollins M.B.;
RT "Low-temperature carbon utilization is regulated by novel gene activity in
RT the heart of a hibernating mammal.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8392-8397(1998).
CC -!- FUNCTION: Kinase that plays a key role in regulation of glucose and
CC fatty acid metabolism and homeostasis via phosphorylation of the
CC pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate
CC dehydrogenase activity, and thereby regulates metabolite flux through
CC the tricarboxylic acid cycle, down-regulates aerobic respiration and
CC inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition
CC of pyruvate dehydrogenase decreases glucose utilization and increases
CC fat metabolism in response to prolonged fasting and starvation. Plays
CC an important role in maintaining normal blood glucose levels under
CC starvation, and is involved in the insulin signaling cascade. Via its
CC regulation of pyruvate dehydrogenase activity, plays an important role
CC in maintaining normal blood pH and in preventing the accumulation of
CC ketone bodies under starvation. In the fed state, mediates cellular
CC responses to glucose levels and to a high-fat diet. Regulates both
CC fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role
CC in the generation of reactive oxygen species. Protects detached
CC epithelial cells against anoikis. Plays a role in cell proliferation
CC via its role in regulating carbohydrate and fatty acid metabolism.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[pyruvate dehydrogenase E1 alpha subunit] = ADP
CC + H(+) + O-phospho-L-seryl-[pyruvate dehydrogenase E1 alpha subunit];
CC Xref=Rhea:RHEA:23052, Rhea:RHEA-COMP:13689, Rhea:RHEA-COMP:13690,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.2;
CC -!- SUBUNIT: Homodimer. Interacts with the pyruvate dehydrogenase complex
CC subunit DLAT, and is part of the multimeric pyruvate dehydrogenase
CC complex that contains multiple copies of pyruvate dehydrogenase (E1),
CC dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide
CC dehydrogenase (DLD, E3) (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- TISSUE SPECIFICITY: Detected in skeletal muscle and heart.
CC {ECO:0000269|PubMed:9653197}.
CC -!- INDUCTION: Up-regulated during hibernation.
CC {ECO:0000269|PubMed:9653197}.
CC -!- SIMILARITY: Belongs to the PDK/BCKDK protein kinase family.
CC {ECO:0000305}.
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DR EMBL; AF020845; AAC40161.1; -; mRNA.
DR RefSeq; NP_001269196.1; NM_001282267.1.
DR AlphaFoldDB; O88345; -.
DR SMR; O88345; -.
DR STRING; 43179.ENSSTOP00000019435; -.
DR GeneID; 101976272; -.
DR CTD; 5166; -.
DR eggNOG; KOG0787; Eukaryota.
DR InParanoid; O88345; -.
DR OrthoDB; 1242599at2759; -.
DR Proteomes; UP000005215; Unassembled WGS sequence.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004740; F:pyruvate dehydrogenase (acetyl-transferring) kinase activity; ISS:UniProtKB.
DR GO; GO:0071398; P:cellular response to fatty acid; ISS:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0042750; P:hibernation; IEA:UniProtKB-KW.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; ISS:UniProtKB.
DR GO; GO:0010510; P:regulation of acetyl-CoA biosynthetic process from pyruvate; ISS:UniProtKB.
DR GO; GO:0042304; P:regulation of fatty acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; ISS:UniProtKB.
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 PANTHER; PTHR11947; PTHR11947; 1.
DR Pfam; PF10436; BCDHK_Adom3; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR SUPFAM; SSF69012; SSF69012; 1.
DR PROSITE; PS50109; HIS_KIN; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Carbohydrate metabolism; Glucose metabolism; Hibernation;
KW Kinase; Mitochondrion; Nucleotide-binding; Reference proteome; Transferase;
KW Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..412
FT /note="[Pyruvate dehydrogenase (acetyl-transferring)]
FT kinase isozyme 4, mitochondrial"
FT /id="PRO_0000023448"
FT DOMAIN 138..368
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT BINDING 254..261
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 293
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 312..313
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 329..334
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 157
FT /note="Interaction with the other subunit in the homodimer"
FT /evidence="ECO:0000250"
FT SITE 161
FT /note="Interaction with the other subunit in the homodimer"
FT /evidence="ECO:0000250"
FT SITE 395
FT /note="Interaction with the other subunit in the homodimer"
FT /evidence="ECO:0000250"
SQ SEQUENCE 412 AA; 46837 MW; 4F51628DCBC84DBB CRC64;
MKAARFAMHS ARSLSSVGLV PREVELFSRY SPSPLSMKQL LDFGSDNACE RTSFSFLRQE
LPVRLANILK EIDVLPDRLT NTSSVQLVKS WYIQSLMELV EFHEKSPEDQ KNLSDFVDTL
IKVRNRHHNV VPTMAQGILE YKDTCTVDPV TNQSLQYFLD RFYMNRISTR MLMNQHILIF
SDSQTGNPSH IGSIDPKCDV VAVIQDAFES SKMLCDQYYL TSPELKLTQV NGKFPGQPIH
IVYVPSHLHH MLFELFKNAM RATVERQESW PSLTPVEVIV VLGKEDLTIK ISDRGGGVPL
RITDRLFSYM YSTAPTPVMD NSRNAPLAGF GYGLPISRLY AKYFQGDLNL YSLSGYGTDA
IIYLKALSSE SVEKLPVFNK SAFKHYQMSS EADDWCIPSR EPRNLSKEKM AM
