CPLM-012707

Genbank Nucleotide ID

[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial

Protein Synonyms/Alias

Pyruvate dehydrogenase kinase isoform 4

Homo sapiens (Human)

Position	Peptide	Type	References
38	SPSPLSMKQLLDFGS	ubiquitination	[1]
111	EKSPDDQKALSDFVD	ubiquitination	[1, 2]
122	DFVDTLIKVRNRHHN	ubiquitination	[2]
142	AQGIIEYKDACTVDP	ubiquitination	[1]
226	YLSSPELKLTQVNGK	ubiquitination	[1]
380	EKLPVFNKSAFKHYQ	ubiquitination	[1]
384	VFNKSAFKHYQMSSE	ubiquitination	[1]

[1] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
[2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]

Functional Description

Serine/threonine kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism.

DOMAIN 138 368 Histidine kinase.
NP_BIND 254 261 ATP.
NP_BIND 312 313 ATP.
NP_BIND 329 334 ATP.
BINDING 293 293 ATP.

3D-structure; ATP-binding; Carbohydrate metabolism; Complete proteome; Glucose metabolism; Kinase; Mitochondrion; Nucleotide-binding; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Transit peptide.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005743; C:mitochondrial inner membrane; IEA:Compara.
GO:0005759; C:mitochondrial matrix; TAS:Reactome.
GO:0005524; F:ATP binding; IDA:UniProtKB.
GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
GO:0004740; F:pyruvate dehydrogenase (acetyl-transferring) kinase activity; ISS:UniProtKB.
GO:0071398; P:cellular response to fatty acid; IMP:UniProtKB.
GO:0009267; P:cellular response to starvation; IDA:UniProtKB.
GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
GO:0008286; P:insulin receptor signaling pathway; IMP:UniProtKB.
GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB.
GO:0006090; P:pyruvate metabolic process; TAS:Reactome.
GO:0072593; P:reactive oxygen species metabolic process; IMP:UniProtKB.
GO:0010510; P:regulation of acetyl-CoA biosynthetic process from pyruvate; IMP:UniProtKB.
GO:0042304; P:regulation of fatty acid biosynthetic process; IMP:UniProtKB.
GO:0046320; P:regulation of fatty acid oxidation; ISS:UniProtKB.
GO:0010906; P:regulation of glucose metabolic process; IMP:UniProtKB.
GO:0006885; P:regulation of pH; ISS:UniProtKB.

IPR018955; BCDHK/PDK_N.
IPR003594; HATPase_ATP-bd.
IPR005467; Sig_transdc_His_kinase_core.

PF10436; BCDHK_Adom3
PF02518; HATPase_c