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FLASH GENE

Symbol

PDK1

contributors: mct/npt - updated : 06-02-2015

HGNC name	pyruvate dehydrogenase kinase, isozyme 1
HGNC id	8809

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	2q31.1      Physical location : 173.420.778 - 173.463.860
Synonym name	mitochondrial pyruvate dehydrogenase kinase isoenzyme 1
Synonym symbol(s)	PDHK1
EC.number	2.7.11.2

DNA

TYPE	functioning gene
STRUCTURE	43.08 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002610 11 - 4576 NP_002601 - 436 - 1995 7499431

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       predominantly Digestive mouth       highly Endocrine adrenal gland       highly Visual eye       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

one histidine kinase domain

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	ortholog to murine Pdk1
	ortholog to rattus Pdk1

Homologene

FAMILY

PDK/BCKDK protein kinase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,matrix

basic FUNCTION	phosphorylating PDH and resulting in its inactivation and thus contributing to the regulation of glucose metabolism
	plays an important role in maintaining glycolysis
	activates a group of kinases, including AKT1, p70 ribosomal S6 kinase (S6K), and serum and glucocorticoid-induced protein kinase (SGK), that mediate many of the effects of insulin as well as other agonists
	BNIP3 and PDK1 are involved in two important pathways, cell death and glycolytic, playing critical roles in these pathways in cardiomyocytes after severe hypoxia
	plays an indispensable role in the development of the cardiovascular system
	important regulator of PDH in clonal beta-cells and PDK1 and PDH are important for efficient metabolic coupling
	PDK1 and PDK2 promote meiotic maturation, as their knockdown disturbs the assembly of the meiotic apparatus, without significantly altering ATP content

CELLULAR PROCESS

protein, post translation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

carbohydrate

signaling

glucose metabolism

a component

heterodimerizing with PDK2

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP binding

protein	binding STRAP
	interacts with phosphoinositides through a pleckstrin homology (PH) domain
	PDK1 positively modulates CDC42BPA activity and drives its localization within lamellipodia

cell & other

REGULATION

Other	regulated by HIF1A (HIF regulation has a key role in maintaining lactate production in human cancer)
	regulation by HIF1A (HIF-1-mediated expression of PDK1: a metabolic switch required for cellular adaptation to hypoxia)
	tyrosine phosphorylation enhances PDK1 kinase activity by promoting ATP and pyruvate dehydrogenase complex binding

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   associated with poor prognosis in head and neck squamous cancer constitutional     --low   in patients with Alzheimer disease compared with nondemented patients

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   PDK1 inhibition could serve as a novel therapeutic approach, in multiple myeloma cancer     PDK1 inhibitors should be investigated for antitumour effects

ANIMAL & CELL MODELS